WO2006134611A1 - Compositions of antiulcerative substituted benzimidazoles - Google Patents
Compositions of antiulcerative substituted benzimidazoles Download PDFInfo
- Publication number
- WO2006134611A1 WO2006134611A1 PCT/IN2005/000203 IN2005000203W WO2006134611A1 WO 2006134611 A1 WO2006134611 A1 WO 2006134611A1 IN 2005000203 W IN2005000203 W IN 2005000203W WO 2006134611 A1 WO2006134611 A1 WO 2006134611A1
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- WO
- WIPO (PCT)
- Prior art keywords
- weight
- range
- formulation
- capsule
- sodium
- Prior art date
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- 150000001556 benzimidazoles Chemical class 0.000 title claims abstract description 29
- 230000000767 anti-ulcer Effects 0.000 title claims abstract description 24
- 239000000203 mixture Substances 0.000 title claims description 252
- 239000008188 pellet Substances 0.000 claims abstract description 333
- 239000002775 capsule Substances 0.000 claims abstract description 297
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims abstract description 214
- 229960001778 rabeprazole sodium Drugs 0.000 claims abstract description 119
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims abstract description 108
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims abstract description 107
- 229910000019 calcium carbonate Inorganic materials 0.000 claims abstract description 107
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims abstract description 107
- 229930195725 Mannitol Natural products 0.000 claims abstract description 106
- 239000000594 mannitol Substances 0.000 claims abstract description 106
- 235000010355 mannitol Nutrition 0.000 claims abstract description 106
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims abstract description 104
- 229920002472 Starch Polymers 0.000 claims abstract description 86
- 239000008107 starch Substances 0.000 claims abstract description 86
- 235000019698 starch Nutrition 0.000 claims abstract description 86
- ZGDLVKWIZHHWIR-UHFFFAOYSA-N 4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]morpholine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(N2CCOCC2)N=C1 ZGDLVKWIZHHWIR-UHFFFAOYSA-N 0.000 claims abstract description 68
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims abstract description 67
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims abstract description 66
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims abstract description 66
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims abstract description 53
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims abstract description 53
- 239000003826 tablet Substances 0.000 claims abstract description 26
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 22
- 235000010216 calcium carbonate Nutrition 0.000 claims abstract description 4
- 239000004480 active ingredient Substances 0.000 claims abstract 2
- 238000009472 formulation Methods 0.000 claims description 223
- 229960005019 pantoprazole Drugs 0.000 claims description 169
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 156
- QQQIECGTIMUVDS-UHFFFAOYSA-N N-[[4-[2-(dimethylamino)ethoxy]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=C(OCCN(C)C)C=C1 QQQIECGTIMUVDS-UHFFFAOYSA-N 0.000 claims description 146
- MJIHNNLFOKEZEW-UHFFFAOYSA-N lansoprazole Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=CC=C2N1 MJIHNNLFOKEZEW-UHFFFAOYSA-N 0.000 claims description 137
- 239000007903 gelatin capsule Substances 0.000 claims description 121
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 120
- YPELFRMCRYSPKZ-UHFFFAOYSA-N 4-amino-5-chloro-2-ethoxy-N-({4-[(4-fluorophenyl)methyl]morpholin-2-yl}methyl)benzamide Chemical compound CCOC1=CC(N)=C(Cl)C=C1C(=O)NCC1OCCN(CC=2C=CC(F)=CC=2)C1 YPELFRMCRYSPKZ-UHFFFAOYSA-N 0.000 claims description 104
- 229960004085 mosapride Drugs 0.000 claims description 103
- 229960004770 esomeprazole Drugs 0.000 claims description 100
- SUBDBMMJDZJVOS-DEOSSOPVSA-N esomeprazole Chemical compound C([S@](=O)C1=NC2=CC=C(C=C2N1)OC)C1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-DEOSSOPVSA-N 0.000 claims description 100
- IQPSEEYGBUAQFF-UHFFFAOYSA-N Pantoprazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC=C(OC(F)F)C=C3N=2)=C1OC IQPSEEYGBUAQFF-UHFFFAOYSA-N 0.000 claims description 99
- 239000004615 ingredient Substances 0.000 claims description 97
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 89
- 229960005302 itopride Drugs 0.000 claims description 82
- 238000013268 sustained release Methods 0.000 claims description 79
- 239000012730 sustained-release form Substances 0.000 claims description 79
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 78
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 claims description 75
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 73
- 229960000381 omeprazole Drugs 0.000 claims description 73
- 239000003381 stabilizer Substances 0.000 claims description 69
- FELGMEQIXOGIFQ-CYBMUJFWSA-N (3r)-9-methyl-3-[(2-methylimidazol-1-yl)methyl]-2,3-dihydro-1h-carbazol-4-one Chemical compound CC1=NC=CN1C[C@@H]1C(=O)C(C=2C(=CC=CC=2)N2C)=C2CC1 FELGMEQIXOGIFQ-CYBMUJFWSA-N 0.000 claims description 68
- FGXWKSZFVQUSTL-UHFFFAOYSA-N domperidone Chemical compound C12=CC=CC=C2NC(=O)N1CCCN(CC1)CCC1N1C2=CC=C(Cl)C=C2NC1=O FGXWKSZFVQUSTL-UHFFFAOYSA-N 0.000 claims description 68
- 229960005343 ondansetron Drugs 0.000 claims description 68
- 229960001253 domperidone Drugs 0.000 claims description 67
- 239000000395 magnesium oxide Substances 0.000 claims description 64
- 239000002662 enteric coated tablet Substances 0.000 claims description 63
- YREYEVIYCVEVJK-VWLOTQADSA-N 2-[(s)-[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl]-1h-benzimidazole Chemical compound COCCCOC1=CC=NC(C[S@](=O)C=2NC3=CC=CC=C3N=2)=C1C YREYEVIYCVEVJK-VWLOTQADSA-N 0.000 claims description 59
- 229960003174 lansoprazole Drugs 0.000 claims description 57
- 150000003839 salts Chemical class 0.000 claims description 53
- 229940032147 starch Drugs 0.000 claims description 49
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 48
- MJIHNNLFOKEZEW-VWLOTQADSA-N 2-[(s)-[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylsulfinyl]-1h-benzimidazole Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1C[S@](=O)C1=NC2=CC=CC=C2N1 MJIHNNLFOKEZEW-VWLOTQADSA-N 0.000 claims description 43
- 239000011248 coating agent Substances 0.000 claims description 43
- 238000000576 coating method Methods 0.000 claims description 43
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 41
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 41
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 41
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 41
- 229960004063 propylene glycol Drugs 0.000 claims description 40
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 claims description 38
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol group Chemical group C(CCCCCCCCCCCCCCC)O BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 claims description 38
- 229920006316 polyvinylpyrrolidine Polymers 0.000 claims description 38
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 36
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 23
- 229930006000 Sucrose Natural products 0.000 claims description 23
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 23
- 239000002702 enteric coating Substances 0.000 claims description 23
- 238000009505 enteric coating Methods 0.000 claims description 23
- 239000005720 sucrose Substances 0.000 claims description 23
- -1 (S)-pantoprazole Chemical compound 0.000 claims description 22
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 21
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 21
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 21
- 229960000913 crospovidone Drugs 0.000 claims description 21
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 21
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 21
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 21
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims description 20
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 19
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 19
- 229960000541 cetyl alcohol Drugs 0.000 claims description 19
- 239000008101 lactose Substances 0.000 claims description 19
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 19
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical class CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 18
- 239000004408 titanium dioxide Substances 0.000 claims description 18
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 17
- 229920000053 polysorbate 80 Polymers 0.000 claims description 17
- 239000008186 active pharmaceutical agent Substances 0.000 claims description 15
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 12
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 12
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 12
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 12
- 229940105329 carboxymethylcellulose Drugs 0.000 claims description 12
- YREYEVIYCVEVJK-UHFFFAOYSA-N rabeprazole Chemical compound COCCCOC1=CC=NC(CS(=O)C=2NC3=CC=CC=C3N=2)=C1C YREYEVIYCVEVJK-UHFFFAOYSA-N 0.000 claims description 12
- 239000002552 dosage form Substances 0.000 claims description 11
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 10
- 239000011575 calcium Substances 0.000 claims description 10
- 229910052791 calcium Inorganic materials 0.000 claims description 10
- 229960004157 rabeprazole Drugs 0.000 claims description 10
- ZBFDAUIVDSSISP-UHFFFAOYSA-N 5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methylsulfinyl]-1H-imidazo[4,5-b]pyridine Chemical compound N=1C2=NC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C ZBFDAUIVDSSISP-UHFFFAOYSA-N 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000011230 binding agent Substances 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 239000000463 material Substances 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 229950008375 tenatoprazole Drugs 0.000 claims description 8
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 7
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 7
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 7
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 7
- 239000000843 powder Substances 0.000 claims description 7
- 239000011734 sodium Substances 0.000 claims description 7
- 229910052708 sodium Inorganic materials 0.000 claims description 7
- 235000021355 Stearic acid Nutrition 0.000 claims description 6
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical group CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 6
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 6
- 239000008117 stearic acid Substances 0.000 claims description 6
- 239000000454 talc Substances 0.000 claims description 6
- 229910052623 talc Inorganic materials 0.000 claims description 6
- 229940033134 talc Drugs 0.000 claims description 6
- 235000012222 talc Nutrition 0.000 claims description 6
- 230000000181 anti-adherent effect Effects 0.000 claims description 5
- 239000003911 antiadherent Substances 0.000 claims description 5
- 239000001095 magnesium carbonate Substances 0.000 claims description 5
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims description 5
- 239000004014 plasticizer Substances 0.000 claims description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
- 239000004359 castor oil Substances 0.000 claims description 4
- 235000019438 castor oil Nutrition 0.000 claims description 4
- 239000003086 colorant Substances 0.000 claims description 4
- DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 claims description 4
- MQHNKCZKNAJROC-UHFFFAOYSA-N dipropyl phthalate Chemical compound CCCOC(=O)C1=CC=CC=C1C(=O)OCCC MQHNKCZKNAJROC-UHFFFAOYSA-N 0.000 claims description 4
- GDCRSXZBSIRSFR-UHFFFAOYSA-N ethyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.CCOC(=O)C=C GDCRSXZBSIRSFR-UHFFFAOYSA-N 0.000 claims description 4
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 4
- 239000008187 granular material Substances 0.000 claims description 4
- 239000000391 magnesium silicate Substances 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 claims description 4
- 235000013772 propylene glycol Nutrition 0.000 claims description 4
- 235000015424 sodium Nutrition 0.000 claims description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 3
- FSBVERYRVPGNGG-UHFFFAOYSA-N dimagnesium dioxido-bis[[oxido(oxo)silyl]oxy]silane hydrate Chemical compound O.[Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O FSBVERYRVPGNGG-UHFFFAOYSA-N 0.000 claims description 3
- 239000000945 filler Substances 0.000 claims description 3
- 239000000314 lubricant Substances 0.000 claims description 3
- 239000011777 magnesium Substances 0.000 claims description 3
- 229910052749 magnesium Inorganic materials 0.000 claims description 3
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 claims description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical class O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 claims description 2
- GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 claims description 2
- 229920000623 Cellulose acetate phthalate Polymers 0.000 claims description 2
- MQIUGAXCHLFZKX-UHFFFAOYSA-N Di-n-octyl phthalate Natural products CCCCCCCCOC(=O)C1=CC=CC=C1C(=O)OCCCCCCCC MQIUGAXCHLFZKX-UHFFFAOYSA-N 0.000 claims description 2
- 229920003135 Eudragit® L 100-55 Polymers 0.000 claims description 2
- 229920003138 Eudragit® L 30 D-55 Polymers 0.000 claims description 2
- BJQHLKABXJIVAM-UHFFFAOYSA-N bis(2-ethylhexyl) phthalate Chemical compound CCCCC(CC)COC(=O)C1=CC=CC=C1C(=O)OCC(CC)CCCC BJQHLKABXJIVAM-UHFFFAOYSA-N 0.000 claims description 2
- 229960003563 calcium carbonate Drugs 0.000 claims description 2
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 2
- 239000007894 caplet Substances 0.000 claims description 2
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- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 2
- 229940095079 dicalcium phosphate anhydrous Drugs 0.000 claims description 2
- 229940049654 glyceryl behenate Drugs 0.000 claims description 2
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 claims description 2
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- 229910052919 magnesium silicate Inorganic materials 0.000 claims description 2
- 235000019792 magnesium silicate Nutrition 0.000 claims description 2
- 229960002366 magnesium silicate Drugs 0.000 claims description 2
- 229910000386 magnesium trisilicate Inorganic materials 0.000 claims description 2
- 235000019793 magnesium trisilicate Nutrition 0.000 claims description 2
- 229940099273 magnesium trisilicate Drugs 0.000 claims description 2
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 claims description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical class OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 claims description 2
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- 229960004274 stearic acid Drugs 0.000 claims description 2
- 229940020465 domperidone 10 mg Drugs 0.000 claims 16
- 229940048949 ondansetron 4 mg Drugs 0.000 claims 16
- 239000005995 Aluminium silicate Substances 0.000 claims 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims 1
- 239000005434 MCC/mannitol excipient Substances 0.000 claims 1
- 235000012211 aluminium silicate Nutrition 0.000 claims 1
- PZZYQPZGQPZBDN-UHFFFAOYSA-N aluminium silicate Chemical compound O=[Al]O[Si](=O)O[Al]=O PZZYQPZGQPZBDN-UHFFFAOYSA-N 0.000 claims 1
- 229910000323 aluminium silicate Inorganic materials 0.000 claims 1
- 235000019441 ethanol Nutrition 0.000 claims 1
- 238000012395 formulation development Methods 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims 1
- 229940091250 magnesium supplement Drugs 0.000 claims 1
- ZADYMNAVLSWLEQ-UHFFFAOYSA-N magnesium;oxygen(2-);silicon(4+) Chemical compound [O-2].[O-2].[O-2].[Mg+2].[Si+4] ZADYMNAVLSWLEQ-UHFFFAOYSA-N 0.000 claims 1
- 239000008014 pharmaceutical binder Substances 0.000 claims 1
- 239000008024 pharmaceutical diluent Substances 0.000 claims 1
- 239000000449 pharmaceutical disintegrant Substances 0.000 claims 1
- 239000008023 pharmaceutical filler Substances 0.000 claims 1
- 239000003414 pharmaceutical glidant Substances 0.000 claims 1
- 239000008019 pharmaceutical lubricant Substances 0.000 claims 1
- 239000007916 tablet composition Substances 0.000 claims 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims 1
- KWORUUGOSLYAGD-YPPDDXJESA-N esomeprazole magnesium Chemical compound [Mg+2].C([S@](=O)C=1[N-]C2=CC=C(C=C2N=1)OC)C1=NC=C(C)C(OC)=C1C.C([S@](=O)C=1[N-]C2=CC=C(C=C2N=1)OC)C1=NC=C(C)C(OC)=C1C KWORUUGOSLYAGD-YPPDDXJESA-N 0.000 description 23
- 239000012530 fluid Substances 0.000 description 16
- 229960004793 sucrose Drugs 0.000 description 14
- 239000007864 aqueous solution Substances 0.000 description 11
- 229960001375 lactose Drugs 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 9
- 239000003844 drug implant Substances 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- YNWDKZIIWCEDEE-SNYZSRNZSA-N sodium;5-(difluoromethoxy)-2-[(s)-(3,4-dimethoxypyridin-2-yl)methylsulfinyl]benzimidazol-1-ide Chemical compound [Na+].COC1=CC=NC(C[S@](=O)C=2[N-]C3=CC=C(OC(F)F)C=C3N=2)=C1OC YNWDKZIIWCEDEE-SNYZSRNZSA-N 0.000 description 8
- 239000000654 additive Substances 0.000 description 7
- 229940126409 proton pump inhibitor Drugs 0.000 description 5
- 239000000612 proton pump inhibitor Substances 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 101150018711 AASS gene Proteins 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000003605 opacifier Substances 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 2
- MKBLHFILKIKSQM-UHFFFAOYSA-N 9-methyl-3-[(2-methyl-1h-imidazol-3-ium-3-yl)methyl]-2,3-dihydro-1h-carbazol-4-one;chloride Chemical compound Cl.CC1=NC=CN1CC1C(=O)C(C=2C(=CC=CC=2)N2C)=C2CC1 MKBLHFILKIKSQM-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 229940123603 Dopamine D2 receptor antagonist Drugs 0.000 description 1
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- FELGMEQIXOGIFQ-UHFFFAOYSA-N Ondansetron Chemical compound CC1=NC=CN1CC1C(=O)C(C=2C(=CC=CC=2)N2C)=C2CC1 FELGMEQIXOGIFQ-UHFFFAOYSA-N 0.000 description 1
- 229940062327 aciphex Drugs 0.000 description 1
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
- 239000002579 antinauseant Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000000442 dopamine 2 receptor blocking agent Substances 0.000 description 1
- 239000003210 dopamine receptor blocking agent Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 229960000197 esomeprazole magnesium Drugs 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Inorganic materials [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 1
- 235000013980 iron oxide Nutrition 0.000 description 1
- VBMVTYDPPZVILR-UHFFFAOYSA-N iron(2+);oxygen(2-) Chemical class [O-2].[Fe+2] VBMVTYDPPZVILR-UHFFFAOYSA-N 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940112641 nexium Drugs 0.000 description 1
- 229960000770 ondansetron hydrochloride Drugs 0.000 description 1
- YNWDKZIIWCEDEE-UHFFFAOYSA-N pantoprazole sodium Chemical compound [Na+].COC1=CC=NC(CS(=O)C=2[N-]C3=CC=C(OC(F)F)C=C3N=2)=C1OC YNWDKZIIWCEDEE-UHFFFAOYSA-N 0.000 description 1
- 229960004048 pantoprazole sodium Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229940032668 prevacid Drugs 0.000 description 1
- 229940089505 prilosec Drugs 0.000 description 1
- 229940061276 protonix Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229960004016 sucrose syrup Drugs 0.000 description 1
- 229940072018 zofran Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
- A61K9/2846—Poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5084—Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
Definitions
- the present invention relates to a stable pharmaceutical formulation for hygroscopic antiulcerative substituted benzimidazoles, optionally in combination with other active pharmaceutical ingredients, in the form of pellets, capsules and tablets.
- Rabeprazole chemically, 2-[[[4-(3-methoxypropoxy)-3-methyl-2- pyridinyl]methyl]sulfinyl]-1H-benzimidazole.
- Rabeprazole is a proton pump inhibitor.
- the therapeutic uses of rabeprazole sodium and related compounds, and their preparations were disclosed in U.S. patent No. 5,045,552.
- Rabeprazole sodium is commercially available as 20 mg enteric-coated tablet. It is sold under the name ACIPHEX. Pantoprazole, chemically, 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2- pyridinyl)methyl]sulfinyl]-1H-benzimidazole. Pantoprazole is a proton pump inhibitor. The therapeutic uses of pantoprazole and related compounds, and their preparations were disclosed in U.S. patent No. 4,758,579.
- Pantoprazole available as 20 mg and 40 mg enteric-coated tablets. Injection is available as freeze dried powder containing 40 mg of pantoprazole per vial. It is sold under the name PROTONIX.
- Omeprazole chemically, 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2- pyridinyl)methyl]sulfinyl]-1H-benzimidazole.
- Omeprazole is a proton pump inhibitor.
- the therapeutic uses of omeprazole and related compounds, and their preparations were disclosed in U.S. patent No. 4,255,431.
- Omeprazole is commercially available as 10 mg, 20 mg and 40 mg enteric-coated capsules. It is sold under the name PRILOSEC.
- Esomeprazole magnesium chemically, (T-4)-bis[5-methoxy-2-[(S)-[(4- methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazolato] magnesium.
- Esomeprazole is a proton pump inhibitor. The therapeutic uses of esomeprazole and related compounds, and their preparations were disclosed in U.S. patent No. 4,255,431.
- Esomeprazole magnesium trihydrate is commercially available as 20 mg and 40 mg enteric-coated capsules. It is sold under the name NEXIUM.
- Lansoprazole chemically, 2-[[[3-methyI-4-(2,2,2-trifluoro-ethoxy)-2- pyridinyI]methyl]sulfinyl]-1 H-benzimidazole.
- Lansoprazole is a proton pump inhibitor. The therapeutic uses of lansoprazole and related compounds, and their preparations were disclosed in U.S. patent No. 4,628,098.
- Lansoprazole is commercially available as 15 mg and 30 mg enteric- coated capsules. It is sold under the name PREVACID.
- Ondansetron chemically, 1 ,2,3,9-tetrahydro-9-methyI-3-[(2-methyl-1 H- imidazoI-1-yI)methyl]-4H-carbazol-4-one.
- Ondansetron is a specific serotonin
- Ondansetron hydrochloride is commercially available as 4 mg, 8 mg, and 24 mg tablets and 4 mg and 8 mg disintegrating tablets. It is sold under the name ZOFRAN.
- Domperidone chemically, 5-chloro-1-[1-[3-(2,3-dihydro-2-oxo-1 H- benzimidazol-1-yl)propyl]-4-piperidinyl]-1 ,3-dihydro-2H-benzimidazol-2-one.
- Domperidone is a dopamine antagonist with antinauseant properties. The therapeutic uses of domperidone and related compounds, and their preparations were disclosed in U.S. patent No. 4,066,772.
- Itopride chemically, N-[[4-[2-dimethylamino)ethoxy]phenyl]methyl]-3,4- dimethoxybenzamide. Itopride is a dopamine D2 receptor antagonist.
- the therapeutic uses of itopride and related compounds, and their preparations were disclosed in European Patent No. 306,827.
- Mosapride chemically, ( ⁇ )-4-amino-5-chloro-2-ethoxy-N-[[4-(4- fluorobenzyl)-2-morpholinyl]methyl]benzamide.
- Mosapride is a selective 5-HT 4 receptor agonist.
- the therapeutic uses of mosapride and related compounds, and their preparations were disclosed in U.S. patent No. 4,870,074. All the above-mentioned patents are incorporated by reference.
- the present invention relates to a stable pharmaceutical formulation for hygroscopic antiulcerative substituted benzimidazoles, optionally in combination with other active pharmaceutical ingredients.
- a stable pharmaceutical formulations for hygroscopic antiulcerative substituted benzimidazoles optionally in combination with other active pharmaceutical ingredients, which comprises substituted benzimidazoles; other active pharmaceutical ingredients selected from domperidone, itopride hydrochloride, mosapride citrate and ondansetron; stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide, heavy sodium carbonate, light calcium carbonate, light magnesium carbonate, light magnesium oxide and light sodium carbonate; and mannitol.
- Other additives conventionally used for pharmaceutical formulations may be included in.the present formulation.
- the preferable substituted benzimidazoles are pantoprazole, rabeprazole, omeprazole, lansoprazole, tenatoprazole, esomeprazole, (S)- pantoprazole, (S)-rabeprazole and (S)-lansoprazole; other active pharmaceutical ingredients are domperidone, itopride hydrochloride, mosapride citrate and ondansetron or a salt thereof.
- the particularly preferable stable pharmaceutical formulations for antiulcerative substituted benzimidazoles optionally in combination with other active pharmaceutical ingredients, which comprises substituted benzimidazoles selected from pantoprazole, rabeprazole, omeprazole, lansoprazole, tenatoprazole, esomeprazole, (S)-pantoprazole, (S)-rabeprazole and (S)- Iansoprazole or a salt thereof in the range of 3 to 70% by weight, more preferably 8 to 65% by weight; other active pharmaceutical ingredients selected from domperidone, itopride hydrochloride, mosapride citrate and ondansetron in the range of 10 to 90% by weight, more preferably 20 to 70% by weight; stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide, heavy sodium carbonate, light calcium carbonate, light magnesium carbonate, light magnesium oxide and light sodium carbonate in the range of 0.5 to 90% by weight, more preferably 5 to 60% by weight
- a pharmaceutical formulation for antiulcerative substituted benzimidazoles according to the invention comprises additives, which are conventionally used in dosage forms. These include but are not limited to disintegrants, binders, lubricants, glidants, fillers or diluents, stabilizing agents, seal coating materials, enteric coating materials, plasticizers, anti-adherents, colorants and the. like.
- disintegrants one can particularly mention sodium starch glycolate, starch, croscarmellose sodium, crospovidone, carboxymethylcellulose calcium, carboxymethylcellulose sodium, magnesium aluminum silicate; or a mixture thereof.
- binder one can particularly mention hydroxypropylcellulose, polyvinylpyrrolidone k-30, hydroxypropylcellulose (low-substituted), starch, or a mixture thereof.
- lubricants one can particularly mention stearic acid; or a salt of stearic acid, talc, sodium stearyl fumarate, glyceryl behenate, magnesium silicate, magnesium trisilicate, hydrogenated castor oil; or a mixture thereof.
- glidants one can particularly mention colloidal anhydrous silica, talc; or a mixture thereof.
- fillers one can particularly mention calcium carbonate, dibasic calcium phosphate, lactose, magnesium carbonate, sucrose, starch, magnesium oxide, lactose anhydrous, microcrystalline cellulose, mannitol; or a mixture thereof.
- stabilizing agents one can particularly mention heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide, heavy sodium carbonate, light calcium carbonate, light magnesium carbonate, light magnesium oxide, light sodium carbonate; or a mixtures thereof.
- seal coating materials one can particularly mention hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, polyvinylpyrrolidone derivatives, alginate derivatives, opadry organic; or a mixture thereof.
- enteric coating materials one can particularly mention cellulose acetate phthalate, hydroxypropylmethylcellulose phthalate and methacrylic acid derivatives such as eudragit L 100-55, eudragit L30 D-55, opadry enteric; or a mixture thereof.
- the enteric polymeric composition also contains plasticizer and anti-adherents. Further it may also optionally contain colorants and opacifiers.
- plasticizers one can particularly mention cetyl alcohol, stearyl alcohol or phthalate derivatives such as diethyl phthalate, dipropyl phthalate, dibutyl phthalate, dioctyl phthalate or polyethleneglycol derivatives; or a mixture thereof.
- anti-adherents one can particularly mention talc, starch, stearic acid, hydrogenated castor oil; or a mixture thereof.
- colorants and opacifiers one can particularly mention iron oxides, titanium dioxide; or a mixture thereof.
- Other ingredients antioxidants and solvents conventionally used for pharmaceutical formulations may be included in the present invention.
- a stable pharmaceutical formulations for antiulcerative substituted benzimidazoles optionally in combination with other active pharmaceutical ingredients, which comprises antiulcerative substituted benzimidazoles selected from pantoprazole, rabeprazole, omeprazole, lansoprazole, esomeprazole, tenatoprazole, (S)-pantoprazoIe, (S)-rabeprazole and (S)- lansoprazole or a salt thereof are enteric coated (EC) pellets or tablets; other active pharmaceutical ingredients selected from domperidone, itopride hydrochloride, mosapride citrate and ondansetron are sustained release (SR) pellets or pellets.
- SR sustained release
- a stable pharmaceutical formulations for antiulcerative substituted benzimidazoles which comprises rabeprazole sodium or (S)-rabeprazoIe sodium; stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide, heavy sodium carbonate, light magnesium oxide, light calcium carbonate, light magnesium carbonate and light sodium carbonate; mannitol, starch, polyvinylpyrrolidone s-630, hydroxypropylcellulose or hydroxypropylcellulose (low-substituted); ethanol, mannitol, sodium stearyl fumarate, hydroxypropylmethylcellulose-i ⁇ cps, acryl EZE, opadry organic and opadry enteric.
- the present invention provides a formulation suitable for rabeprazole sodium having therapeutically active strengths: which comprises rabeprazole sodium in the range of 3 to 23% by weight, light magnesium oxide in the range of 0.5 to 2.5% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 25 to 78% by weight, mannitol in the range of 9 to 80% by weight, polyvinylpyrrolidone s-630 in the range of 0.5 to 4% by weight, starch in the range of 0.5 to 2.5% by weight, hydroxypropylcellulose (low- substituted) or hydroxypropylcellulose in the range of 0.5 to 23% by weight, sodium stearyl fumarate in the range of 0.5 to 2.5% by weight, hydroxypropylmethylcellulose-15cps in the range of 2.5 to 15% by weight, acryl EZE in the range of 7 to 28% by weight, opadry organic white in the range of 3 to 10% by weight and opadry enter
- rabeprazole sodium enteric coated tablets comprising rabeprazole sodium in the range of 6 to 14% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 43 to 60% by weight; mannitol in the range of 16 to 21% by weight, polyvinylpyrrolidone s- 630 in the range of 1.5 to 2.5% by weight, starch in the range of 1 to 2% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose in the range of 13 to 17% by weight, sodium stearyl fumarate in the range of 1 to 2% by weight, hydroxypropylmethylcellulose-15cps in the range of 4.5 to 5.5% by weight and acryl EZE in the range
- Rabeprazole sodium enteric coated tablets (10 mg): which comprises rabeprazole sodium is 7.69% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 53.8% by weight; mannitol is 18.5% by weight, polyvinylpyrrolidone s-630 is 1.92% by weight, starch is 1.15% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose is 15.4% by weight, sodium stearyl fumarate is 1.54% by weight, hydroxypropylmethylcellulose-15cps is 5% by weight and acryl EZE is 14.7% by weight, based on the total weight of enteric coated tablets.
- Rabeprazole sodium enteric coated tablets (20 mg): which comprises rabeprazole sodium is 12.5% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 48.8% by weight; mannitol is 18.8% by weight, polyvinylpyrrolidone s-630 is 2.19% by weight, starch is 1.25% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose is 15% by weight, sodium stearyl fumarate is 1.56% by weight, hydroxypropylmethylcellulose-15cps is 5% by weight and acryl EZE is 14.7% by weight, based on the total weight of enteric coated tablets.
- rabeprazole sodium enteric coated pellets which comprises rabeprazole sodium in the range of 6 to 9% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 46 to 58% by weight, light magnesium oxide in the range of 1 to 2% by weight; mannitol in the range of 16 to 77% by weight, polyvinylpyrrolidone s-630 in the. range of 1.5 to 2.5% by weight, starch in the range of 1 to 1.5% by weight, hydroxypropylmethylcellulose-15cps in the range of 6 to 8% by weight, acryl
- rabeprazole sodium enteric coated pellets which comprises rabeprazole sodium enteric coated pellets in the range of 6 to 20% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
- the present invention provides a formulation suitable for (S)- rabeprazole sodium having therapeutically active strengths: which comprises (S)-rabeprazole sodium in the range of 3 to 23% by weight, light magnesium oxide in the range of 0.5 to 2.5% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 25 to 78% by weight, mannitol in the range of 9 to 80% by weight, polyvinylpyrrolidone s-630 in the range of 0.5 to 4% by weight, starch in the range of 0.5 to 2.5% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose in the range of 0.5 to 23% by weight, sodium stearyl fumarate in the range of 0.5 to 2.5% by weight, hydroxypropylmethylcellulose-15cps in the range of 2.5 to 15%.
- acryl EZE in the range of 7 to 28% by weight
- opadry organic white in the range of 3 to 10% by weight
- opadry enteric pink in the range of 7 to 17% by weight,based on the total weight of pharmaceutical dosage form.
- additional excipients may be used.
- Particularly preferred additives heavy magnesium oxide, heavy calcium carbonate, heavy magnesium carbonate, heavy sodium carbonate and mannitol.
- the preferable (S)-rabeprazole sodium enteric coated tablets comprising (S)-rabeprazole sodium in the range of 6 to 14% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 43 to 60% by weight; mannitol in the range of 16 to 21% by weight, polyvinylpyrrolidone s-630 in the range of 1.5 to 2.5% by weight, starch in the range of 1 to 2% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose in the range of 13 to 17% by weight, sodium stearyl fumarate in the range of 1 to 2% by weight, hydroxypropylmethylcellulose- 15cps in the range of 4.5 to 5.5% by weight and acryl EZE in the range of 13 to 17 % by weight, based on the total weight of enteric coated tablets. More preferable enteric-coated tablets formulations are:
- (S)-rabeprazole sodium enteric coated tablets (10 mg): which comprises (S)- rabeprazole sodium is 7.69% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 53.8% by weight; mannitol is 18.5% by weight, polyvinylpyrrolidone s-630 is 1.92% by weight, starch is 1.15% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose is 15.4% by weight, sodium stearyl fumarate is 1.54% by weight, hydroxypropyl methylcellulose-15cps is 5% by weight and acryl EZE is 14.7% by weight, based on the total weight of enteric coated tablets.
- (S)-rabeprazole sodium enteric coated tablets (20mg): which comprises (S)- rabeprazole sodium is 12.5% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 48.8% by weight; mannitol is 18.8% by weight, polyvinylpyrrolidone s-630 is 2.19% by weight, starch is 1.25% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose is 15% by weight, sodium stearyl fumarate is 1.56% by weight, hydroxypropyl methylcellulose-15cps is 5% by weight and acryl EZE is 14.7% by weight, based on the total weight of enteric coated tablets.
- the preferable (S)-rabeprazole sodium enteric coated pellets which comprises (S)-rabeprazoIe sodium in the range of 6 to 9% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of .46 to 58% by weight, light magnesium oxide in the range of 1 to 2% by weight; mannitol in the range of 16 to 77% by weight, polyvinylpyrrolidone s-630 in the range of 1.5 to 2.5% by weight, starch in the range of 1 to 1.5% by weight, hydroxypropylmethylcellulose-i ⁇ cps in the range of 6 to 8% by weight, acryl EZE in the range of 10 to 14% by weight, opadry organic white in the range of
- the preferable (S)-rabeprazole sodium enteric coated pellets which comprises (S)-rabeprazole sodium enteric coated pellets in the range of 6 to 20% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
- a stable pharmaceutical formulations for antiulcerative substituted benzimidazoles which comprises antiulcerative substituted benzimidazoles selected from pantoprazole and (S)-pantoprazole or a salt thereof; stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate; mannitol, starch, polyvinylpyrrolidone-630 or polyvinylpyrrolidone k-30; hydroxypropylcellulose or hydroxypropylcellulose (low-substituted); sodium stearyl fumarate, hydroxypropylmethylcellulose-15cps, acryl EZE, light calcium carbonate, crospovidone, propylene glycol, croscarmellose sodium, sodium Iauryl sulfate, hydroxypropylmethylcellulose E5 and opadry enteric pink.
- the present invention provides a formulation suitable for forming enteric coated tablets or pellets comprising pantoprazole or a salt thereof in the range of 7 to 40% by weight equivalent to pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 19 to 62% by weight, light calcium carbonate in the range of 4 to 11 % by weight; mannitol in the range of
- croscarmellose sodium in the range of 1.5 to 5% by weight
- crospovidone in the range of 1.5 to 5% by weight
- sodium Iauryl sulfate in the range of 0.25 to 1.25% by weight
- polyvinylpyrrolidone s-630 or polyvinylpyrrolidone k-30 in the range of 0.5 to 4% by weight
- starch in the range of 0.5 to 2.5% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose in the range of 7 to 24% by weight
- hydroxypropyl methylcellulose E5 in the range of 4 to 12% by weight
- sodium stearyl fumarate in the range of 0.5 to 2.5% by weight
- propylene glycol in the range of 0.1 to 1.5% by weight
- hydroxypropylmethylcellulose-15cps in the range of 2.5 to 15% by weight
- acryl EZE in the range of 8 to 21% by weight
- opadry enteric pink in the
- pantoprazole enteric coated tablets comprising pantoprazole or a salt thereof in the range of 15 to 32% by weight equivalent to pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 29 to 49% by weight; mannitol in the range of 16 to 21% by weight, polyvinylpyrrolidone s-630 in the range of 1 to 2.5% by weight, starch in the range of 1 to 2% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose in the range of 13 to 17% by weight; sodium stearyl fumarate in the range of 1 to 2% by weight, hydroxypropylmethylcellulose-5cps in the range of 3 to 7% by weight and acryl EZE in the range of 12 to 16% by weight, based on the total weight of enteric coated tablets. More preferable enteric-coated tablets formulations are:
- Pantoprazole enteric coated tablets (20 mg): which comprises pantoprazole or a salt thereof is 17.4% by weight equivalent to pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 44.2% by weight; mannitol is 18.5% by weight, polyvinylpyrrolidone s-630 is 1.92% by weight, starch is 1.15% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropyl cellulose is 15.4% by weight; sodium stearyl fumarate is 1.54% by weight, propylene glycol in the range of 0.5 to 1% by weight, hydroxypropyl methylcellulose-15cps is 5% by weight and acryl EZE is 14% by weight, based on the total weight of enteric coated tablets.
- Pantoprazole enteric coated tablets 40 mg; which comprises pantoprazole or a salt thereof is 28.3% by weight equivalent to pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 33% by weight; mannitol is 18.8% by weight, polyvinylpyrrolidone s-630 is 2.19% by weight, starch is 1.25% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose is 15% by weight; sodium stearyl fumarate is 1.56% by weight, hydroxypropyImethylcellulose-15cps is 5% by weight and acryl EZE is 14% by weight, based on the total weight of enteric coated tablets.
- pantoprazole enteric coated pellets which comprises pantoprazole or a salt thereof in the range of 11 to 15% by weight equivalent to pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide, and heavy sodium carbonate in the range of 33 to 41 % by weight, light calcium carbonate in the range of 6.5 to 8.5% by weight; mannitol in the range of 11 to 52% by weight, polyvinylpyrrolidone s-630 in the range of 1 to 2% by weight or polyvinylpyrrolidone k-30 in the range of 1.5 to 2.5% by weight, starch in the range of 0.5 to 2.5% by weight, croscarmellose sodium in the range of 2.5 to 3.5% by weight, crospovidone in the range of 2.5 to 3.5% by weight, sodium lauryl sulfate in the range of 0.2 to 1 % by weight, hydroxypropylmethylcellulose E5 in the range of 7 to 9% by weight, propylene glycol in the
- pantoprazole enteric coated pellets which comprises pantoprazole enteric-coated pellets are in the range of 10 to 22% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
- the present invention provides a formulation suitable for forming enteric coated tablets or pellets comprising (S)-pantoprazole or a salt thereof in the range of 7 to 40% by weight equivalent to (S)-pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 19 to 62% by weight, light calcium carbonate in the range of 4 to 11% by weight; mannitol in the range of 7 to 70% by weight, croscarmellose sodium in the range of 1.5 to 5% by weight, crospovidone in the range of 1.5 to 5% by weight, sodium lauryl sulfate in the range of 0.25 to 1.25% by weight, polyvinylpyrrolidone s-630 or polyvinylpyrroli
- pantoprazole enteric coated tablets comprising (S)- pantoprazole or a salt thereof in the range of 15 to 32% by weight equivalent to (S)-pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 29 to 49% by weight; mannitol in the range of 16 to 21% by weight, polyvinylpyrrolidone s-630 in the range of 1 to 2.5% by weight, starch in the range of 1 to 2% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose in the range of 13 to 17% by weight; sodium stearyl fumarate in the range of 1 to 2% by weight, hydroxypropylmethylcellulose-5cps in the range of 3 to 7% by weight and acryl EZE in the range of 12 to 16% by weight, based on the total weight of enteric coated tablets. More preferable enteric-coated tablets formulations are:
- (S)-pantoprazole enteric coated tablets (20 mg): which comprises (S)- pantoprazole or a salt thereof is 17.4% by weight equivalent to (S)- pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 44.2% by weight; mannitol is 18.5% by weight, polyvinylpyrrolidone s-630 is 1.92% by weight, starch is 1.15% by weight, hydroxypropylcellulose (low- substituted) or hydroxypropylcellulose is 15.4% by weight; sodium stearyl fumarate is 1.54% by weight, propylene glycol in the range of 0.5 to 1% by weight, hydroxypropylmethylcellulose-15cps is 5% by weight and acryl EZE is 14% by weight, based on the total weight of enteric coated tablets.
- (S)-pantoprazole enteric coated tablets (40mg); which comprises (S)- pantoprazole or a salt thereof is 28.3% by weight equivalent to (S)- pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 33% by weight; mannitol is 18.8% by weight, polyvinylpyrrolidone s-630 is 2.19% by weight, starch is 1.25% by weight, hydroxypropylcellulose (low- substituted) or hydroxypropylcellulose is 15% by weight; sodium stearyl fumarate is 1.56% by weight, hydroxypropylmethylcellulose-15cps is 5% by weight and acryl EZE is 14% by weight, based on the total weight of enteric coated tablets.
- the preferable (S)-pantoprazole enteric coated pellets which comprises (S)-pantoprazole or a salt thereof in the range of 11 to 15% by weight equivalent to (S)-pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide, and heavy sodium carbonate in the range of 33 to 41% by weight, light calcium carbonate in the range of 6.5 to 8.5% by weight; mannitol in the range of 11 to 52% by weight, polyvinylpyrrolidone s-630 in the range of 1 to 2% by weight or polyvinylpyrrolidone k-30 in the range of 1.5 to 2.5% by weight, starch in the range of 0.5 to 2.5% by weight, croscarmellose sodium in the range of 2.5 to 3.5% by weight, crospovidone in the range of 2.5 to 3.5% by weight, sodium lauryl sulfate in the range of 0.2 to 1% by weight, hydroxypropylmethylcellulose E5 in the range of 7 to 9%
- the preferable (S)-pantoprazole enteric coated pellets which comprises (S)-pantoprazole enteric-coated pellets are in the range of 10 to 22% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
- a stable pharmaceutical formulations for antiulcerative substituted benzimidazoles which comprises omeprazole or a salt thereof, disodium hydrogen phosphate, calcium carbonate, lactose, sucrose, methacrylic acid L- 3OD, tween 80, mannitol, polyvinylpyrrolidone k-30 hydroxypropyl methylcellulose E5, propylene glycol, sodium hydroxide, diethyl phthalate, titanium dioxide, cetyl alcohol and purified talc.
- omeprazole enteric coated pellets which comprises omeprazole or a salt thereof in the range of 5 to 15% by weight, more preferably 7 to 10% by weight, e.g.8.47%, disodium hydrogen phosphate in the range of 0.5 to 2% by weight, more preferably 1 to 1.5% by weight, e.g. 1.27%, light calcium carbonate in the range of 2 to 5% by weight, more preferably 3 to 4% by weight, e.g.
- omeprazole enteric coated pellets which comprises omeprazole enteric-coated pellets are in the range of 5 to 15% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
- a stable pharmaceutical formulations for antiulcerative substituted benzimidazoles which comprises esomeprazole or a salt thereof; stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate; mannitol, starch, crospovidone, polyvinylpyr r olidone s-630; or polyvinylpyrrolidone k-30, hydroxypropylcellulose or hydroxypropylcellulose (low-substituted); acryl EZE, croscarmellose sodium, light calcium carbonate, sodium stearyl fumarate, hydroxypropylmethylcellulose-15cps, sodium lauryl sulfate, propylene glycol, hydroxypropylmethylcellulose E5 and opadry enteric pink.
- the present invention provides a formulation suitable for esomeprazole enteric coated tablets or pellets comprising esomeprazole or a salt thereof in the range of 7 to 40% by weight equivalent to esomeprazole, croscarmellose sodium in the range of 1.5 to 4.5% by weight, crospovidone in the range of 1.5 to 4.5% by weight, sodium lauryl sulfate in the range of 0.1 to 1.0% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 20 to 63% by weight, light calcium carbonate in the range of 4 to 11 % by weight; polyvinylpyrrolidone k-30 or polyvinylpyrrolidone s-630 in the range of 0.5 to 4% by weight; hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose in the range of 7 to 24% by weight; mannitol in the range of 9 to 67% by weight, hydroxypropylmethylcellulose E5
- the preferable esomeprazole enteric coated tablets comprising esomeprazole or a salt thereof in the range of 15 to 31% by weight equivalent to esomeprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 30 to 49% by weight; hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose in the range of 14 to 17% by weight; mannitol in the range of 17 to 21% by weight, polyvinylpyrrolidone s-630 in the range of 1.5 to 2.5% by weight, starch in the range of 1 to 1.5% by weight, sodium stearyl fumarate in the range of 1 to 2% by weight, hydroxypropylmethylcellulose- 15cps in the range of 4.5 to 5.5% by weight and acryl EZE in the range of 13 to 16% by weight, based on the total weight of enteric-coated tablets.
- stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate,
- enteric-coated tablet formulations are: i) Esomeprazole enteric coated tablets (20mg): which comprises esomeprazole or a salt thereof is 17.2% by weight equivalent to esomeprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 44.4% by weight; mannitol is 18.5% by weight, polyvinylpyrrolidone s-630 is 1.92% by weight, sodium stearyl fumarate is 1.54% by weight, starch is 1.15% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose is 15.4% by weight; hydroxypropylmethylcellulose-15cps is 5% by weight and acryl EZE is 14% by weight, based on the total weight of enteric coated tablets, ii) Esomeprazole enteric coated tablets (40 mg): which comprises esomeprazole or a salt thereof is 27.9% by weight equivalent to esomeprazole, stabilizers
- the preferable esomeprazole enteric coated pellets which comprises esomeprazole or a salt thereof in the range of 12 to 15% by weight equivalent to esomeprazole, light calcium carbonate in the range of 6.5 to 8.5% by weight, croscarmellose sodium in the range of 2.5 to 3% by weight, crospovidone in the range of 2.5 to 3% by weight, sodium lauryl sulfate in the range of 0.3 to 0.8% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 33 to 41% by weight; mannitol in the range of 20 to 52% by weight, polyvinylpyrrolidone s-630 or polyvinylpyrrolidone k-30 in the range of 1 to 2.5% by weight; starch in the range of 0.5 to 1.5% by weight, hydroxypropylmethylcellulose E5 in the range of 7 to 9% by weight, hydroxypropylmethylcellulose-15cps in the range of 9 to
- a stable pharmaceutical formulations for antiulcerative substituted benzimidazoles which comprises lansoprazole or (S)-Iansoprazole; calcium carboxymethylcellulose, light magnesium carbonate, lactose, sucrose, methacrylic acid L-30D, mannitol, polyvinylpyrrolidone k-30 hydroxypropylmethylcellulose E5, starch, propylene glycol, sodium hydroxide tween 80, diethyl phthalate, titanium dioxide and cetyl alcohol.
- the preferable lansoprazole enteric coated pellets which comprises lansoprazole in the range of 5 to 12% by weight, more preferably 7 to 10% by weight, e.g. 8.47%, light magnesium carbonate in the range of 3 to 10% by weight, more preferably 5.5 to 7.5% by weight, e.g. 6.58%, lactose in the range of 3 to 10% by weight, more preferably 5.5 to 7.5 % by weight, e.g. 6.58%, sucrose in the range of 10 to 24% by weight, more preferably 15 to 19% by weight, e.g. 16.8%, calcium carboxymethylcellulose in the range of 2 to 7% by weight, more preferably 4 to 6 % by weight, e.g.
- mannitol in the range of 5 to 14% by weight, more preferably 8 to 11% by weight, e.g. 9.97%, tween 80. in the range of 0.1 to 0.5% by weight, more preferably 0.1 to 0.4% by weight, e.g. 0.35%, polyvinylpyrrolidone k-30 in the range of 0.1 to 0.5% by weight, more preferably 0.1 to 0.3% by weight, e.g. 0.2%, starch in the range of 4 to 11%by weight, more preferably 6 to 8% by weight, e.g. 7.21%, methacrylic acid L-30D in the range of 14.5 to 35% by weight, more preferably 22 to 28% by weight, e.g.
- hydroxypropylmethylcellulose E5 in the range of 5 to 13% by weight, more preferably 7.5 to 10% by weight, e.g. 8.72%, propylene glycol in the range of 0.2 to 1.5% by weight, more preferably 0.5 to 1% by weight.e.g. 0.81%, sodium hydroxide in the range of 0.05 to 0.25% by weight, more preferably 0.1 to 0.2% by weight,e.g.0.14%, diethyl phthalate in the range of 1 to 3.5% by weight, more preferably 2 to 3% by weight, e.g. 2.49%, titanium dioxide in the range of 0.5 to 2% by weight, more preferably 0.5 to 1.5% by weight, e.g. 0.4% and cetyl alcohol in the range of 0.1 to 1.5% by weight, more preferably 0.5 to 1 % by weight, e.g. 0.75%, based on the total weight of pellets that are filled in hard gelatin capsules.
- the preferable lansoprazole enteric coated pellets which comprises lansoprazole enteric-coated pellets are in the range of 5 to 15% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
- the preferable (S)-Iansoprazole enteric coated pellets which comprises (S)-Iansoprazole in the range of 5 to 12% by weight, more preferably 7 to 10% by weight, e.g. 8.47%, light magnesium carbonate in the range of 3 to 10% by weight, more preferably 5.5. to 7.5% by weight, e.g. 6.58%, lactose in the range of 3 to 10% by weight, more preferably 5.5 to 7.5 % by weight, e.g. 6.58%, sucrose in the range of 10 to 24% by weight, more preferably 15 to 19% by weight, e.g.
- calcium carboxymethylcellulose in the range of 2 to 7% by weight, more preferably 4 to 6 % by weight,e.g. 4.98%, mannitol in the range of 5 to 14% by weight, more preferably 8 to 11% by weight,e.g. 9.97%, tween 80 in the range of 0.1 to 0.5% by weight, more preferably 0.1 to 0.4% by weight,e.g.0.35%, polyvinylpyrrolidone k-30 in the range of 0.1 to 0.5% by weight, more preferably 0.1 to 0.3% by weight.e.g. 0.2%, starch in the range of 4 to 11%by weight, more preferably 6 to 8% by weight, e.g.
- methacrylic acid L-30D in the range of 14.5 to 35% by weight, more preferably 22 to 28% by weight, e.g. 24.9%, hydroxypropylmethylcellulose E5 in the range of 5 to 13% by weight, more preferably 7.5 to 10% by weight, e.g. 8.72%, propylene glycol in the range of 0.2 to 1.5% by weight, more preferably 0.5 to 1% by weight, e.g. 0.81%, sodium hydroxide in the range of 0.05 to 0.25% by weight, more preferably 0.1 to 0.2% by weight, e.g. 0.14%, diethyl phthalate in the range of 1 to 3.5% by weight, more preferably 2 to 3% by weight, e.g.
- titanium dioxide in the range of 0.5 to 2% by weight, more preferably 0.5 to 1.5% by weight, e.g. 0.4% and cetyl alcohol in the range of 0.1 to 1.5% by weight, more preferably 0.5 to 1 % by weight, e.g. 0.75%, based on the total weight of pellets that are filled in hard gelatin capsules.
- the preferable (S)-lansoprazole enteric coated pellets which comprises (S)-lansoprazole enteric-coated pellets are in the range of 5 to 15% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
- the pharmaceutical composition may be for example, in the form of a tablet, a caplet, pellets, a capsule, granules, a pill, powder or a sachet.
- the pharmaceutical composition is in the form of pellets, tablets and capsules.
- the capsule may contain powder, compressed powder, pellets or granules.
- EXAMPLES In the following embodiments of the invention, the below listed quantities of drug substance and additional components are combined using standard pharmaceutical manufacturing techniques. The resulting formulations are used to fill gelatin capsule shells or compressed into tablets.
- Enteric-coated tablet formulation Method of manufacture: The antiulcerative substituted benzimidazole, stabilizer and mannitol are granulated using binder solution of polyvinylpyrrolidone s-630 and starch in planetary mixer, rapid mixer granulator; or other suitable granulator. This wet mass may be then dried in a fluid bed dryer, tray dryer; or other suitable dryer. The dried granulation may be then milled to acheive the desired particle size distribution and then blended with the other ingredients. This blend is compressed into tablets.
- These compressed tablets are seal coated using an aqueous solution of hydroxypropylmethylcellulose-15cps and seal coated tablets are enteric coated using an aqueous dispersion of acryl EZE by using autocota, neocota; or other suitable coating pan.
- Pantoprazole enteric coated (20mg) tablets The components and their amounts were as follows: Pantoprazole enteric coated (20mg) tablets:
- Pantoprazole enteric coated (40mg) tablets The components and their amounts were as follows: Pantoprazole enteric coated (40mg) tablets:
- L-hydroxypropylcellulose (LH-11) 24 15 S Sooddiiuumm sstteeaarryyll ffuummaarraattee 2 2..55 1.56
- the antiulcerative substituted benzimidazole; stabilizer and mannitol are granulated using binder having polyvinylpyrrolidone s-630 and starch in planetary mixer, rapid mixer granulator; or other suitable granulator.
- This wet mass then may be thread like pieces in extruder. Thread like pieces then may be spherical wet pellets in spherodizer. This spherical wet pellets then may be dried in a fluid bed dryer, tray dryer; or other suitable dryer.
- the spherical wet pellets are coated using an aqueous solution of hydroxypropylmethylcellulose in fluid bed coater or other suitable coater.
- the intermediate coated pellets are coated using an aqueous dispersion of acryl EZE in fluid bed coater or other suitable coater.
- the enteric-coated pellets are filled into hard gelatin capsules.
- Rabeprazole sodium enteric-coated pellets The components and their amounts were as follows: Rabeprazole sodium enteric-coated pellets:
- Example 8 The components and their amounts were as follows: Pantoprazole sodium enteric-coated pellets:
- the rabeprazole sodium or (S)- rabeprazole sodium, stabilizer and hydroxypropyl cellulose LF are dissolved in non-aqueous solution.
- the drug solution is loaded on mannitol to get the drug pellets. This drug pellets may be then dried in a fluid bed dryer, tray dryer; or other suitable dryer. B.lntermed ⁇ ate coating
- the drug pellets are coated using non-aqueous solution of opadry oraganic in fluid bed coater; or other suitable coater.
- the intermediate coated pellets are coated using non-aqueous solution of opadry enteric in fluid bed coater; or other suitable coater.
- the enteric-coated pellets are filled into hard gelatin capsules.
- Rabeprazole sodium enteric-coated pellets The components and their amounts were as follows: Rabeprazole sodium enteric-coated pellets:
- pantoprazole (S)- pantoprazole and esomeprazole or a salt thereof:
- pantoprazole, (S)-pantoprazoIe and esomeprazole or a salt thereof, stabilizer, crospovidone, croscarmellose sodium, sodium lauryl sulfate and mannitol are blended.
- Mannitol is wetted using binder having polyvinylpyrrolidone k-30.
- binder having polyvinylpyrrolidone k-30 The above blend is loaded on wet mannitol.
- These drug pellets may be then dried in a fluid bed dryer, tray dryer; or other suitable dryer. B.lntermediate coating
- the drug pellets are coated using non-aqueous solution of hydroxypropylmethyl cellulose E5 and propylene glycol in fluid bed coater; or other suitable coater.
- the intermediate coated pellets are coated using non-aqueous solution of opadry enteric in fluid bed coater; or other suitable coater.
- the enteric-coated pellets are filled into hard gelatin capsules.
- Pantoprazole enteric-coated pellets are Pantoprazole enteric-coated pellets:
- Esomeprazole enteric-coated pellets Ingredients Quantity (mg) %(W/W)
- Enteric-coated pellets formulation Manufacture of omeprazole; or a salt thereof:
- omeprazole or a salt thereof, calcium carbonate, mannitol, sodium lauryl sulfate, lactose, disodium hydrogen phosphate and sucrose are blended.
- Sucrose is wetted using binder having sucrose syrup.
- the above blend is loaded on wet sucrose.
- These drug pellets may be then dried in a fluid bed dryer; tray dryer; or other suitable dryer.
- the drug pellets are coated using aqueous solution of hydroxypropylmethyl cellulose E5, polyvinylpyrrolidone k-30 and propylene glycol in fluid bed coater; or other suitable coater.
- the intermediate coated pellets are coated using aqueous solution of methacrylic acid L-30D, sodium hydroxide, tween 80, diethyl phthalate, titanium dioxide, cetyl alcohol and purified talc in fluid bed coater; or other suitable coater.
- the enteric-coated pellets are filled into hard gelatin capsules.
- Omeprazole enteric-coated pellets are Omeprazole enteric-coated pellets:
- Enteric-coated pellets formulation Manufacture of lansoprazole or (S)-lansoprazole:
- the lansoprazole or (S)-lansoprazole, magnesium carbonate, mannitol, calcium carboxymethylcellulose, lactose, starch and sucrose are blended. Sucrose is wetted using binder. The above blend is loaded on wet sucrose. These drug pellets may be then dried in a fluid bed dryer, tray dryer; or other suitable dryer. B.lntermediate coating
- the drug pellets are coated using aqueous solution of hydroxypropyl methyl cellulose E5, polyvinylpyrrolidone k-30, acetone and propylene glycol in fluid bed coater; or other suitable coater.
- the intermediate coated pellets are coated using aqueous solution of methacrylic acid L-30D, sodium hydroxide, tween 80, diethyl phthalate, titanium dioxide and cetyl alcohol in fluid bed coater; or other suitable coater.
- the enteric-coated pellets are filled into hard gelatin capsules.
- a single dosage unit capsule formulations :
- the antiulcerative substituted benzimidazoles are rabeprazole, pantoprazole, omeprazole, lansoprazole, tenatoprazole, esomeprazole, (S)- pantoprazole, (S)-rabeprazole and (S)-lansoprazole or a salt thereof as enteric coated pellets or tablets and optionally in combination with other active pharmaceutical ingredients are domperidone, itopride hydrochloride, mosapride citrate and ondansetron as sutained release pellets or pellets are filled in required size hard gelatin capsules in various combination of single dosage units.
- Ondansetron (As sustained release pellets) (12%) 100 24.4 Dummy pellets 50 12.2
- Domperidone As sustained release pellets (24%) 125 ' 35.7 Dummy pellets 70 20
- Pantoprazole (20mg)(EC) and ondansetron (4mg) capsules Ingredients Quantity (mg) %(W/W)
- Example 53 Lansoprazole (15mg)(EC) and itopride hydrochloride (50mg) capsules: Ingredients Quantity (mg) %(W/
- Omeprazole (As enteric coated pellets) (8.5%) 236 65.4
- Example 65 Omeprazole (10mg)(EC) and domperidone (10mg) capsules:
- Example 67 Omeprazole (10mg)(EC) and itopride hydrochloride (150mg)(SR) capsules: Ingredients Quantity (mg) %(W/W)
- Omeprazole (As enteric coated pellets) (8.5%) 236 47.1
- Example 71 Omeprazole (10mg)(EC) and mosapride citrate (15mg)(SR) capsules:
- Example 72 Omeprazole (20mg)(EC) and mosapride citrate (15mg)(SR) capsules:
- Example 80 Esomeprazole (40mg)(EC) and domperidone (30mg)(SR) capsules:
- Esomeprazole (40mg)(EC) and domperidone (10mg) capsules Ingredients Quantity (mg) %(W/W)
- Esomeprazole magnesium trihydrate Eq .to esomeprazole (As enteric coated pellets) (13%) 310 68.9
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Abstract
The present invention particularly relates to improved stable pharmaceutical formulations for hygroscopic antiulcerative substituted benzimidazoles, optionally in combination with other active ingredients in the form of pellets, capsules and tablets. For example, stable pharmaceutical formulations of rabeprazole sodium, which comprises rabeprazole sodium, heavy calcium carbonate, mannitol, polyvinylpyrrolidone s-630, starch, hydroxypropylcellulose (low -substituted), sodium stearyl fumarate, hydroxypropylmethylcellulose-15cps and acryl EZE.
Description
COMPOSITIONS OF ANTIULCERATIVE SUBSTITUTED BENZIMIDAZOLES
FIELD OF THE INVENTION
The present invention relates to a stable pharmaceutical formulation for hygroscopic antiulcerative substituted benzimidazoles, optionally in combination with other active pharmaceutical ingredients, in the form of pellets, capsules and tablets.
BACKGROUND OF THE INVENTION
Rabeprazole, chemically, 2-[[[4-(3-methoxypropoxy)-3-methyl-2- pyridinyl]methyl]sulfinyl]-1H-benzimidazole. Rabeprazole is a proton pump inhibitor. The therapeutic uses of rabeprazole sodium and related compounds, and their preparations were disclosed in U.S. patent No. 5,045,552.
Rabeprazole sodium is commercially available as 20 mg enteric-coated tablet. It is sold under the name ACIPHEX. Pantoprazole, chemically, 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2- pyridinyl)methyl]sulfinyl]-1H-benzimidazole. Pantoprazole is a proton pump inhibitor. The therapeutic uses of pantoprazole and related compounds, and their preparations were disclosed in U.S. patent No. 4,758,579.
Pantoprazole available as 20 mg and 40 mg enteric-coated tablets. Injection is available as freeze dried powder containing 40 mg of pantoprazole per vial. It is sold under the name PROTONIX.
Omeprazole, chemically, 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2- pyridinyl)methyl]sulfinyl]-1H-benzimidazole. Omeprazole is a proton pump inhibitor. The therapeutic uses of omeprazole and related compounds, and their preparations were disclosed in U.S. patent No. 4,255,431.
Omeprazole is commercially available as 10 mg, 20 mg and 40 mg enteric-coated capsules. It is sold under the name PRILOSEC.
Esomeprazole magnesium, chemically, (T-4)-bis[5-methoxy-2-[(S)-[(4- methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazolato] magnesium. Esomeprazole is a proton pump inhibitor. The therapeutic uses of esomeprazole and related compounds, and their preparations were disclosed in U.S. patent No. 4,255,431.
Esomeprazole magnesium trihydrate is commercially available as 20 mg and 40 mg enteric-coated capsules. It is sold under the name NEXIUM.
Lansoprazole, chemically, 2-[[[3-methyI-4-(2,2,2-trifluoro-ethoxy)-2- pyridinyI]methyl]sulfinyl]-1 H-benzimidazole. Lansoprazole is a proton pump inhibitor. The therapeutic uses of lansoprazole and related compounds, and their preparations were disclosed in U.S. patent No. 4,628,098. Lansoprazole is commercially available as 15 mg and 30 mg enteric- coated capsules. It is sold under the name PREVACID.
Ondansetron, chemically, 1 ,2,3,9-tetrahydro-9-methyI-3-[(2-methyl-1 H- imidazoI-1-yI)methyl]-4H-carbazol-4-one. Ondansetron is a specific serotonin
(5HT3) receptor antagonist. The therapeutic uses of ondansetron and related compounds, and their preparations were disclosed in U.S. patent No.
4,695,578.
Ondansetron hydrochloride is commercially available as 4 mg, 8 mg, and 24 mg tablets and 4 mg and 8 mg disintegrating tablets. It is sold under the name ZOFRAN. Domperidone, chemically, 5-chloro-1-[1-[3-(2,3-dihydro-2-oxo-1 H- benzimidazol-1-yl)propyl]-4-piperidinyl]-1 ,3-dihydro-2H-benzimidazol-2-one. Domperidone is a dopamine antagonist with antinauseant properties. The therapeutic uses of domperidone and related compounds, and their preparations were disclosed in U.S. patent No. 4,066,772. Itopride, chemically, N-[[4-[2-dimethylamino)ethoxy]phenyl]methyl]-3,4- dimethoxybenzamide. Itopride is a dopamine D2 receptor antagonist. The therapeutic uses of itopride and related compounds, and their preparations were disclosed in European Patent No. 306,827.
Mosapride, chemically, (±)-4-amino-5-chloro-2-ethoxy-N-[[4-(4- fluorobenzyl)-2-morpholinyl]methyl]benzamide. Mosapride is a selective 5-HT4 receptor agonist. The therapeutic uses of mosapride and related compounds, and their preparations were disclosed in U.S. patent No. 4,870,074. All the above-mentioned patents are incorporated by reference.
DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a stable pharmaceutical formulation for hygroscopic antiulcerative substituted benzimidazoles, optionally in combination with other active pharmaceutical ingredients.
According to the present invention, a stable pharmaceutical formulations for hygroscopic antiulcerative substituted benzimidazoles,
optionally in combination with other active pharmaceutical ingredients, which comprises substituted benzimidazoles; other active pharmaceutical ingredients selected from domperidone, itopride hydrochloride, mosapride citrate and ondansetron; stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide, heavy sodium carbonate, light calcium carbonate, light magnesium carbonate, light magnesium oxide and light sodium carbonate; and mannitol. Other additives conventionally used for pharmaceutical formulations may be included in.the present formulation.
The preferable substituted benzimidazoles are pantoprazole, rabeprazole, omeprazole, lansoprazole, tenatoprazole, esomeprazole, (S)- pantoprazole, (S)-rabeprazole and (S)-lansoprazole; other active pharmaceutical ingredients are domperidone, itopride hydrochloride, mosapride citrate and ondansetron or a salt thereof.
The particularly preferable stable pharmaceutical formulations for antiulcerative substituted benzimidazoles, optionally in combination with other active pharmaceutical ingredients, which comprises substituted benzimidazoles selected from pantoprazole, rabeprazole, omeprazole, lansoprazole, tenatoprazole, esomeprazole, (S)-pantoprazole, (S)-rabeprazole and (S)- Iansoprazole or a salt thereof in the range of 3 to 70% by weight, more preferably 8 to 65% by weight; other active pharmaceutical ingredients selected from domperidone, itopride hydrochloride, mosapride citrate and ondansetron in the range of 10 to 90% by weight, more preferably 20 to 70% by weight; stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide, heavy sodium carbonate, light calcium carbonate, light magnesium carbonate, light magnesium oxide and light sodium carbonate in the range of 0.5 to 90% by weight, more preferably 5 to 60% by weight and mannitol in the range of 9 to 80% by weight, more preferably 15 to 75% by weight, based on the total weight of pharmaceutical formulations.
A pharmaceutical formulation for antiulcerative substituted benzimidazoles according to the invention comprises additives, which are conventionally used in dosage forms. These include but are not limited to disintegrants, binders, lubricants, glidants, fillers or diluents, stabilizing agents, seal coating materials, enteric coating materials, plasticizers, anti-adherents, colorants and the. like.
As disintegrants one can particularly mention sodium starch glycolate, starch, croscarmellose sodium, crospovidone, carboxymethylcellulose calcium, carboxymethylcellulose sodium, magnesium aluminum silicate; or a mixture thereof. As binder one can particularly mention hydroxypropylcellulose, polyvinylpyrrolidone k-30, hydroxypropylcellulose (low-substituted), starch, or a mixture thereof. As lubricants one can particularly mention stearic acid; or a salt of stearic acid, talc, sodium stearyl fumarate, glyceryl behenate, magnesium silicate, magnesium trisilicate, hydrogenated castor oil; or a mixture thereof. As glidants one can particularly mention colloidal anhydrous silica, talc; or a mixture thereof. As fillers one can particularly mention calcium carbonate, dibasic calcium phosphate, lactose, magnesium carbonate, sucrose, starch, magnesium oxide, lactose anhydrous, microcrystalline cellulose, mannitol; or a mixture thereof. As stabilizing agents one can particularly mention heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide, heavy sodium carbonate, light calcium carbonate, light magnesium carbonate, light magnesium oxide, light sodium carbonate; or a mixtures thereof. As seal coating materials one can particularly mention hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, polyvinylpyrrolidone derivatives, alginate derivatives, opadry organic; or a mixture thereof. As enteric coating materials one can particularly mention cellulose acetate phthalate, hydroxypropylmethylcellulose phthalate and methacrylic acid derivatives such as eudragit L 100-55, eudragit L30 D-55, opadry enteric; or a mixture thereof. The enteric polymeric composition also contains plasticizer and anti-adherents. Further it may also optionally contain colorants and opacifiers. As plasticizers one can particularly mention cetyl alcohol, stearyl alcohol or phthalate derivatives such as diethyl phthalate, dipropyl phthalate, dibutyl phthalate, dioctyl phthalate or polyethleneglycol derivatives; or a mixture thereof. As anti-adherents one can particularly mention talc, starch, stearic acid, hydrogenated castor oil; or a mixture thereof. As colorants and opacifiers one can particularly mention iron oxides, titanium dioxide; or a mixture thereof. Other ingredients antioxidants and solvents conventionally used for pharmaceutical formulations may be included in the present invention.
A stable pharmaceutical formulations for antiulcerative substituted benzimidazoles, optionally in combination with other active pharmaceutical
ingredients, which comprises antiulcerative substituted benzimidazoles selected from pantoprazole, rabeprazole, omeprazole, lansoprazole, esomeprazole, tenatoprazole, (S)-pantoprazoIe, (S)-rabeprazole and (S)- lansoprazole or a salt thereof are enteric coated (EC) pellets or tablets; other active pharmaceutical ingredients selected from domperidone, itopride hydrochloride, mosapride citrate and ondansetron are sustained release (SR) pellets or pellets.
A stable pharmaceutical formulations for antiulcerative substituted benzimidazoles, which comprises rabeprazole sodium or (S)-rabeprazoIe sodium; stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide, heavy sodium carbonate, light magnesium oxide, light calcium carbonate, light magnesium carbonate and light sodium carbonate; mannitol, starch, polyvinylpyrrolidone s-630, hydroxypropylcellulose or hydroxypropylcellulose (low-substituted); ethanol, mannitol, sodium stearyl fumarate, hydroxypropylmethylcellulose-iδcps, acryl EZE, opadry organic and opadry enteric.
The present invention provides a formulation suitable for rabeprazole sodium having therapeutically active strengths: which comprises rabeprazole sodium in the range of 3 to 23% by weight, light magnesium oxide in the range of 0.5 to 2.5% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 25 to 78% by weight, mannitol in the range of 9 to 80% by weight, polyvinylpyrrolidone s-630 in the range of 0.5 to 4% by weight, starch in the range of 0.5 to 2.5% by weight, hydroxypropylcellulose (low- substituted) or hydroxypropylcellulose in the range of 0.5 to 23% by weight, sodium stearyl fumarate in the range of 0.5 to 2.5% by weight, hydroxypropylmethylcellulose-15cps in the range of 2.5 to 15% by weight, acryl EZE in the range of 7 to 28% by weight, opadry organic white in the range of 3 to 10% by weight and opadry enteric pink in the range of 7 to 17% by weight, based on the total weight of pharmaceutical dosage form. Optionally additional excipients may be used. Particularly preferred additives heavy magnesium oxide, heavy calcium carbonate, heavy magnesium carbonate, heavy sodium carbonate and mannitol, based on the total weight of pharmaceutical formulations.
The preferable rabeprazole sodium enteric coated tablets comprising rabeprazole sodium in the range of 6 to 14% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 43 to 60% by weight; mannitol in the range of 16 to 21% by weight, polyvinylpyrrolidone s- 630 in the range of 1.5 to 2.5% by weight, starch in the range of 1 to 2% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose in the range of 13 to 17% by weight, sodium stearyl fumarate in the range of 1 to 2% by weight, hydroxypropylmethylcellulose-15cps in the range of 4.5 to 5.5% by weight and acryl EZE in the range of 13 to 17 % by weight, based on the total weight of enteric coated tablets. More preferable enteric-coated tablets formulations are:
i) Rabeprazole sodium enteric coated tablets (10 mg): which comprises rabeprazole sodium is 7.69% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 53.8% by weight; mannitol is 18.5% by weight, polyvinylpyrrolidone s-630 is 1.92% by weight, starch is 1.15% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose is 15.4% by weight, sodium stearyl fumarate is 1.54% by weight, hydroxypropylmethylcellulose-15cps is 5% by weight and acryl EZE is 14.7% by weight, based on the total weight of enteric coated tablets.
ii) Rabeprazole sodium enteric coated tablets (20 mg): which comprises rabeprazole sodium is 12.5% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 48.8% by weight; mannitol is 18.8% by weight, polyvinylpyrrolidone s-630 is 2.19% by weight, starch is 1.25% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose is 15% by weight, sodium stearyl fumarate is 1.56% by weight, hydroxypropylmethylcellulose-15cps is 5% by weight and acryl EZE is 14.7% by weight, based on the total weight of enteric coated tablets.
The preferable rabeprazole sodium enteric coated pellets: which comprises rabeprazole sodium in the range of 6 to 9% by weight, stabilizers
selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 46 to 58% by weight, light magnesium oxide in the range of 1 to 2% by weight; mannitol in the range of 16 to 77% by weight, polyvinylpyrrolidone s-630 in the. range of 1.5 to 2.5% by weight, starch in the range of 1 to 1.5% by weight, hydroxypropylmethylcellulose-15cps in the range of 6 to 8% by weight, acryl
EZE in the range of 10 to 14% by weight, opadry organic white in the range of 6 to 8% by weight and opadry enteric pink in the range of 10 to 14% by weight, based on the total weight of pellets that are filled in hard gelatin capsules. The preferable rabeprazole sodium enteric coated pellets: which comprises rabeprazole sodium enteric coated pellets in the range of 6 to 20% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
The present invention provides a formulation suitable for (S)- rabeprazole sodium having therapeutically active strengths: which comprises (S)-rabeprazole sodium in the range of 3 to 23% by weight, light magnesium oxide in the range of 0.5 to 2.5% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 25 to 78% by weight, mannitol in the range of 9 to 80% by weight, polyvinylpyrrolidone s-630 in the range of 0.5 to 4% by weight, starch in the range of 0.5 to 2.5% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose in the range of 0.5 to 23% by weight, sodium stearyl fumarate in the range of 0.5 to 2.5% by weight, hydroxypropylmethylcellulose-15cps in the range of 2.5 to 15%. by weight, acryl EZE in the range of 7 to 28% by weight, opadry organic white in the range of 3 to 10% by weight and opadry enteric pink in the range of 7 to 17% by weight,based on the total weight of pharmaceutical dosage form. Optionally additional excipients may be used. Particularly preferred additives heavy magnesium oxide, heavy calcium carbonate, heavy magnesium carbonate, heavy sodium carbonate and mannitol.
The preferable (S)-rabeprazole sodium enteric coated tablets comprising (S)-rabeprazole sodium in the range of 6 to 14% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range
of 43 to 60% by weight; mannitol in the range of 16 to 21% by weight, polyvinylpyrrolidone s-630 in the range of 1.5 to 2.5% by weight, starch in the range of 1 to 2% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose in the range of 13 to 17% by weight, sodium stearyl fumarate in the range of 1 to 2% by weight, hydroxypropylmethylcellulose- 15cps in the range of 4.5 to 5.5% by weight and acryl EZE in the range of 13 to 17 % by weight, based on the total weight of enteric coated tablets. More preferable enteric-coated tablets formulations are:
i) (S)-rabeprazole sodium enteric coated tablets (10 mg): which comprises (S)- rabeprazole sodium is 7.69% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 53.8% by weight; mannitol is 18.5% by weight, polyvinylpyrrolidone s-630 is 1.92% by weight, starch is 1.15% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose is 15.4% by weight, sodium stearyl fumarate is 1.54% by weight, hydroxypropyl methylcellulose-15cps is 5% by weight and acryl EZE is 14.7% by weight, based on the total weight of enteric coated tablets.
ii) (S)-rabeprazole sodium enteric coated tablets (20mg): which comprises (S)- rabeprazole sodium is 12.5% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 48.8% by weight; mannitol is 18.8% by weight, polyvinylpyrrolidone s-630 is 2.19% by weight, starch is 1.25% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose is 15% by weight, sodium stearyl fumarate is 1.56% by weight, hydroxypropyl methylcellulose-15cps is 5% by weight and acryl EZE is 14.7% by weight, based on the total weight of enteric coated tablets.
The preferable (S)-rabeprazole sodium enteric coated pellets: which comprises (S)-rabeprazoIe sodium in the range of 6 to 9% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of .46 to 58% by weight, light magnesium oxide in the range of 1 to 2% by weight; mannitol in the range of 16 to 77% by weight, polyvinylpyrrolidone s-630 in the range of 1.5
to 2.5% by weight, starch in the range of 1 to 1.5% by weight, hydroxypropylmethylcellulose-iδcps in the range of 6 to 8% by weight, acryl EZE in the range of 10 to 14% by weight, opadry organic white in the range of
6 to 8% by weight and opadry enteric pink in the range of 10 to 14% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
The preferable (S)-rabeprazole sodium enteric coated pellets: which comprises (S)-rabeprazole sodium enteric coated pellets in the range of 6 to 20% by weight, based on the total weight of pellets that are filled in hard gelatin capsules. A stable pharmaceutical formulations for antiulcerative substituted benzimidazoles, which comprises antiulcerative substituted benzimidazoles selected from pantoprazole and (S)-pantoprazole or a salt thereof; stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate; mannitol, starch, polyvinylpyrrolidone-630 or polyvinylpyrrolidone k-30; hydroxypropylcellulose or hydroxypropylcellulose (low-substituted); sodium stearyl fumarate, hydroxypropylmethylcellulose-15cps, acryl EZE, light calcium carbonate, crospovidone, propylene glycol, croscarmellose sodium, sodium Iauryl sulfate, hydroxypropylmethylcellulose E5 and opadry enteric pink. The present invention provides a formulation suitable for forming enteric coated tablets or pellets comprising pantoprazole or a salt thereof in the range of 7 to 40% by weight equivalent to pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 19 to 62% by weight, light calcium carbonate in the range of 4 to 11 % by weight; mannitol in the range of
7 to 70% by weight, croscarmellose sodium in the range of 1.5 to 5% by weight, crospovidone in the range of 1.5 to 5% by weight, sodium Iauryl sulfate in the range of 0.25 to 1.25% by weight, polyvinylpyrrolidone s-630 or polyvinylpyrrolidone k-30 in the range of 0.5 to 4% by weight; starch in the range of 0.5 to 2.5% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose in the range of 7 to 24% by weight; hydroxypropyl methylcellulose E5 in the range of 4 to 12% by weight, sodium stearyl fumarate in the range of 0.5 to 2.5% by weight, propylene glycol in the range of 0.1 to 1.5% by weight, hydroxypropylmethylcellulose-15cps in the range of
2.5 to 15% by weight, acryl EZE in the range of 8 to 21% by weight and opadry enteric pink in the range of 9 to 21% by weight, based on the total weight of pharmaceutical dosage form. Optionally additional excipients may be used. Particularly preferred additives heavy magnesium oxide, heavy calcium carbonate, heavy magnesium carbonate, heavy sodium carbonate and mannitol.
The preferable pantoprazole enteric coated tablets comprising pantoprazole or a salt thereof in the range of 15 to 32% by weight equivalent to pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 29 to 49% by weight; mannitol in the range of 16 to 21% by weight, polyvinylpyrrolidone s-630 in the range of 1 to 2.5% by weight, starch in the range of 1 to 2% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose in the range of 13 to 17% by weight; sodium stearyl fumarate in the range of 1 to 2% by weight, hydroxypropylmethylcellulose-5cps in the range of 3 to 7% by weight and acryl EZE in the range of 12 to 16% by weight, based on the total weight of enteric coated tablets. More preferable enteric-coated tablets formulations are:
i) Pantoprazole enteric coated tablets (20 mg): which comprises pantoprazole or a salt thereof is 17.4% by weight equivalent to pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 44.2% by weight; mannitol is 18.5% by weight, polyvinylpyrrolidone s-630 is 1.92% by weight, starch is 1.15% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropyl cellulose is 15.4% by weight; sodium stearyl fumarate is 1.54% by weight, propylene glycol in the range of 0.5 to 1% by weight, hydroxypropyl methylcellulose-15cps is 5% by weight and acryl EZE is 14% by weight, based on the total weight of enteric coated tablets.
ii) Pantoprazole enteric coated tablets (40 mg); which comprises pantoprazole or a salt thereof is 28.3% by weight equivalent to pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 33% by weight; mannitol is
18.8% by weight, polyvinylpyrrolidone s-630 is 2.19% by weight, starch is 1.25% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose is 15% by weight; sodium stearyl fumarate is 1.56% by weight, hydroxypropyImethylcellulose-15cps is 5% by weight and acryl EZE is 14% by weight, based on the total weight of enteric coated tablets.
The preferable pantoprazole enteric coated pellets: which comprises pantoprazole or a salt thereof in the range of 11 to 15% by weight equivalent to pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide, and heavy sodium carbonate in the range of 33 to 41 % by weight, light calcium carbonate in the range of 6.5 to 8.5% by weight; mannitol in the range of 11 to 52% by weight, polyvinylpyrrolidone s-630 in the range of 1 to 2% by weight or polyvinylpyrrolidone k-30 in the range of 1.5 to 2.5% by weight, starch in the range of 0.5 to 2.5% by weight, croscarmellose sodium in the range of 2.5 to 3.5% by weight, crospovidone in the range of 2.5 to 3.5% by weight, sodium lauryl sulfate in the range of 0.2 to 1 % by weight, hydroxypropylmethylcellulose E5 in the range of 7 to 9% by weight, propylene glycol in the range of 0.5 to 1% by weight, hydroxypropylmethylcellulose-15cps in the range of 9 to 11% by weight, acryl EZE in the range of 13.5 to 16.5% by weight and opadry enteric pink in the range of 13.5 to 16.5% by weight,based on the total weight of pellets that are filled in hard gelatin capsules.
The preferable pantoprazole enteric coated pellets; which comprises pantoprazole enteric-coated pellets are in the range of 10 to 22% by weight, based on the total weight of pellets that are filled in hard gelatin capsules. The present invention provides a formulation suitable for forming enteric coated tablets or pellets comprising (S)-pantoprazole or a salt thereof in the range of 7 to 40% by weight equivalent to (S)-pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 19 to 62% by weight, light calcium carbonate in the range of 4 to 11% by weight; mannitol in the range of 7 to 70% by weight, croscarmellose sodium in the range of 1.5 to 5% by weight, crospovidone in the range of 1.5 to 5% by weight, sodium lauryl sulfate in the range of 0.25 to 1.25% by weight, polyvinylpyrrolidone s-630 or polyvinylpyrrolidone k-30 in the range of 0.5 to 4% by weight; starch in the
range of 0.5 to 2.5% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose in the range of 7 to 24% by weight; hydroxypropylmethylcellulose E5 in the range of 4 to 12% by weight, sodium stearyl fumarate in the range of 0.5 to 2.5% by weight, propylene glycol in the range of 0.1 to 1.5% by weight, hydroxypropylmethylcellulose-15cps in the range of 2.5 to 15% by weight, acryl EZE in the range of 8 to 21% by weight and opadry enteric pink in the range of 9 to 21% by weight, based on the total weight of pharmaceutical dosage form. Optionally additional excipients may be used. Particularly preferred additives heavy magnesium oxide, heavy calcium carbonate, heavy magnesium carbonate, heavy sodium carbonate and mannitol.
The preferable pantoprazole enteric coated tablets comprising (S)- pantoprazole or a salt thereof in the range of 15 to 32% by weight equivalent to (S)-pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 29 to 49% by weight; mannitol in the range of 16 to 21% by weight, polyvinylpyrrolidone s-630 in the range of 1 to 2.5% by weight, starch in the range of 1 to 2% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose in the range of 13 to 17% by weight; sodium stearyl fumarate in the range of 1 to 2% by weight, hydroxypropylmethylcellulose-5cps in the range of 3 to 7% by weight and acryl EZE in the range of 12 to 16% by weight, based on the total weight of enteric coated tablets. More preferable enteric-coated tablets formulations are:
i) (S)-pantoprazole enteric coated tablets (20 mg): which comprises (S)- pantoprazole or a salt thereof is 17.4% by weight equivalent to (S)- pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 44.2% by weight; mannitol is 18.5% by weight, polyvinylpyrrolidone s-630 is 1.92% by weight, starch is 1.15% by weight, hydroxypropylcellulose (low- substituted) or hydroxypropylcellulose is 15.4% by weight; sodium stearyl fumarate is 1.54% by weight, propylene glycol in the range of 0.5 to 1% by weight, hydroxypropylmethylcellulose-15cps is 5% by weight and acryl EZE is 14% by weight, based on the total weight of enteric coated tablets.
ii) (S)-pantoprazole enteric coated tablets (40mg); which comprises (S)- pantoprazole or a salt thereof is 28.3% by weight equivalent to (S)- pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 33% by weight; mannitol is 18.8% by weight, polyvinylpyrrolidone s-630 is 2.19% by weight, starch is 1.25% by weight, hydroxypropylcellulose (low- substituted) or hydroxypropylcellulose is 15% by weight; sodium stearyl fumarate is 1.56% by weight, hydroxypropylmethylcellulose-15cps is 5% by weight and acryl EZE is 14% by weight, based on the total weight of enteric coated tablets.
The preferable (S)-pantoprazole enteric coated pellets: which comprises (S)-pantoprazole or a salt thereof in the range of 11 to 15% by weight equivalent to (S)-pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide, and heavy sodium carbonate in the range of 33 to 41% by weight, light calcium carbonate in the range of 6.5 to 8.5% by weight; mannitol in the range of 11 to 52% by weight, polyvinylpyrrolidone s-630 in the range of 1 to 2% by weight or polyvinylpyrrolidone k-30 in the range of 1.5 to 2.5% by weight, starch in the range of 0.5 to 2.5% by weight, croscarmellose sodium in the range of 2.5 to 3.5% by weight, crospovidone in the range of 2.5 to 3.5% by weight, sodium lauryl sulfate in the range of 0.2 to 1% by weight, hydroxypropylmethylcellulose E5 in the range of 7 to 9% by weight, propylene glycol in the range of 0.5 to 1% by weight, hydroxypropylmethylcellulose-15cps in the range of 9 to 11% by weight, acryl EZE in the range of 13.5 to 16.5% by weight and opadry enteric pink in the range of 13.5 to 16.5% by weight,based on the total weight of pellets that are filled in hard gelatin capsules.
The preferable (S)-pantoprazole enteric coated pellets: which comprises (S)-pantoprazole enteric-coated pellets are in the range of 10 to 22% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
A stable pharmaceutical formulations for antiulcerative substituted benzimidazoles, which comprises omeprazole or a salt thereof, disodium hydrogen phosphate, calcium carbonate, lactose, sucrose, methacrylic acid L- 3OD, tween 80, mannitol, polyvinylpyrrolidone k-30 hydroxypropyl
methylcellulose E5, propylene glycol, sodium hydroxide, diethyl phthalate, titanium dioxide, cetyl alcohol and purified talc.
The preferable omeprazole enteric coated pellets: which comprises omeprazole or a salt thereof in the range of 5 to 15% by weight, more preferably 7 to 10% by weight, e.g.8.47%, disodium hydrogen phosphate in the range of 0.5 to 2% by weight, more preferably 1 to 1.5% by weight, e.g. 1.27%, light calcium carbonate in the range of 2 to 5% by weight, more preferably 3 to 4% by weight, e.g. 3.39%, lactose in the range of 2 to 5% by weight, more preferably 3 to 4% by weight, e.g.3.39%, sucrose in the range of 16 to 39% by weight, more preferably 25 to 31% by weight,e.g.27.54%, mannitol in the range of 10 to 24% by weight, more preferably 15 to 19% by weight, e.g.17%, polyvinylpyrrolidone k-30 in the range of 0.1 to 0.5% by weight, more preferably 0.1 to 0.3% by weight, e.g.0.25%, hydroxypropylmethylcellulose E5 in the range of 5 to 13% by weight, more preferably 7 to 10% by weight, e.g.8.76%, propylene glycol in the range of 0.5 to 2% by weight, more preferably 0.5 to 1% by weight, e.g.0.85%, sodium hydroxide in the range of 0.05 to 0.1% by weight, more preferably 0.05 to 0.5% by weight, e.g.0.15%, tween 80 in the range of 0.1 to 0.5% by weight, more preferably 0.2 to 0.3% by weight, e.g.0.254%, diethyl phthalate in the range of 1.5 to 3.5% by weight, more preferably 2 to 3% by weight, e.g.2.5%, titanium dioxide in the range of 0.01 to 0.1% by weight, more preferably 0.02 to 0.06% by weight, e.g.0.05%, methacrylic acid L-30D in the range of 15 to 35% by weight, more preferably 23 to 28% by weight, e.g.25%, cetyl alcohol in the range of 0.1 to 1.5% by weight, more preferably 0.5 to 1% by weight, e.g.0.76% and purified talc in the range of 0.002 to 0.02% by weight, more preferably 0.003 to 0.01% by weight, e.g.0.007%, based on the total weight of pellets that are filled in hard gelatin capsules.
The preferable omeprazole enteric coated pellets: which comprises omeprazole enteric-coated pellets are in the range of 5 to 15% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
A stable pharmaceutical formulations for antiulcerative substituted benzimidazoles, which comprises esomeprazole or a salt thereof; stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate; mannitol, starch,
crospovidone, polyvinylpyrrolidone s-630; or polyvinylpyrrolidone k-30, hydroxypropylcellulose or hydroxypropylcellulose (low-substituted); acryl EZE, croscarmellose sodium, light calcium carbonate, sodium stearyl fumarate, hydroxypropylmethylcellulose-15cps, sodium lauryl sulfate, propylene glycol, hydroxypropylmethylcellulose E5 and opadry enteric pink.
The present invention provides a formulation suitable for esomeprazole enteric coated tablets or pellets comprising esomeprazole or a salt thereof in the range of 7 to 40% by weight equivalent to esomeprazole, croscarmellose sodium in the range of 1.5 to 4.5% by weight, crospovidone in the range of 1.5 to 4.5% by weight, sodium lauryl sulfate in the range of 0.1 to 1.0% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 20 to 63% by weight, light calcium carbonate in the range of 4 to 11 % by weight; polyvinylpyrrolidone k-30 or polyvinylpyrrolidone s-630 in the range of 0.5 to 4% by weight; hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose in the range of 7 to 24% by weight; mannitol in the range of 9 to 67% by weight, hydroxypropylmethylcellulose E5 in the range of 4.5 to 11.5% by weight, starch in the range of 0.5 to 2.5% by weight, propylene glycol in the range of 0.25 to 1.5% by weight, sodium stearyl fumarate in the range of 0.5 to 2.5% by weight, hydroxypropylmethylcellulose-15cps in the range of 2.5 to 15% by weight, acryl EZE in the range of 7 to 25% by weight and opadry enteric pink in the range of 9 to 21% by weight.based on the total weight of pharmaceutical dosage form. Optionally additional excipients may be used. Particularly preferred additives heavy magnesium oxide, heavy calcium carbonate, heavy magnesium carbonate, heavy sodium carbonate and mannitol.
The preferable esomeprazole enteric coated tablets comprising esomeprazole or a salt thereof in the range of 15 to 31% by weight equivalent to esomeprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 30 to 49% by weight; hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose in the range of 14 to 17% by weight; mannitol in the range of 17 to 21% by weight, polyvinylpyrrolidone s-630 in the range of 1.5 to 2.5% by weight, starch in the range of 1 to 1.5% by weight, sodium stearyl
fumarate in the range of 1 to 2% by weight, hydroxypropylmethylcellulose- 15cps in the range of 4.5 to 5.5% by weight and acryl EZE in the range of 13 to 16% by weight, based on the total weight of enteric-coated tablets. More preferable enteric-coated tablet formulations are: i) Esomeprazole enteric coated tablets (20mg): which comprises esomeprazole or a salt thereof is 17.2% by weight equivalent to esomeprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 44.4% by weight; mannitol is 18.5% by weight, polyvinylpyrrolidone s-630 is 1.92% by weight, sodium stearyl fumarate is 1.54% by weight, starch is 1.15% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose is 15.4% by weight; hydroxypropylmethylcellulose-15cps is 5% by weight and acryl EZE is 14% by weight, based on the total weight of enteric coated tablets, ii) Esomeprazole enteric coated tablets (40 mg): which comprises esomeprazole or a salt thereof is 27.9% by weight equivalent to esomeprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 33.4% by weight; mannitol is 18.8% by weight, polyvinylpyrrolidone s-630 is 2.19% by weight, starch is 1.25% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose is 15% by weight; sodium stearyl fumarate is 1.56% by weight, hydroxypropylmethylcellulose-15cps is 5% by weight and acryl EZE is 14% by weight, based on the total weight of enteric coated tablets.
The preferable esomeprazole enteric coated pellets: which comprises esomeprazole or a salt thereof in the range of 12 to 15% by weight equivalent to esomeprazole, light calcium carbonate in the range of 6.5 to 8.5% by weight, croscarmellose sodium in the range of 2.5 to 3% by weight, crospovidone in the range of 2.5 to 3% by weight, sodium lauryl sulfate in the range of 0.3 to 0.8% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 33 to 41% by weight; mannitol in the range of 20 to 52% by weight, polyvinylpyrrolidone s-630 or polyvinylpyrrolidone k-30 in the range of 1 to 2.5% by weight; starch in the range of 0.5 to 1.5% by weight, hydroxypropylmethylcellulose E5 in the range of 7 to 9% by weight, hydroxypropylmethylcellulose-15cps in the range of 9 to 11% by weight,
propylene glycol in the range of 0.5 to 1% by weight, acryl EZE in the range of 14 to 17% by weight and opadry enteric pink in the range of 14 to 17% by weight, based on the total weight of pellets that are filled in hard gelatin capsules. The preferable esomeprazole enteric coated pellets: which comprises esomeprazole enteric-coated pellets are in the range of 10 to 20% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
A stable pharmaceutical formulations for antiulcerative substituted benzimidazoles, which comprises lansoprazole or (S)-Iansoprazole; calcium carboxymethylcellulose, light magnesium carbonate, lactose, sucrose, methacrylic acid L-30D, mannitol, polyvinylpyrrolidone k-30 hydroxypropylmethylcellulose E5, starch, propylene glycol, sodium hydroxide tween 80, diethyl phthalate, titanium dioxide and cetyl alcohol.
The preferable lansoprazole enteric coated pellets: which comprises lansoprazole in the range of 5 to 12% by weight, more preferably 7 to 10% by weight, e.g. 8.47%, light magnesium carbonate in the range of 3 to 10% by weight, more preferably 5.5 to 7.5% by weight, e.g. 6.58%, lactose in the range of 3 to 10% by weight, more preferably 5.5 to 7.5 % by weight, e.g. 6.58%, sucrose in the range of 10 to 24% by weight, more preferably 15 to 19% by weight, e.g. 16.8%, calcium carboxymethylcellulose in the range of 2 to 7% by weight, more preferably 4 to 6 % by weight, e.g. 4.98%, mannitol in the range of 5 to 14% by weight, more preferably 8 to 11% by weight, e.g. 9.97%, tween 80. in the range of 0.1 to 0.5% by weight, more preferably 0.1 to 0.4% by weight, e.g. 0.35%, polyvinylpyrrolidone k-30 in the range of 0.1 to 0.5% by weight, more preferably 0.1 to 0.3% by weight, e.g. 0.2%, starch in the range of 4 to 11%by weight, more preferably 6 to 8% by weight, e.g. 7.21%, methacrylic acid L-30D in the range of 14.5 to 35% by weight, more preferably 22 to 28% by weight, e.g. 24.9%, hydroxypropylmethylcellulose E5 in the range of 5 to 13% by weight, more preferably 7.5 to 10% by weight, e.g. 8.72%, propylene glycol in the range of 0.2 to 1.5% by weight, more preferably 0.5 to 1% by weight.e.g. 0.81%, sodium hydroxide in the range of 0.05 to 0.25% by weight, more preferably 0.1 to 0.2% by weight,e.g.0.14%, diethyl phthalate in the range of 1 to 3.5% by weight, more preferably 2 to 3% by weight, e.g. 2.49%, titanium dioxide in the range of 0.5 to 2% by weight, more preferably
0.5 to 1.5% by weight, e.g. 0.4% and cetyl alcohol in the range of 0.1 to 1.5% by weight, more preferably 0.5 to 1 % by weight, e.g. 0.75%, based on the total weight of pellets that are filled in hard gelatin capsules.
The preferable lansoprazole enteric coated pellets: which comprises lansoprazole enteric-coated pellets are in the range of 5 to 15% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
The preferable (S)-Iansoprazole enteric coated pellets: which comprises (S)-Iansoprazole in the range of 5 to 12% by weight, more preferably 7 to 10% by weight, e.g. 8.47%, light magnesium carbonate in the range of 3 to 10% by weight, more preferably 5.5. to 7.5% by weight, e.g. 6.58%, lactose in the range of 3 to 10% by weight, more preferably 5.5 to 7.5 % by weight, e.g. 6.58%, sucrose in the range of 10 to 24% by weight, more preferably 15 to 19% by weight, e.g. 16.8%, calcium carboxymethylcellulose in the range of 2 to 7% by weight, more preferably 4 to 6 % by weight,e.g. 4.98%, mannitol in the range of 5 to 14% by weight, more preferably 8 to 11% by weight,e.g. 9.97%, tween 80 in the range of 0.1 to 0.5% by weight, more preferably 0.1 to 0.4% by weight,e.g.0.35%, polyvinylpyrrolidone k-30 in the range of 0.1 to 0.5% by weight, more preferably 0.1 to 0.3% by weight.e.g. 0.2%, starch in the range of 4 to 11%by weight, more preferably 6 to 8% by weight, e.g. 7.21%, methacrylic acid L-30D in the range of 14.5 to 35% by weight, more preferably 22 to 28% by weight, e.g. 24.9%, hydroxypropylmethylcellulose E5 in the range of 5 to 13% by weight, more preferably 7.5 to 10% by weight, e.g. 8.72%, propylene glycol in the range of 0.2 to 1.5% by weight, more preferably 0.5 to 1% by weight, e.g. 0.81%, sodium hydroxide in the range of 0.05 to 0.25% by weight, more preferably 0.1 to 0.2% by weight, e.g. 0.14%, diethyl phthalate in the range of 1 to 3.5% by weight, more preferably 2 to 3% by weight, e.g. 2.49%, titanium dioxide in the range of 0.5 to 2% by weight, more preferably 0.5 to 1.5% by weight, e.g. 0.4% and cetyl alcohol in the range of 0.1 to 1.5% by weight, more preferably 0.5 to 1 % by weight, e.g. 0.75%, based on the total weight of pellets that are filled in hard gelatin capsules.
The preferable (S)-lansoprazole enteric coated pellets: which comprises (S)-lansoprazole enteric-coated pellets are in the range of 5 to 15% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
The pharmaceutical composition may be for example, in the form of a tablet, a caplet, pellets, a capsule, granules, a pill, powder or a sachet.
Preferably the pharmaceutical composition is in the form of pellets, tablets and capsules. The capsule may contain powder, compressed powder, pellets or granules.
The invention is explained in detail in the examples given below which are provided by way of illustration only and therefore should not be construed to limit. the scope of the invention.
EXAMPLES In the following embodiments of the invention, the below listed quantities of drug substance and additional components are combined using standard pharmaceutical manufacturing techniques. The resulting formulations are used to fill gelatin capsule shells or compressed into tablets. Enteric-coated tablet formulation: Method of manufacture: The antiulcerative substituted benzimidazole, stabilizer and mannitol are granulated using binder solution of polyvinylpyrrolidone s-630 and starch in planetary mixer, rapid mixer granulator; or other suitable granulator. This wet mass may be then dried in a fluid bed dryer, tray dryer; or other suitable dryer. The dried granulation may be then milled to acheive the desired particle size distribution and then blended with the other ingredients. This blend is compressed into tablets. These compressed tablets are seal coated using an aqueous solution of hydroxypropylmethylcellulose-15cps and seal coated tablets are enteric coated using an aqueous dispersion of acryl EZE by using autocota, neocota; or other suitable coating pan.
Example 1
The components and their amounts were as follows: Rabeprazole sodium enteric coated (10mg) tablets: Ingredients Quantity (mg) %(W/W) Active coating
Rabeprazole sodium 10 7.69
Heavy magnesium oxide 70 53.8'
Mannitol 24 18.5
Polyvinylpyrrolidone s-630 2.5 1.92
Starch 1.5 1.15
Hydroxypropylcellulose (klucel LF) 20 15.4
Sodium stearyl fumarate 2 1.54
Tablet weight 130
Seal Coating
Hydroxypropylmethylcellulose-Iδcps 6.5
Enteric Coating
Acryl EZE 19.1 " 14
Example 2
The components and their amounts were as follows: Rabeprazole sodium enteric coated (20mg) tablets:
Ingredients Quantity (mg) %(W/W)
Active coating
Rabeprazole sodium 20 12.5
Heavy calcium carbonate 78 48.8
Mannitol 30 18.8
Polyvinylpyrrolidone s-630 3.5 2.19
Starch 2 1.25
L-hydroxypropylcellulose (LH-11) 24 15
Sodium stearyl fumarate 2.5 1.56
Tablet weight 160
Seal Coating
Hydroxypropylmethylcellulose-15cps 8
Enteric Coating
Acryl EZE 23.52 14
Example 3
The components and their amounts were as follows: Pantoprazole enteric coated (20mg) tablets:
Ingredients Quantity (mg) %(W/W)
Active coating
Pantoprazole sodium sesquihydrate
Eq to pantoprazole 22.6 17.4
Heavy magnesium carbonate 57.4 44.2
Mannitol 24 18.5
Polyvinylpyrrolidone s-630 2.5 1.92
Starch 1.5 1.15
Hydroxypropylcellulose (klucel LF) 20 15.4
Sodium stearyl fumarate 2 1.54
Tablet weight 130 -
Seal Coating
Hydroxypropylmethylcellulose-Iδcps 6.5 5
Enteric Coating
Acryl EZE 19.11 14
Example 4
The components and their amounts were as follows: Pantoprazole enteric coated (40mg) tablets:
Ingredients Quantity (mg) %(W/W)
Active coating
Pantoprazole sodium sesquihydrate
Eq to pantoprazole 45.2 28.3 H Heeaavvyy ssooddiiuumm ccaarrbboonnaattee 5 522..88 33
Mannitol 30 18.8
Polyvinylpyrrolidone s-630 3.5 2.19
Starch 2 1.25
L-hydroxypropylcellulose (LH-11) 24 15 S Sooddiiuumm sstteeaarryyll ffuummaarraattee 2 2..55 1.56
Tablet weight 160
Seal Coating
Hydroxypropylmethylcellulose-15cps 8
Enteric Coating A Accrryyll EEZZEE 2233..5522 14
Example 5
The components and their amounts were as follows: Esomeprazole enteric coated (20mg) tablets:
Ingredients Quantity (mg) %(W/W)
Active coating
Esomeprazole magnesium trihydrate
Eq to Esomeprazole 22.3 17.2
Heavy magnesium oxide 57.7 44.4
Mannitol 24 18.5
Polyvinylpyrrolidone s-630 2.5 1.92
Starch 1.5 1.15
Hydroxypropylcellulose (klucel LF) 20 15.4
Sodium stearyl fumarate 2 1.54
Tablet weight 130
Seal Coating
Hydroxypropylmethylcellulose-15cps 6.5
Enteric Coating
Acryl EZE 19.11 14
Example 6
The components and their amounts were as follows: Esomeprazole enteric coated (40mg) tablets:
Ingredients Quantity (mg) %(W/W)
Active coating
Esomeprazole magnesium trihydrate
Eq to esomeprazole 44.6 27.9
Heavy magnesium carbonate 53.4 33.4
Mannitol 30 18.8
Polyvinylpyrrolidone S-630 3.5 2.19
Starch 2 1.25
L-hydroxypropyl cellulose (LH-11) 24 15
Sodium stearyl fumarate 2.5 1.56
Tablet weight 160
Seal Coating
Hydroxypropylmethylcellulose-15cps 8
Enteric Coating
Acryl EZE 23.52 14
Enteric-coated pellets formulation: Method of manufacture: A. Active coating
The antiulcerative substituted benzimidazole; stabilizer and mannitol are granulated using binder having polyvinylpyrrolidone s-630 and starch in planetary mixer, rapid mixer granulator; or other suitable granulator. This wet mass then may be thread like pieces in extruder. Thread like pieces then may be spherical wet pellets in spherodizer. This spherical wet pellets then may be dried in a fluid bed dryer, tray dryer; or other suitable dryer. B. Intermediate coating
The spherical wet pellets are coated using an aqueous solution of hydroxypropylmethylcellulose in fluid bed coater or other suitable coater. C. Enteric coating
The intermediate coated pellets are coated using an aqueous dispersion of acryl EZE in fluid bed coater or other suitable coater.
The enteric-coated pellets are filled into hard gelatin capsules.
Example 7
The components and their amounts were as follows: Rabeprazole sodium enteric-coated pellets:
Ingredients Quantity (mg) %(W/W)
Active coating
Rabeprazole sodium 10 8
Heavy sodium carbonate 70 52.2 M Maannnniittooll 2 244 17.9
Polyvinylpyrrolidone s-630 2.5 1.86
Starch 1.5 1.12
Intermediate coating .
Hydroxypropylmethylcellulose 15cps 7.6
Enteric coating
Acryl EZE 13.9 12
Example 8 The components and their amounts were as follows:
Pantoprazole sodium enteric-coated pellets:
Ingredients Quantity (mg) %(W/W)
Active coating
Pantoprazole sodium sesquihydrate
Eq to pantoprazole 22.6 13
Heavy magnesium oxide 60 37.2
Mannitol 36 22.3
Polyvinylpyrrolidone S-630 2.5 1.55
Starch 1.5 0.93
Intermediate coating
Hydroxypropylmethylcellulose 15cps 12.3 10
Enteric coating
Acryl EZE 20.3 15
Example 9
The components and their amounts were as follows:
Esomeprazole enteric-coated pellets:
Ingredients Quantity (mg) %(WΛ
Active coating Esomeprazole magnesium trihydrate
Eq to esomeprazole 22.3 • 13
Heavy calcium carbonate 60 37.2
Mannitol 36 22.3
Polyvinylpyrrolidone s-630 2.5 1.55 Starch 1.5 0.93
Intermediate coating
Hydroxypropylmethyl cellulose 15cps 12.26 10
Enteric coating
Acryl EZE 20.25 15 Enteric-coated pellets formulation:
Manufacture of rabeprazole sodium or (S)- rabeprazole sodium:
A. Active coating
The rabeprazole sodium or (S)- rabeprazole sodium, stabilizer and hydroxypropyl cellulose LF are dissolved in non-aqueous solution. The drug
solution is loaded on mannitol to get the drug pellets. This drug pellets may be then dried in a fluid bed dryer, tray dryer; or other suitable dryer. B.lntermedϊate coating
The drug pellets are coated using non-aqueous solution of opadry oraganic in fluid bed coater; or other suitable coater. C. Enteric coating
The intermediate coated pellets are coated using non-aqueous solution of opadry enteric in fluid bed coater; or other suitable coater. The enteric-coated pellets are filled into hard gelatin capsules.
Example 10
The components and their amounts were as follows: Rabeprazole sodium enteric-coated pellets:
Ingredients Quantity (mg) %(W/W) Active coating
Rabeprazole sodium 10 8
Light magnesium oxide 2 1.49
Hydroxypropylcellulose (klucel LF) 2 1.49
Ethanol Mannitol 94 70.02
Intermediate coating
Opadry organic white 7.6 7
Enteric coating
Opadry enteric pink 13.9 12 Enteric-coated pellets formulation:
Manufacture of pantoprazole, (S)- pantoprazole and esomeprazole or a salt thereof:
A. Active coating
The pantoprazole, (S)-pantoprazoIe and esomeprazole or a salt thereof, stabilizer, crospovidone, croscarmellose sodium, sodium lauryl sulfate and mannitol are blended. Mannitol is wetted using binder having polyvinylpyrrolidone k-30. The above blend is loaded on wet mannitol. These drug pellets may be then dried in a fluid bed dryer, tray dryer; or other suitable dryer.
B.lntermediate coating
The drug pellets are coated using non-aqueous solution of hydroxypropylmethyl cellulose E5 and propylene glycol in fluid bed coater; or other suitable coater.
C. Enteric coating
The intermediate coated pellets are coated using non-aqueous solution of opadry enteric in fluid bed coater; or other suitable coater.
The enteric-coated pellets are filled into hard gelatin capsules.
Example 11
The components and their amounts were as follows:
Pantoprazole enteric-coated pellets:
Ingredients Quantity (mg) %(W/W)
Active coating
Pantoprazole sodium sesquihydrate
Eq to pantoprazole 22.6 13
Light calcium carbonate 12 7.51
Crospovidone 5 3.13
Croscarmellose sodium 5 3.13
Sodium lauryl sulfate 0.8 0.5
Mannitol 25 15.6
Polyvinylpyrrolidone k-30 3.3 2.06 lsopropyl alcohol q.s
Mannitol 30 18.8
Mannitol 20 12.5
Intermediate coating
Hydroxypropyimethylcellulose E5 9.92 8
Propylene glycol 0.992 0.8
Enteric coating
Opadry enteric pink 20.25 15
Example 12
The components and their amounts were as follows: Esomeprazole enteric-coated pellets:
Ingredients Quantity (mg) %(W/W)
Active coating
Esomeprazole magnesium trihydrate
Eq to esomeprazole 22.3 13 Light calcium carbonate 12 7.46
Crospovidone 5 3.11
Croscarmellose sodium 5 3.11
Sodium lauryl sulfate 0.8 0.5
Mannitol 25 15.5 Polyvinylpyrrolidone k-30 3.5 2.18 lsopropyl alcohol q.s -
Mannitol 30.4 18.9
Mannitol 20 12.4
Intermediate coating Hydroxypropylmethylcellulose E5 9.92 8
Propylene glycol 0.99 0.8
Enteric coating
Opadry enteric pink 20.3 15
Enteric-coated pellets formulation: Manufacture of omeprazole; or a salt thereof:
A. Active coating
The omeprazole or a salt thereof, calcium carbonate, mannitol, sodium lauryl sulfate, lactose, disodium hydrogen phosphate and sucrose are blended.
Sucrose is wetted using binder having sucrose syrup. The above blend is loaded on wet sucrose. These drug pellets may be then dried in a fluid bed dryer; tray dryer; or other suitable dryer.
B.lntermediate coating
The drug pellets are coated using aqueous solution of hydroxypropylmethyl cellulose E5, polyvinylpyrrolidone k-30 and propylene glycol in fluid bed coater; or other suitable coater.
C. Enteric coating
The intermediate coated pellets are coated using aqueous solution of methacrylic acid L-30D, sodium hydroxide, tween 80, diethyl phthalate, titanium
dioxide, cetyl alcohol and purified talc in fluid bed coater; or other suitable coater.
The enteric-coated pellets are filled into hard gelatin capsules.
Example 13
The components and their amounts were as follows:
Omeprazole enteric-coated pellets:
Ingredients Quantity (mg) %(W/V
Active coating Omeprazole 10 8.47
Mannitol 20.06 17
Calcium carbonate 4 3.39
Sodium lauryl sulfate 0.4 0.34
Lactose 4 3.39 Sucrose 32.5 27.5
Disodium hydrogen phosphate 1.5 1.27
Intermediate coating
Hydroxypropylmethylcellulose E5 10.34 8.76
Polyvinylpyrrolidone k-30 0.3 0.25 Propylene glycol 1 0.85
Enteric coating
Methacrylic acid L-30D 29.5 25
Sodium hydroxide 0.18 0.15
Tween 80 0.3 0.25 Diethyl phthalate 2.95 2.5
Titanium dioxide 0.06 0.05
Cetyl alcohol 0.9 0.76
Purified talc 0.008 0.01
Enteric-coated pellets formulation: Manufacture of lansoprazole or (S)-lansoprazole:
A. Active coating
The lansoprazole or (S)-lansoprazole, magnesium carbonate, mannitol, calcium carboxymethylcellulose, lactose, starch and sucrose are blended. Sucrose is wetted using binder. The above blend is loaded on wet sucrose.
These drug pellets may be then dried in a fluid bed dryer, tray dryer; or other suitable dryer. B.lntermediate coating
The drug pellets are coated using aqueous solution of hydroxypropyl methyl cellulose E5, polyvinylpyrrolidone k-30, acetone and propylene glycol in fluid bed coater; or other suitable coater. C. Enteric coating
The intermediate coated pellets are coated using aqueous solution of methacrylic acid L-30D, sodium hydroxide, tween 80, diethyl phthalate, titanium dioxide and cetyl alcohol in fluid bed coater; or other suitable coater. The enteric-coated pellets are filled into hard gelatin capsules.
Example 14
The components and their amounts were as follows:
Lansoprazole enteric-coated pellets:
Ingredients Quantity (mg) %(W/W)
Active coating
Lansoprazole 30 8.47
Mannitol 35.29 9.97
MMaaggnneessiiuumm ccaarrbboonnaattee 2233..2299 6.58
Calcium carboxymethylcellulose 17.64 4.98
Lactose 23.29 6.58
Starch 25.54 7.21
Sucrose 58.56 16.8
Intermediate coating
Hydroxypropylmethylcellulose E5 30.88 8.72
Polyvinylpyrrolidone k-30 0.70 0.2
Propylene glycol 2.85 0.81
Enteric coating
MMeetthhaaccrryylliicc aacciidd LL--3300DD 8888..2233 24.9
Cetyl alcohol 2.64 0.75
Titanium dioxide 3.53 1
Tween 80 1.23 0.35
Sodium hydroxide 0.5 0.14
Diethyl phthalate 8.82 2.49
A single dosage unit capsule formulations:
The antiulcerative substituted benzimidazoles are rabeprazole, pantoprazole, omeprazole, lansoprazole, tenatoprazole, esomeprazole, (S)- pantoprazole, (S)-rabeprazole and (S)-lansoprazole or a salt thereof as enteric coated pellets or tablets and optionally in combination with other active pharmaceutical ingredients are domperidone, itopride hydrochloride, mosapride citrate and ondansetron as sutained release pellets or pellets are filled in required size hard gelatin capsules in various combination of single dosage units.
Example 15 Rabeprazole sodium (10mg)(EC) and domperidone (30mg)(SR) capsules
Ingredients Quantity (mg) %(W/V
Rabeprazole sodium
(As enteric coated pellets) (8%) 130 46.4
Domperidone
(As sustained release pellets) (24%) 125 44.6
Dummy pellets 25 8.93
Capsule target weight 280 -
Empty hard gelatin capsules 1 No's -
Example 16 (S)-rabeprazole sodium (20mg)(EC) and domperidone (30mg)(SR) capsules
Ingredients Quantity (mg) %(Wi
(S)-rabeprazole sodium
(As enteric coated pellets) (8%) 260 63
Domperidone
(As sustained release pellets) (24%) 125 30
Dummy pellets 25 6.1
Capsule target weight 410 -
Empty hard gelatin capsules 1 No's _
Example 17 (S)-rabeprazole sodium (10mg)(EC) and domperidone (10mg) capsules:
Ingredients Quantity (mg) %(WΛ
(S)-rabeprazole sodium
(As enteric coated pellets) (8%) 130 46.4
Domperidone
(As pellets) (12%) 84 30
Dummy pellets 66 23.6
Capsule target weight 280 -
Empty hard gelatin capsules 1 No's -
Example 18 Rabeprazole sodium (20mg)(EC) and domperidone (10mg) capsules:
Ingredients Quantity (mg) %(W/
Rabeprazole sodium
(As enteric coated pellets) (8%) 260 63.4
Domperidone
(As pellets) (12%) 84 20.5
Dummy pellets 66 16.1
Capsule target weight 410 -
Empty hard gelatin capsules 1No's -
Example 19
(S)-rabeprazole sodium (10mg)(EC) and itopride hydrochloride (150mg)(SR) capsules:
Ingredients Quantity (mg) %(W/V
(S)-rabeprazole sodium
(As enteric coated pellets) (8%) 130 33.33
Itopride hydrochloride
(As sustained release pellets) (64%) 235 60.26
Dummy pellets 25 6.4
Capsule target weight 390 -
Empty hard gelatin capsules 1 No's -
Example 20
Rabeprazole sodium (20mg)(EC) and itopride hydrochloride (150mg)(SR) capsules:
Ingredients Quantity (mg) %(W/ Rabeprazole sodium (As enteric coated pellets) (8%) 260 50.98
Itopride hydrochloride
(As sustained release pellets) (64%) 235 46.08
Dummy pellets 15 2.9 Capsule target weight 510 -
Empty hard gelatin capsules 1 No1S -
Example 21
Rabeprazole sodium (10mg)(EC) and itopride hydrochloride (50mg) capsules: Ingredients Quantity (mg) %(W/W)
Rabeprazole sodium
(As enteric coated pellets) (8%) 130 45.3
Itopride hydrochloride
(As pellets) (32%) 157 54.7 Capsule target weight 287
Empty hard gelatin capsules 1 No's
Example 22
(S)-rabeprazole sodium (20mg)(EC) and itopride hydrochloride (50mg) capsules:
Ingredients Quantity (mg) %(W/W)
(S)-rabeprazole sodium
(As enteric coated pellets) (8%) 260 62.35
Itopride hydrochloride (As pellets) (32%) 157 37.65
Capsule target weight 417
Empty hard gelatin capsules 1 No's
Example 23 Rabeprazole sodium (10mg)(EC) and mosapride citrate (15mg)(SR) capsules:
Ingredients Quantity ( mg) %(WΛ
Rabeprazole sodium
(As enteric coated pellets) (8%) 130 46.4
Mosapride citrate dihydrate
Eq .to mosapride citrate
(As sustain release pellets) (12%) 125 44.6
Dummy pellets 25 8.9
Capsule target weight 280 -
Empty hard gelatin capsules 1 No's -
Example 24
(S)-rabeprazole sodium (20mg)(EC) and mosapride citrate (15mg)(SR) capsules:
Ingredients Quantity (mg) %(W
(S)-rabeprazole sodium
(As enteric coated pellets) (8%) 260 63
Mosapride citrate dihydrate
Eq.to mosapride citrate
(As sustain release pellets) (12%) 125 30
Dummy pellets 25 6.1
Capsule target weight 410 -
Empty hard gelatin capsules 1No's -
Example 25 (S)-rabeprazole sodium (10mg)(EC) and mosapride citrate (5mg) capsules:
Ingredients Quantity (mg) %(W/
(S)-rabeprazole sodium
(As enteric coated pellets) (8%) 130 46.^
Mosapride citrate dihydrate
Eq.to mosapride citrate
(As pellets) (6%) 84 30
Dummy pellets 66 23.6
Capsule target weight 280
Empty hard gelatin capsules 1No's
Example 26 Rabeprazole sodium (20mg)(EC) and mosapride citrate (5mg) capsules:
Ingredients Quantity (mg) %(w/w;
Rabeprazole sodium
(As enteric coated pellets) (8%) 260 67.5
Mosapride citrate dihydrate
Eq. to mosapride citrate
(As pellets) (6%) 84 21.82
Dummy pellets 41 10.65
Capsule target weight 385
Empty hard gelatin capsules 1No's -
Example 27 (S)-rabeprazole sodium (10mg)(EC) and ondansetron (12mg)(SR) capsules:
Ingredients Quantity (mg) %(WΛ
(S)-rabeprazole sodium
(As enteric coated pellets) (8%) 130 46.4
Ondansetron
(As sustained release pellets) (12%) 100 35.7
Dummy pellets 50 17.6
Capsule target weight 280 -
Empty hard gelatin capsules 1No's -
Example 28
The components and their amounts were as follows: Rabeprazole sodium (20mg)(EC) and ondansetron (12mg)(SR) capsules: Ingredients Quantity (mg) %(W/W)
Rabeprazole sodium
(As enteric coated pellets) (8%) 260 63.4
Ondansetron (As sustained release pellets) (12%) 100 24.4
Dummy pellets 50 12.2
Capsule target weight 410
Empty hard gelatin capsules 1 No's
Example 29 Rabeprazole sodium (10mg)(EC) and ondansetron (4mg) capsules:
Ingredients Quantity (mg) %(W/V
Rabeprazole sodium
(As enteric coated pellets) (8%) 130 46.4
Ondansetron
(As pellets) (4%) 100 35.7
Dummy pellets 50 17.9
Capsule target weight 350 -
Empty hard gelatin capsules 1 No's -
Example 30
(S)-rabeprazole sodium (20mg)(EC) and ondansetron (4mg) capsules:
Ingredients Quantity (mg) %(W/V
(S)-rabeprazole sodium
(As enteric coated pellets) (8%) 260 63
Ondansetron
(As pellets) (4%) 100 24
Dummy pellets 50 12
Capsule target weight 410 -
Empty hard gelatin capsules 1 No1S -
Example 31
Pantoprazole (20mg)(EC) and domperidone (30mg)(SR) capsules: Ingredients Quantity (mg) %(W/W) Pantoprazole sodium sesquihydrate Eq. to pantoprazole
(As enteric coated pellets) (13%) 155 44.3
Domperidone (As sustained release pellets) (24%) 125 ' 35.7
Dummy pellets 70 20
Capsule target weight 350
Empty hard gelatin capsules 1 No's
Example 32 (S)-pantoprazole (40mg)(EC) and domperidone (30mg)(SR) capsules:
Ingredients Quantity (mg) %(W
(S)-pantoprazole sodium sesquihydrate
Eq. to (S)-pantoprazole
(As enteric coated pellets) (13%) 310 60.8
Domperidone
(As sustained release pellets) (24%) 125 24.5
Dummy pellets 75 14.7
Capsule target weight 510 -
Empty hard gelatin capsules 1No's -
Example 33
(S)-pantoprazole (20mg)(EC) and domperidone (10mg) capsules: Ingredients Quantity (mg) %(W/W) (S)-pantoprazole sodium sesquihydrate
Eq. to (S)-pantoprazole
(As enteric coated pellets) (13%) 155 62
Domperidone
(As pellets) (12%) 84 33.6 Dummy pellets 11 4.4
Capsule target weight 250 -
Empty hard gelatin capsules 1No's _
Example 34 Pantoprazole (40mg)(EC) and domperidone (10mg) capsules:
Ingredients Quantity (mg) %(W/W)
Pantoprazole sodium sesquihydrate
Eq. to pantoprazole
(As enteric coated pellets) (13%) 310 77.5
Domperidone
(As pellets) (12%) , 84 21
Dummy pellets 6 1.5
Capsule target weight 400 -
Empty hard gelatin capsules 1 No's -
Example 35
(S)-pantoprazole (20mg)(EC) and itopride hydrochloride (150mg)(SR) capsules:
Ingredients Quantity (mg) %(W/W)
(S)-pantoprazole sodium sesquihydrate
Eq. to (S)-pantoprazoIe
(As enteric coated pellets) (13%) 155 38.8 ltopride hydrochloride
(As sustained release pellets) (64%) 235 58.8
Dummy pellets 10 2.5
Capsule target weight 400 -
Empty hard gelatin capsules 1No's -
Example 36 Pantoprazole (40mg)(EC) and itopride hydrochloride (150mg)(SR) capsules:
Ingredients Quantity (mg) %(VM
Pantoprazole sodium sesquihydrate
Eq. to pantoprazole
(As enteric coated pellets) (13%) 310 55.9
Itopride hydrochloride
(As sustained release pellets) (64%) 235 42.3
Dummy pellets 10 1.8
Capsule target weight 555 -
Empty hard gelatin capsules 1 No's -
Example 37
Pantoprazole (20mg)(EC) and itopride hydrochloride (50mg) capsules: Ingredients Quantity (mg) %(W/W)
Pantoprazole sodium sesquihydrate
Eq. to pantoprazole
(As'enteric coated pellets) (13%) 155 46.7 ltopride hydrochloride
(As pellets) (32%) 157 47.3
Dummy pellets 20 6
Capsule target weight 332 -
Empty hard gelatin capsules 1No's _
Example 38
(S)-pantoprazole (40mg)(EC) and itopride hydrochloride (50mg) capsules:
Ingredients Quantity (mg) %(V\
(S)-pantoprazole sodium sesquihydrate
Eq. to (S)-pantoprazole
(As enteric coated pellets) (13%) 310 62.4
Itopride hydrochloride
(As pellets) (32%) 157 31.6
Dummy pellets 30 6
Capsule target weight 497 -
Empty hard gelatin capsules 1No's _
Example 39 Pantoprazole (20mg)(EC) and mosapride citrate (15mg)(SR) capsules:
Ingredients Quantity (mg) %(wy
Pantoprazole sodium sesquihydrate
Eq. to paηtoprazole
(As enteric coated pellets) (13%) 155 50
Mosapride citrate dihydrate
Eq. to mosapride citrate
(As sustained release pellets) (12%) . 125 40.3
Dummy pellets 30 9.68
Capsule target weight 310 -
Empty hard gelatin capsules 1No's -
Example 40
(S)-pantoprazole (40mg)(EC) and mosapride citrate (15mg)(SR) capsules:
Ingredients Quantity (mg) %(W/W)
(S)-pantoprazole sodium sesquihydrate Eq. to (S)-pantoprazole
(As enteric coated pellets) (13%) 310 68.9
Mosapride citrate dihydrate
Eq .to mosapride citrate
(As sustained release pellets) (12%) 125 27.8 Dummy pellets 15 3.33
Capsule target weight 450 -
Empty hard gelatin capsules 1 No's _
Example 41 (S)-pantoprazole (20mg)(EC) and mosapride citrate (5mg) capsules:
Ingredients Quantity (mg) %(V\
(S)-pantoprazole sodium sesquihydrate
Eq. to (S)-pantoprazole
(As enteric coated pellets) (13%) 155 62
Mosapride citrate dihydrate
Eq .to mosapride citrate
(As pellets) (6%) 84 33.6
Dummy pellets 11 4.4
Capsule target weight 250 -
Empty hard gelatin capsules 1 No's -
Example 42
Pantoprazole (40mg)(EC) and mosapride citrate (5mg) capsules: Ingredients Quantity (mg) %(W/W) Pantoprazole sodium sesquihydrate Eq. to pantoprazole
(As enteric coated pellets) (13%) 310 77.5
Mosapride citrate dihydrate Eq.to mosapride citrate
(As pellets) (6%) 84 21
Dummy pellets 6 1.5
Capsule target weight 400 -
Empty hard gelatin capsules 1 No's -
Example 43
(S)-pantoprazole (20mg)(EC) and ondansetron (12mg)(SR) capsules:
Ingredients Quantity (mg) %(W/W)
(S)-pantoprazole sodium sesquihydrate Eq. to (S)-pantoprazole
(As enteric coated pellets) (13%) 155 60.8
Ondansetron
(As sustained release pellets) (12%) 100 39.2
Capsule target weight 255 Empty hard gelatin capsules 1 No's
Example 44 Pantoprazole (40mg)(EC) and ondansetron (12mg)(SR) capsules:
Ingredients Quantity (mg) %(W/W) Pantoprazole sodium sesquihydrate
Eq. to pantoprazole
(As enteric coated pellets) (13%) 310 75.6
Ondansetron
(As sustained release pellets) (12%) 100 24.4 Capsule target weight 410
Empty hard gelatin capsules 1 No's
Example 45
Pantoprazole (20mg)(EC) and ondansetron (4mg) capsules: Ingredients Quantity (mg) %(W/W)
Pantoprazole sodium sesquihydrate
Eq. to pantoprazole
(As enteric coated pellets) (13%) 155 60.8
Ondansetron
(As pellets) (4%) 100 39.2
Capsule target weight 255
Empty hard gelatin capsules 1 No's
Example 46
(S)-pantoprazole (40mg)(EC) and Ondansetron (4mg) capsules:
Ingredients Quantity (mg) %(W/W)
(S)-pantoprazole sodium sesquihydrate
Eq. to (S)-pantoprazoIe (As enteric coated pellets) (13%) 310 75.6
Ondansetron
(As pellets) (4%) 100 24.4
Capsule target weight 410
Empty hard gelatin capsules 1 No's
Example 47
Lansoprazole (15mg)(EC) and domperidone (30mg)(SR) capsules:
Ingredients Quantity (mg) %(WΛ
Lansoprazole (As enteric coated pellets) (8.5%) 177 50.6
Domperidone
(As sustained release pellets) (24%) 125 35.7
Dummy pellets 48 13.7
Capsule target weight 350 - Empty hard gelatin capsules 1No"s -
Example 48 (S)-lansoprazole (30mg)(EC) and domperidone (30mg)(SR) capsules:
Ingredients Quantity (mg)
(S)-lansoprazole
(As enteric coated pellets) (8.5%) 354 70.
Domperidone
(As sustained release pellets) (24%) 125 25
Dummy pellets 21 4.2
Capsule target weight 500 Empty hard gelatin capsules 1 No's
Example 49 (S)-lansoprazole (15mg)(EC) and domperidone (10mg) capsules: ingredients Quantity (mg) %(V!
(S)-lansoprazole
(As enteric coated pellets) (8.5%) 177 59
Domperidone
(As pellets) (12%) 84 . 28
Dummy pellets 39 13
Capsule target weight 300 -
Empty hard gelatin capsules 1 No's _
Example 50 Lansoprazole (30mg)(EC) and domperidone (10mg) capsules:
Ingredients Quantity (mg) %(W/
Lansoprazole
(As enteric coated pellets) (8.5%) 354 78.7
Domperidone
(As pellets) (12%) 84 18.7
Dummy pellets 12 2.7
Capsule target weight 450 -
Empty hard gelatin capsules 1 No's _
Example 51
(S)-lansoprazole (15mg)(EC) and itopride hydrochloride (150mg)(SR) capsules: Ingredients Quantity (mg) %(W/W)
(S)-lansoprazole
(As enteric coated pellets) (8.5%) 177 39.3
Itopride hydrochloride
(As sustained release pellets) (64%) 235 52.2
Dummy pellets 38 8.4
Capsule target weight 450
Empty hard gelatin capsules 1 No's
Example 52
Lansoprazole (30mg)(EC) and itopride hydrochloride (150mg)(SR) capsules: Ingredients Quantity (mg) %(VWW)
Lansoprazole
(As enteric coated pellets) (8.5%) 354 60.1
Itopride hydrochloride
(As sustained release pellets) (64%) 235 39.9 Capsule target weight 589
Empty hard gelatin capsules 1 No's
Example 53 Lansoprazole (15mg)(EC) and itopride hydrochloride (50mg) capsules: Ingredients Quantity (mg) %(W/
Lansoprazole
(As enteric coated pellets) (8.5%) 177 50.6
Itopride hydrochloride
(As pellets) (32%) 157 44.9 Dummy pellets 16 4.6
Capsule target weight 350 -
Empty hard gelatin capsules 1 No's _
Example 54 (S)-Iansoprazole (30mg)(EC) and itopride hydrochloride (50mg) capsules:
Ingredients Quantity (mg) %(W/W)
(S)-lansoprazole
(As enteric coated pellets) (8.5%) 354 69.3
Itopride hydrochloride (As pellets) (32%) 157 30.7
Capsule target weight 511
Empty hard gelatin capsules 1 No's
Example 55 Lansoprazole (15mg)(EC) and mosapride citrate (15mg)(SR) capsules:
Ingredients Quantity (mg) %(W/
Lansoprazole
(As enteric coated pellets) (8.5%) 177 69.3
Mosapride citrate dihydrate
Eq.to mosapride citrate
(As sustained release pellets) (12%) 125 30.7
Dummy pellets 48 13.7
Capsule target weight 350 -
Empty hard gelatin capsules 1 No's -
Example 56
(S)-lansoprazole (30mg)(EC) and mosapride citrate (15mg)(SR) capsules: Ingredients Quantity (mg) %(W/W)
(S)-lansoprazole
(As enteric coated pellets) (8.5%) 354 73.9
Mosapride citrate dihydrate
Eq.to mosapride citrate (As sustained release pellets) (12%) 125 26.1
Capsule target weight 479
Empty hard gelatin capsules 1 No's
Example 57 (S)-lansoprazole (15mg)(EC) and mosapride citrate (5mg) capsules:
Ingredients Quantity (mg) %(M
(S)-lansoprazole
(As enteric coated pellets) (8.5%) 177 59
Mosapride citrate dihydrate
Eq.to mosapride citrate
(As pellets) (6%) 84 28
Dummy pellets 39 13
Capsule target weight 300 -
Empty hard gelatin capsules 1No's -
Example 58
Lansoprazole (30mg)(EC) and Mosapride citrate (5mg) capsules: Ingredients Quantity (mg) %(W/W)
Lansoprazole (As enteric coated pellets) (8.5%) 354 80.8
Mosapride citrate dihydrate
Eq.to mosapride citrate
(As pellets) (6%) 84 19.2
Capsule target weight 438 Empty hard gelatin capsules 1 No's
Example 59 (S)-lansoprazole (15mg)(EC) and ondansetron (12mg)(SR) capsules:
Ingredients Quantity (mg) %(W (S)-lansoprazole
(As enteric coated pellets) (8.5%) 177 54.5
Ondansetron
(As sustained release pellets) (12%) 100 30.8
Dummy pellets 48 14.8 Capsule target weight 325 -
Empty hard gelatin capsules 1No's -
Example 60
Lansoprazole (30mg)(EC) and ondansetron (12mg)(SR) capsules: Ingredients Quantity (mg) %(W/W)
(S)-lansoprazole
(As enteric coated pellets) (8.5%) 354 78
Ondansetron
(As sustained release pellets) (12%) 100 22 Capsule target weight 454
Empty hard gelatin capsules 1 No's
Example 61 Lansoprazole (15mg)(EC) and ondansetron (4mg) capsules:
Ingredients Quantity (mg) %(VW
Lansoprazole
(As enteric coated pellets) (8.5%) 177 54.5
Ondansetron
(As pellets) (4%) 100 30.8
Dummy pellets 48 14.8
Capsule target weight 325 -
Empty hard gelatin capsules 1No's _
Example 62
(S)-lansoprazole (30mg)(EC) and Ondansetron (4mg) capsules:
Ingredients Quantity (mg) %(W/W)
(S)-Iansoprazole
(As enteric coated pellets) (8.5%) 354 78 Ondansetron
(As pellets) (4%) 100 22
Capsule target weight 454
Empty hard gelatin capsules 1 No's
Example 63
Omeprazole (10mg)(EC) and dόmperidone (30mg)(SR) capsules:
Ingredients Quantity (mg) %(W/W)
Omeprazole
(As enteric coated pellets) (8.5%) 118 47.2 Domperidone
(As sustained release pellets) (24%) 125 50
Dummy pellets 7 2.8
Capsule target weight 250
Empty hard gelatin capsules 1 No's
Example 64
Omeprazole (20mg)(EC) and domperidone (30mg)(SR) capsules: Ingredients Quantity (mg) %(W/W)
Omeprazole
(As enteric coated pellets) (8.5%) 236 65.4
Domperidone
(As sustained release pellets) (24%) 125 34.6
Capsule target weight 361
Empty hard gelatin capsules 1 No's
Example 65 Omeprazole (10mg)(EC) and domperidone (10mg) capsules:
Ingredients Quantity (mg) %(W/W)
Omeprazole
(As enteric coated pellets) (8.5%) 118 47.2
Domperidone
(As pellets) (12%) 84 33.6
Dummy pellets 48 19.2
Capsule target weight 250 -
Empty hard gelatin capsules 1No's -
Example 66 Omeprazole (20mg)(EC) and domperidone (10mg) capsules:
Ingredients Quantity (mg) %(W/
Omeprazole
(As enteric coated pellets) (8.5%) 236 67.4
Domperidone
(As pellets) (12%) 84 24
Dummy pellets 30 8.57
Capsule target weight 350 -
Empty hard gelatin capsules 1No's _
Example 67 Omeprazole (10mg)(EC) and itopride hydrochloride (150mg)(SR) capsules: Ingredients Quantity (mg) %(W/W)
Omeprazole
(As enteric coated pellets) (8.5%) 118 32.8
Itopride hydrochloride
(As sustained release pellets) (64%) 235 65.3
Dummy pellets 7 1.94
Capsule target weight 360 -
Empty hard gelatin capsules 1 No's -
Example 68 Omeprazole (20mg)(EC) and itopride hydrochloride (150mg)(SR) capsules:
Ingredients Quantity (mg) %(V\
Omeprazole (As enteric coated pellets) (8.5%) 236 47.1
Itopride hydrochloride
(As sustained release pellets) (64%) 235 46.9
Dummy pellets 30 5.99
Capsule target weight 501 - Empty hard gelatin capsules 1 No's -
Example 69 Omeprazole (10mg)(EC) and itopride hydrochloride (50mg) capsules:
Ingredients Quantity (mg) %(WΛ Omeprazole
(As enteric coated pellets) (8.5%) 118 42.1
Itopride hydrochloride
(As pellets) (32%) 157 56.1
Dummy pellets 5 1.79 Capsule target weight 280 -
Empty hard gelatin capsules 1 No's -
Example 70
Omeprazole (20mg)(EC) and itopride hydrochloride (50mg) capsules: Ingredients Quantity (mg) %(W/W)
Omeprazole
(As enteric coated pellets) (8.5%) 236 57.6
Itopride hydrochloride (As pellets) (32%) 157 38.3
Dummy pellets 17 4.15
Capsule target weight 410
Empty hard gelatin capsules 1 No's
Example 71 Omeprazole (10mg)(EC) and mosapride citrate (15mg)(SR) capsules:
Ingredients Quantity (mg) %c
Omeprazole
(As enteric coated pellets) (8.5%) 118 47.
Mosapride citrate dihydrate
Eq.to mosapride citrate
(As sustained release pellets) (12%) 125 50
Dummy pellets 7 2.8
Capsule target weight 250 -
Empty hard gelatin capsules 1 No's _
Example 72 Omeprazole (20mg)(EC) and mosapride citrate (15mg)(SR) capsules:
Ingredients Quantity (mg) %(VM
Omeprazole
(As enteric coated pellets) (8.5%) 236 58.9
Mosapride citrate dihydrate
Eq.to mosapride citrate
(As sustained release pellets) (12%) 125 31.2
Dummy pellets 40 2.8
Capsule target weight 401 -
Empty hard gelatin capsules 1 No's -
Example 73 Omeprazole (10mg)(EC) and mosapride citrate (5mg) capsules:
Ingredients Quantity (mg) %(W/W)
Omeprazole
(As enteric coated pellets) (8.5%) 118 47.2
Mosapride citrate dihydrate
Eq. to mosapπde citrate
(As pellets) (6%) 84 33.6
Dummy pellets 48 19.2
Capsule target weight 250 - Empty hard gelatin capsules 1 No's
Example 74 Omeprazole (20mg)(EC) and mosapride citrate (5mg) capsules:
Ingredients Quantity (mg) %(VW
Omeprazole
(As enteric coated pellets) (8.5%) 236 67.4
Mosapride citrate dihydrate
Eq. to mosapride citrate
(As pellets) (6%) 84 24
Dummy pellets 30 8.57
Capsule target weight 350 -
Empty hard gelatin capsules 1 No's -
Example 75 Omeprazole (10mg)(EC) and ondansetron (12mg)(SR) capsules:
Ingredients Quantity (mg) %(W
Omeprazole
(As enteric coated pellets) (8.5%) 118 47.2
Ondansetron
(As sustained release pellets) (12%) 100 40
Dummy pellets 32 12.8
Capsule target weight 250 -
Empty hard gelatin capsules 1 No's -
Example 76
Omeprazole (20mg)(EC) and ondansetron (12mg)(SR) capsules: Ingredients Quantity (mg) %(W/W)
Omeprazole
(As enteric coated pellets) (8.5%) 236 .67.4
Ondansetron
(As sustained release pellets) (12%) • 100 28.6
Dummy pellets 14 4
Capsule target weight 350
Empty hard gelatin capsules 1 No's
Example 77 Omeprazole (10mg)(EC) and ondansetron (4mg) capsules:
Ingredients Quantity (mg) %(W/W)
Omeprazole
(As enteric coated pellets) (8.5%) 118 47.2
Ondansetron
(As pellets) (4%) 100 40
Dummy pellets 32 12.8
Capsule target weight 250
Empty hard gelatin capsules 1No's Example 78 Omeprazole (20mg)(EC) and ondansetron (4mg) capsules:
Ingredients Quantity (mg) %(W/W)
Omeprazole
(As enteric coated pellets) (8.5%) 236 67.4
Ondansetron
( (AAss ppeelllleettss)) ((44%%)) 100 28.6
D Duummmmyy ppeelllleettss 14 4
C Caappssuullee ttaarrggeett wweeiigghhtt 350 -
E Emmppttyy hhaarrdd ggeellaattiinn ccaappssuulleess 1 No's -
Example 79
Esomeprazole (20mg)(EC) and domperidone (30mg)(SR) capsules:
Ingredients Quantity (mg) %(W/W)
Esomeprazole magnesium trihydrate
Eq. to esomeprazole
(As enteric coated pellets) (13%) 155 42.5
Domperidone
(As sustained release pellets) (24%) 125 34.2
Dummy pellets 85 23.3
Capsule target weight 365
Empty hard gelatin capsules 1 No's
Example 80 Esomeprazole (40mg)(EC) and domperidone (30mg)(SR) capsules:
Ingredients Quantity (mg) %(W/1
Esomeprazole magnesium trihydrate
Eq .to esomeprazole
(As enteric coated pellets) (13%) 310 60.8
Domperidone
(As sustained release pellets) (24%) 125 24.5
Dummy pellets 75 14.7
Capsule target weight 510 -
Empty hard gelatin capsules 1No's -
Example 81
Esomeprazole (20mg)(EC) and domperidone (10mg) capsules:
Ingredients Quantity (mg) %(WΛ
Esomeprazole magnesium trihydrate
Eq. to esomeprazole
(As enteric coated pellets) (13%) 155 62
Domperidone
(As pellets) (12%) 84 33.6
Dummy pellets 11 4.4
Capsule target weight 250 -
Empty hard gelatin capsules 1No's - Example 82
Esomeprazole (40mg)(EC) and domperidone (10mg) capsules: Ingredients Quantity (mg) %(W/W)
Esomeprazole magnesium trihydrate Eq .to esomeprazole (As enteric coated pellets) (13%) 310 68.9
Domperidone
(As pellets) (12%) 84 18.7
Dummy pellets 56 12.4
Capsule target weight 450
Empty hard gelatin capsules 1 No's
Example 83 Esomeprazole (20mg)(EC) and itopride hydrochloride (150mg)(SR) capsules:
Ingredients Quantity (mg) %(W/W)
Esomeprazole magnesium trihydrate
Eq. to esomeprazole
(As enteric coated pellets) (13%) 155 34.4
Itopride hydrochloride
(As sustained release, pellets) (64%) 235 52.2
Dummy pellets 60 13.3
Capsule target weight 450 -
Empty hard gelatin capsules 1 No's -
Example 84
Esomeprazole (40mg)(EC) and itopride I hydrochloride (150mg)(SR) capsules
Ingredients Quantity (mg) %(W/W)
Esomeprazole magnesium trihydrate
Eq. to esomeprazole
(As enteric coated pellets) (13%) 310 56.9
Itopride hydrochloride (As sustained release pellets) (64%) 235 43.1
Capsule target weight 545
Empty hard gelatin capsules 1 No's
Example 85
Esomeprazole (20mg)(EC) and itopride hydrochloride (50mg) capsules: Ingredients Quantity (mg) %(W/W)
Esomeprazole magnesium trihydrate
Eq .to esomeprazole
(As enteric coated pellets) (13%) 155 44.3
Itopride hydrochloride (As pellets) (32%) 157 44.9
Dummy pellets 38 10.9
Capsule target weight 350 -
Empty hard gelatin capsules 1 No's -
Example 86
Esomeprazole (40mg)(EC) and itopride hydrochloride (50mg) capsules:
Ingredients Quantity (mg) %(W/W)
Esomeprazole magnesium trihydrate
Eq .to esomeprazole (As enteric coated pellets) (13%) 310 66.4
Itopride hydrochloride
(As pellets) (32%) 157 33.6
Capsule target weight 467
Empty hard gelatin capsules 1 No's Example 87
Esomeprazole (20mg)(EC) and mosapride citrate (15mg)(SR) capsules:
Ingredients Quantity (mg) %(W/W)
Esomeprazole magnesium trihydrate
Eq .to esomeprazole (As enteric coated pellets) (13%) 155 47
Mosapride citrate dihydrate
Eq .to mosapride citrate
(As sustained release pellets) (12%) 125 37.9
Dummy pellets 50 15.2
Capsule target weight 330
Empty hard gelatin capsules 1 No's
Example 88
Esomeprazole (40mg)(EC) and mosapride citrate (15mg
Ingredients Quantity (mg) %(W/W)
Esomeprazole magnesium trihydrate
Eq .to esomeprazole
(As enteric coated pellets) (13%) 310 68.9
Mosapride citrate dihydrate
Eq.to mosapride citrate
( (AAss ssuussttaaiinneedd rreelleeaassee p peelllleettss)) ( (1122%%)) 112255 27.8
Dummy pellets 15 3.33
Capsule target weight 450
Empty hard gelatin capsules 1No's
Example 89
Esomeprazole (20mg)(EC) and mosapride citrate (5mg) capsules:
Ingredients Quantity (mg) %(W/W)
Esomeprazole magnesium trihydrate
Eq.to esomeprazole (As enteric coated pellets) (13%) 155 62
Mosapride citrate dihydrate
Eq.to mosapride citrate
(As pellets) (6%) 84 33.6
Dummy pellets 11 4.4 Capsule target weight 250
Empty hard gelatin capsules 1 No's
Example 90
Esomeprazole (40mg)(EC) and mosapride citrate (5mg) capsules:
Ingredients Quantity (mg) %(W/W) Esomeprazole magnesium trihydrate
Eq.to esomeprazole
(As enteric coated pellets) (13%) 310 68.9
Mosapride citrate dihydrate
Eq.to mosapride citrate (As pellets) (6%) 125 27.8
Dummy pellets 15 3.33
Capsule target weight 450
Empty hard gelatin capsules 1 No's
Example 91 Esomeprazole (20mg)(EC) and ondansetron (12mg)(SR) capsules:
Ingredients Quantity (mg) %(W/W)
Esomeprazole magnesium trihydrate
Eq.to esomeprazole
(As enteric coated pellets) (13%) 155 60.8 Ondansetron
(As sustained release pellets) (12%) 100 39.2
Capsule target weight 255
Empty hard gelatin capsules 1 No's
Example 92 Esomeprazole (40mg)(EC) and ondansetron (12mg)(SR) capsules:
Ingredients Quantity (mg) %(W/V
Esomeprazole magnesium trihydrate
Eq .to esomeprazole
(As enteric coated pellets) (13%) 310 72.9
Ondansetron
(As sustained release pellets) (12%) 100 23.5
Dummy pellets 15 3.53
Capsule target weight 425 -
Empty hard gelatin capsules 1No's -
Example 93
Esomeprazole (20mg)(EC) and ondansetron (4mg) capsules:
Ingredients Quantity (mg) %(V\
Esomeprazole magnesium trihydrate
Eq. to esomeprazole
(As enteric coated pellets) (13%) 155 60.8
Ondansetron
(As pellets) (4%) 100 39.2
Capsule target weight 255 -
Empty hard gelatin capsules 1 No's -
Example 94
Esomeprazole (40mg)(EC) and ondansetron (4mg) capsules:
Ingredients Quantity (mg) %(V\
Esomeprazole magnesium trihydrate
Eq .to esomeprazole
(As enteric coated pellets) (13%) 310 72.9
Ondansetron
(As pellets) (4%) 100 23.5
Dummy pellets 15 3.53
Capsule target weight 425 -
Empty hard gelatin capsules 1 No1S -
Claims
1. A stable pharmaceutical formulations for hygroscopic antiulcerative substituted benzimidazoles, optionally in combination with other active pharmaceutical ingredients, which comprises substituted benzimidazoles selected from pantoprazole, rabeprazole, omeprazole, lansoprazole, tenatoprazole, esomeprazole, (S)-pantoprazole, (S)-rabeprazole and (S)- lansoprazole or a salt thereof; other active pharmaceutical ingredients selected from domperidone, itopride hydrochloride, mosapride citrate and ondansetron; stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide, heavy sodium carbonate, light calcium carbonate, light magnesium carbonate, light magnesium oxide and light sodium carbonate; and mannitol.
2. The formulation as claimed in claim 1 , wherein substituted benzimidazoles selected from pantoprazole, rabeprazole, omeprazole, lansoprazole, tenatoprazole, esomeprazole, (S)-pantoprazoIe, (S)-rabeprazole and (S)- lansoprazole or a salt thereof in the range of 3 to 70% by weight; other active pharmaceutical . ingredients selected from domperidone, itopride hydrochloride, mosapride citrate and ondansetron in the range of 10 to 90% by weight; stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide, heavy sodium carbonate, light calcium carbonate, light magnesium carbonate, light magnesium oxide and light sodium carbonate in the range of 0.5 to 90% by weight and mannitol in the range of 9 to 80% by weight, based on the total weight of pharmaceutical formulations.
3. The formulation as claimed in claim 2, wherein substituted benzimidazoles selected from pantoprazole, rabeprazole, omeprazole, lansoprazole, tenatoprazole, esomeprazole, (S)-pantoprazole, (S)-rabeprazole and (S)- lansoprazole or a salt thereof in the range of 8 to 65% by weight; other active pharmaceutical ingredients selected from domperidone, itopride hydrochloride, mosapride citrate and ondansetron in the range of 20 to 70% by weight; stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide, heavy sodium carbonate, light calcium carbonate, light magnesium carbonate, light magnesium oxide
and light sodium carbonate in the range of 5 to 60% by weight and mannitol in the range of 15 to 75% by weight, based on the total weight of pharmaceutical formulations.
4. The formulation as claimed in claim 1 , wherein the said formulation is in the form of a tablet, a caplet, pellets, a capsule, granules, a pill, powder or a sachet.
5. The formulation as claimed in claim 1 , wherein antiulcerative substituted benzimidazoles selected from pantoprazole, rabeprazole, omeprazole, lansoprazole, esomeprazole, tenatoprazole, (S)-pantoprazole, (S)- rabeprazole and (S)-Iansoprazole or a salt thereof are enteric coated pellets or tablets; other active pharmaceutical ingredients selected from domperidone, itopride hydrochloride, mosapride citrate and ondansetron are sustained release pellets or pellets.
6. The formulation as claimed in claim 5, wherein the said formulation is in the form of enteric-coated tablets.
7. The formulation as claimed in claim 6, wherein the enteric-coated tablet selected from rabeprazole sodium is 10 mg.
8. The formulation as claimed in claim 6, wherein the enteric-coated tablet selected from rabeprazole sodium is 20 mg.
9. The formulation as claimed in claim 6, wherein the enteric-coated tablet selected from pantoprazole is 20 mg.
10. The formulation as claimed in claim 6, wherein the enteric-coated tablets selected from pantoprazole is 40 mg.
11. The formulation as claimed in claim 6, wherein the enteric-coated tablet selected from esomeprazole is 20 mg.
12. The formulation as claimed in claim 6, wherein the enteric-coated tablet selected from esomeprazole is 40 mg.
13. The formulation as claimed in claim 5, the said formulation is in the form of capsules.
14. The formulation as claimed in claim 13, wherein the capsule is selected from powder, tablet, compressed powder, pellets or the granules.
15. The formulation as claimed in claim 14, the said formulation is in the form of a pellet.
16. The formulation as claimed in claim 15, wherein the capsule is selected from rabeprazole sodium (EC) 10 mg and domperidone (SR) 30 mg.
17. The formulation as claimed in claim 15, wherein the capsule is selected from rabeprazole sodium (EC) 20 mg and domperidone (SR) 30 mg.
18. The formulation as claimed in claim 15, wherein the capsule is selected from rabeprazole sodium (EC) 10 mg and domperidone 10 mg.
19. The formulation as claimed in claim 15, wherein the capsule is selected from rabeprazole sodium (EC) 20 mg and domperidone 10 mg.
20. The formulation as claimed in claim 15, wherein the capsule is selected from rabeprazole sodium (EC) 10 mg and itopride hydrochloride (SR) 150 mg.
21. The formulation as claimed in claim 15, wherein the capsule is selected from rabeprazole sodium (EC) 20 mg and itopride hydrochloride (SR) 150 mg.
22. The formulation as claimed in claim 15, wherein the capsule is selected from rabeprazole sodium (EC) 10 mg and itopride hydrochloride 50 mg.
23. The formulation as claimed in claim 15, wherein the capsule is selected from rabeprazole sodium (EC) 20 mg and itopride hydrochloride 50 mg.
24. The formulation as claimed in claim 15, wherein the capsule is selected from rabeprazole sodium (EC) 10 mg and mosapride citrate (SR) 15 mg.
25. The formulation as claimed in claim 15, wherein the capsule is selected from rabeprazole sodium (EC) 20 mg and mosapride citrate (SR) 15 mg.
26. The formulation as claimed in claim 15, wherein the capsule is selected from rabeprazole sodium (EC) 10 mg and mosapride citrate 5 mg.
27. The formulation as claimed in claim 15, wherein the capsule is selected from rabeprazole sodium (EC) 20 mg and mosapride citrate 5 mg.
28. The formulation as claimed in claim 15, wherein the capsule is selected from rabeprazole sodium (EC) 10 mg and ondansetron (SR) 12 mg.
29. The formulation as claimed in claim 15, wherein the capsule is selected from rabeprazole sodium (EC) 20 mg and ondansetron (SR) 12 mg.
30. The formulation as claimed in claim 15, wherein the capsule is selected from rabeprazole sodium (EC) 10 mg and ondansetron 4 mg.
31. The formulation as claimed in claim 15, wherein the capsule is selected from rabeprazole sodium (EC) 20 mg and ondansetron 4 mg.
32. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-rabeprazole sodium (EC) 10 mg and domperidone (SR) 30 mg.
33. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-rabeprazole sodium (EC) 20 mg and domperidone (SR) 30 mg.
34. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-rabeprazole sodium (EC) 10 mg and domperidone 10 mg.
35. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-rabeprazole sodium (EC) 20 mg and domperidone 10 mg.
36. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-rabeprazole sodium (EC) 10 mg and itopride hydrochloride (SR)
150 mg.
37. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-rabeprazole sodium (EC) 20 mg and itopride hydrochloride (SR) 150 mg.
38. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-rabeprazole sodium (EC) 10 mg and itopride hydrochloride 50 mg.
39. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-rabeprazole sodium (EC) 20 mg and itopride hydrochloride 50 mg.
40. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-rabeprazole sodium (EC) 10 mg and mosapride citrate (SR) 15 mg.
41. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-rabeprazoIe sodium (EC) 20 mg and mosapride citrate (SR) 15 mg.
42. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-rabeprazole sodium (EC) 10 mg and mosapride citrate 5 mg.
43. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-rabeprazole sodium (EC) 20 mg and mosapride citrate 5 mg.
44. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-rabeprazole sodium (EC) 10 mg and ondansetron (SR) 12 mg.
45. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-rabeprazole sodium (EC) 20 mg and ondansetron (SR) 12 mg.
46. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-rabeprazole sodium (EC) 10 mg and ondansetron 4 mg.
47. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-rabeprazole sodium (EC) 20 mg and ondansetron 4 mg.
48. The formulation as claimed in claim 15, wherein the capsule is selected from pantoprazole (EC) 20 mg and domperidone (SR) 30 mg.
49. The formulation as claimed in claim 15, wherein the capsule is selected from pantoprazole (EC) 40 mg and domperidone (SR) 30 mg.
50. The formulation as claimed in claim 15, wherein the capsule is selected from pantoprazole (EC) 20 mg and domperidone 10 mg.
51. The formulation as claimed in claim 15, wherein the capsule is selected from pantoprazole (EC) 40 mg and domperidone 10 mg.
52. The formulation as claimed in claim 15, wherein the capsule is selected from pantoprazole (EC) 20 mg and itopride hydrochloride (SR) 150 mg.
53. The formulation as claimed in claim 15, wherein the capsule is selected from pantoprazole (EC) 40 mg and itopride hydrochloride (SR) 150 mg.
54. The formulation as claimed in claim 15, wherein the capsule is selected from pantoprazole (EC) 20 mg and itopride hydrochloride 50 mg.
55. The formulation as claimed in claim 15, wherein the capsule is selected from pantoprazole (EC) 40 mg and itopride hydrochloride 50 mg.
56. The formulation as claimed in claim 15, wherein the capsule is selected from pantoprazole (EC) 20 mg and mosapride citrate (SR) 15 mg.
57. The formulation as claimed in claim 15, wherein the capsule is selected from pantoprazole (EC) 40 mg and mosapride citrate (SR) 15 mg.
58. The formulation as claimed in claim 15, wherein the capsule is selected from pantoprazole (EC) 20 mg and mosapride citrate 5 mg.
59. The formulation as claimed in claim 15, wherein the capsule is selected from pantoprazole (EC) 40 mg and mosapride citrate 5 mg.
60. The formulation as claimed in claim 15, wherein the capsule is selected from pantoprazole (EC) 20 mg and ondansetron (SR) 12 mg.
61. The formulation as claimed in claim 15, wherein the capsule is selected from pantoprazole (EC) 40 mg and ondansetron (SR) 12 mg.
62. The formulation as claimed in claim 15, wherein the capsule is selected from pantoprazole (EC) 20 mg and ondansetron 4 mg.
63. The formulation as claimed in claim 15, wherein the capsule is selected from pantoprazole (EC) 40 mg and ondansetron 4 mg.
64. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-pantoprazole (EC) 20 mg and domperidone (SR) 30 mg.
65. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-pantoprazole (EC) 40 mg and domperidone (SR) 30 mg.
66. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-pantoprazole (EC) 20 mg and domperidone 10 mg.
67. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-pantoprazole (EC) 40 mg and domperidone 10 mg.
68. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-pantoprazole (EC) 20 mg and itopride hydrochloride (SR) 150 mg.
69. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-pantoprazole (EC) 40 mg and itopride hydrochloride (SR) 150 mg.
70. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-pantoprazole (EC) 20 mg and itopride hydrochloride 50 mg.
71. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-pantoprazole (EC) 40 mg and itopride hydrochloride 50 mg.
72. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-pantoprazole (EC) 20 mg and mosapride citrate (SR) 15 mg.
73. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-pantoprazole (EC) 40 mg and mosapride citrate (SR) 15 mg.
74. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-pantoprazole (EC) 20 mg and mosapride citrate 5 mg.
75. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-pantoprazole (EC) 40 mg and mosapride citrate 5 mg.
76. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-pantoprazoIe (EC) 20 mg and ondansetron (SR) 12 mg.
77. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-pantoprazole (EC) 40 mg and ondansetron (SR) 12 mg.
78. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-pantoprazole (EC) 20 mg and ondansetron 4 mg.
79. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-pantoprazole (EC) 40 mg and ondansetron 4 mg.
80. The formulation as claimed in claim 15, wherein the capsule is selected from omeprazole (EC) 10 mg and domperidone (SR) 30 mg.
81. The formulation as claimed in claim 15, wherein the capsule is selected from omeprazole (EC) 20 mg and domperidone (SR) 30 mg.
82. The formulation as claimed in claim 15, wherein the capsule is selected from omeprazole (EC) 10 mg and domperidone 10 mg.
83. The formulation as claimed in claim 15, wherein the capsule is selected from omeprazole (EC) 20 mg and domperidone 10 mg.
84. The formulation as claimed in claim 15, wherein the capsule is selected from omeprazole (EC) 10 mg and itopride hydrochloride (SR) 150 mg.
85. The formulation as claimed in claim 15, wherein the capsule is selected from omeprazole (EC) 20 mg and itopride hydrochloride (SR) 150 mg.
86. The formulation as claimed in claim 15, wherein the capsule is selected from omeprazole (EC) 10 mg and itopride hydrochloride 50 mg.
87. The formulation as claimed in claim 15, wherein the capsule is selected from omeprazole (EC) 20 mg and itopride hydrochloride 50 mg.
88. The formulation as claimed in claim 15, wherein the capsule is selected from omeprazole (EC) 10 mg and mosapride citrate (SR) 15 mg.
89. The formulation as claimed in claim 15, wherein the capsule is selected from omeprazole (EC) 20 mg and mosapride citrate (SR) 15 mg.
90. The formulation as claimed in claim 15, wherein the capsule is selected from omeprazole (EC) 10 mg and mosapride citrate 5 mg.
91. The formulation as claimed in claim 15, wherein the capsule is selected from omeprazole (EC) 20 mg and mosapride citrate 5 mg.
92. The formulation as claimed in claim 15, wherein the capsule is selected from omeprazole (EC) 10 mg and ondansetron (SR) 12 mg.
93. The formulation as claimed in claim 15, wherein the capsule is selected from omeprazole (EC) 20 mg and ondansetron (SR) 12 mg.
94. The formulation as claimed in claim 15, wherein the capsule is selected from omeprazole (EC) 10 mg and ondansetron 4 mg.
95. The formulation as claimed in claim 15, wherein the capsule is selected from omeprazole (EC) 20 mg and ondansetron 4 mg.
96. The formulation as claimed in claim 15, wherein the capsule is selected from lansoprazole (EC) 15 mg and domperidone (SR) 30 mg.
97. The formulation as claimed in claim 15, wherein the capsule is selected from lansoprazole (EC) 30 mg and domperidone (SR) 30 mg.
98. The formulation as claimed in claim 15, wherein the capsule is selected from lansoprazole (EC) 15 mg and domperidone 10 mg.
99. The formulation as claimed in claim 15, wherein the capsule is selected from lansoprazole (EC) 30 mg and domperidone 10 mg.
100. The formulation as claimed in claim 15, wherein the capsule is selected from lansoprazole (EC) 15 mg and itopride hydrochloride (SR) 150 mg.
101. The formulation as claimed in claim 15, wherein the capsule is selected from lansoprazole (EC) is 30 mg and itopride hydrochloride (SR) 150 mg.
102. The formulation as claimed in claim 15, wherein the capsule is selected from lansoprazole (EC) 15 mg and itopride hydrochloride 50 mg.
103. The formulation as claimed in claim 15, wherein the capsule is selected from lansoprazole (EC) 30 mg and itopride hydrochloride 50 mg.
104. The formulation as claimed in claim 15, wherein the capsule is selected from lansoprazole (EC) 15 mg and mosapride citrate (SR) 15 mg.
105. The formulation as claimed in claim 15, wherein the capsule is selected from lansoprazole (EC) 30 mg and mosapride citrate (SR) 15 mg.
106. The formulation as claimed in claim 15, wherein the capsule is selected from lansoprazole (EC) 15 mg and mosapride citrate 5 mg.
107. The formulation as claimed in claim 15, wherein the capsule is selected from lansoprazole (EC) 30 mg and mosapride citrate 5 mg.
108. The formulation as claimed in claim 15, wherein the capsule is selected from lansoprazole (EC) 15 mg and ondansetron (SR) 12 mg.
109. The formulation as claimed in claim 15, wherein the capsule is selected from lansoprazole (EC) 30 mg and ondansetron (SR) 12 mg.
110. The formulation as claimed in claim 15, wherein the capsule is selected from lansoprazole (EC) 15 mg and ondansetron 4 mg.
111. The formulation as claimed in claim 15, wherein the capsule is selected from lansoprazole (EC) 30 mg and ondansetron 4 mg.
112. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-lansoprazole (EC) 15 mg and domperidone (SR) 30 mg.
113. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-lansoprazole (EC) 30 mg and domperidone (SR) 30 mg.
114. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-lansoprazole (EC) 15 mg and domperidone 10 mg.
115. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-lansoprazole (EC) 30 mg and domperidone 10 mg.
116. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-lansoprazole (EC) 15 mg and itopride hydrochloride (SR) 150 mg.
117. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-lansoprazole (EC) 30 mg and itopride hydrochloride (SR) 150 mg.
118. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-lansoprazole (EC) 15 mg and itopride hydrochloride 50 mg.
119. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-lansoprazole (EC) 30 mg and itopride hydrochloride 50 mg.
120. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-lansoprazole (EC) 15 mg and mosapride citrate (SR) 15 mg.
121. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-lansoprazole (EC) 30 mg and mosapride citrate (SR) 15 mg.
122. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-lansoprazole (EC) 15 mg and mosapride citrate 5 mg.
123. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-lansoprazole (EC) 30 mg and mosapride citrate 5 mg.
124. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-lansoprazole (EC) 15 mg and ondansetron (SR) 12 mg.
125. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-lansoprazole (EC) 30 mg and ondansetron (SR) 12 mg.
126. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-lansoprazole (EC) 15 mg and ondansetron 4 mg.
127. The formulation as claimed in claim 15, wherein the capsule is selected from (S)-Iansoprazole (EC) 30 mg and ondansetron 4 mg.
128. The formulation as claimed in claim 15, wherein the capsule is selected from esomeprazole (EC) 20 mg and domperidone (SR) 30 mg.
129. The formulation as claimed in claim 15, wherein the capsule is selected from esomeprazole (EC) 40 mg and domperidone (SR) 30 mg.
130. The formulation as claimed in claim 15, wherein the capsule is selected from esomeprazole (EC) 20 mg and domperidone 10 mg.
131. The formulation as claimed in claim 15, wherein the capsule is selected from esomeprazole (EC) 40 mg and domperidone 10 mg.
132. The formulation as claimed in claim 15, wherein the capsule is selected from esomeprazole (EC) 20 mg and itopride hydrochloride (SR) 150 mg.
133. The formulation as claimed in claim 15, wherein the capsule is selected from esomeprazole (EC) 40 mg and itopride hydrochloride (SR) 150 mg.
134. The formulation as claimed in claim 15, wherein the capsule is selected from esomeprazole (EC) 20 mg and itopride hydrochloride 50 mg.
135. The formulation as claimed in claim 15, wherein the capsule is selected from esomeprazole (EC) 40 mg and itopride hydrochloride 50 mg.
136. The formulation as claimed in claim 15, wherein the capsule is selected from esomeprazole (EC) 20 mg and mosapride citrate (SR) 15 mg.
137. The formulation as claimed in claim 15, wherein the capsule is selected from esomeprazole (EC) 40 mg and mosapride citrate (SR) 15 mg.
138. The formulation as claimed in claim 15, wherein the capsule is selected from esomeprazole (EC) 20 mg and mosapride citrate 5 mg.
139. The formulation as claimed in claim 15, wherein the capsule is selected from esomeprazole (EC) 40 mg and mosapride citrate 5 mg.
140. The formulation as claimed in claim 15, wherein the capsule is selected from esomeprazole (EC) 20 mg and ondansetron (SR) 12 mg.
141. The formulation as claimed in claim 15, wherein the capsule is selected from esomeprazole (EC) 40 mg and ondansetron (SR) 12 mg.
142. The formulation as claimed in claim 15, wherein the capsule is selected from esomeprazole (EC) 20 mg and ondansetron 4 mg.
143. The formulation as claimed in claim 15, wherein the capsule is selected from esomeprazole (EC) 40 mg and ondansetron 4 mg.
144. The formulation as claimed in claim 1 , wherein at least one additional excipient is used.
145. The formulation as claimed in claim 144, wherein the additional excipient is selected from pharmaceutical disintegrants, binders, lubricants, glidants, fillers or diluents, stabilizing agents, seal coating materials, enteric coating materials, plasticizers, anti-adherents, colorants, and a mixture thereof.
146. The formulation as claimed in claim 145, wherein the disintegrator is selected from starch, croscarmellose sodium, crospovidone, carboxymethylcellulose calcium, carboxymethylcellulose sodium and magnesium aluminium silicate; and a mixture thereof.
147. The formulation as claimed in claim 145, wherein the binder is selected from hydroxypropyl cellulose, polyvinylpyrrolidone k-30, hydroxypropyl cellulose (low-substituted) and starch; and a mixture thereof.
148. The formulation as claimed in claim 145, wherein the lubricant is selected from stearic acid, a salt of stearic acid, talc, sodium stearyl fumarate, glyceryl behenate, magnesium silicate, magnesium trisilicate and hydrogenated castor oil; and a mixture thereof.
149. The formulation as claimed in claim 145, wherein the glidant is selected from colloidal anhydrous silica and talc; and a mixture thereof.
150. The formulation as claimed in claim 145, wherein the filler is selected from calcium carbonate, dibasic calcium phosphate, lactose, magnesium carbonate, sucrose, starch, magnesium oxide, lactose anhydrous, microcrystalline cellulose and mannitol; and a mixture thereof.
151. The formulation as claimed in claim 145, wherein the stabilizing agents is selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide, heavy sodium carbonate, light calcium carbonate, light magnesium carbonate, light magnesium oxide, light sodium carbonate; or a mixtures thereof.
152. The formulation as claimed in claim 145, wherein the seal coating materials is selected from hydroxypropylcellulose, alginate derivatives, hydroxypropylmethylcellulose, carboxymethylcellulose, polyvinylpyrrolidone derivatives, organic white; or a mixture thereof.
153. The formulation as claimed in claim 145, wherein the enteric coating materials is selected from cellulose acetate phthalate, ' hydroxypropylmethylcellulose phthalate and methacrylic acid derivatives such as eudragit L 100-55, eudragit L30 D-55, opadry enteric; or a mixture thereof.
154. The formulation as claimed in claim 145, wherein the plasticizer is selected from cetyl alcohol, stearyl alcohol or phthalate derivatives such as diethyl phthalate, dipropyl phthalate, dibutyl phthalate, dioctyl phthalate or polyethleneglycol derivatives; or a mixture thereof.
155. The formulation as claimed in claim 145, wherein the anti-adherents is selected from talc, starch, stearic acid, hydrogenated castor oil; or a mixture thereof.
156. The formulation as claimed in claim 144, wherein the excipient selection depends on various factors, such as, the choice of active ingredient percentage, the objectives of the tablet formulation development and method of manufacture.
157. The formulation as claimed in claim 5, wherein the antiulcerative substituted benzimidazole is rabeprazole sodium or (S)-rabeprazole sodium; stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide, heavy sodium carbonate, light magnesium oxide, light calcium carbonate, light magnesium carbonate and light sodium carbonate; mannitol, starch, polyvinylpyrrolidone s-630, hydroxypropylcellulose or hydroxypropyl cellulose (low-substituted); ethanol, mannitol, sodium stearyl fumarate, hydroxypropylmethylcellulose- 15cps, acryl EZE, opadry organic and opadry enteric.
158. The formulation as claimed in claim 157, wherein rabeprazole sodium in the range of 3 to 23% by weight, light magnesium oxide in the range of 0.5 to 2.5% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium. carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 25 to 78% by weight, mannitol in the range of 9 to 80% by weight, polyvinylpyrrolidone s-630 in the range of 0.5 to 4% by weight, starch in the range of 0.5 to 2.5% by weight, hydroxypropylcellulose
(low-substituted) or hydroxypropylcellulose in the range of 0.5 to 23% by weight, sodium stearyl fumarate in the range of 0.5 to 2.5% by weight, hydroxypropylmethylcellulose-15cps in the range of 2.5 to 15% by weight, acryl EZE in the range of 7 to 28% by weight, opadry organic white in the range of 3 to 10% by weight and opadry enteric pink in the range of 7 to
17% by weight, based on the total weight of pharmaceutical dosage form.
159. The formulation as claimed in claim 158, wherein rabeprazole sodium in the range of 6 to 14% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 43 to 60% by weight; mannitol in the range of 16 to 21 % by weight, polyvinylpyrrolidone s-630 in the range of 1.5 to 2.5% by weight, starch in the range of 1 to 2% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose in the range of 13 to 17% by weight, sodium stearyl fumarate in the range of 1 to
2% by weight, hydroxypropylmethylcellulose-iδcps in the range of 4.5 to 5.5% by weight and acryl EZE in the range of 13 to 17 % by weight, based on the total weight of enteric coated tablets
160. The formulation as claimed in claim 159, wherein rabeprazole sodium is 7.69% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 53.8% by weight; mannitol is 18.5% by weight, polyvinylpyrrolidone s-630 is 1.92% by weight, starch is 1.15% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose is 15.4% by weight, sodium stearyl fumarate is 1.54% by weight, hydroxypropylmethylcellulose-15cps is 5% by weight and acryl EZE is 14.7% by weight, based on the total weight of enteric coated tablets.
161. The formulation as claimed in claim 159, wherein rabeprazole sodium is 12.5% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 48.8% by weight; mannitol is 18.8% by weight, polyvinylpyrrolidone s-630 is 2.19% by weight, starch is 1.25% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose is 15% by weight, sodium stearyl fumarate is 1.56% by weight, hydroxypropylmethylcellulose-iδcps is 5% by weight and acryl EZE is
14.7% by weight, based on the total weight of enteric coated tablets.
162. The formulation as claimed in claim 158, wherein rabeprazole sodium in the range of 6 to 9% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 46 to 58% by weight, light magnesium oxide in the range of 1 to 2% by weight; mannitol in the range of 16 to 77% by weight, polyvinylpyrrolidone s-630 in the range of 1.5 to 2.5% by weight, starch in the range of 1 to 1.5% by weight, hydroxypropylmethylcellulose-15cps in the range of 6 to 8% by weight, acryl EZE in the range of 10 to 14% by weight, opadry organic white in the range of 6 to 8% by weight and opadry enteric pink in the range of 10 to 14% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
163. The formulation as claimed in claim 15, wherein rabeprazole sodium enteric-coated pellets in the range of 6 to 20% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
164. The formulation as claimed in claim 157, wherein (S)-rabeprazole sodium in the range of 3 to 23% by weight, light magnesium oxide in the range of
0.5 to 2.5% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 25 to 78% by weight, mannitol in the range of 9 to 80% by weight, polyvinylpyrrolidone s-630 in the range of 0.5 to 4% by weight, starch in the range of 0.5 to 2.5% by weight, hydroxypropylcellulose
(low-substituted) or hydroxypropylcellulose in the range of 0.5 to 23% by weight, sodium stearyl fumarate in the range of 0.5 to 2.5% by weight, hydroxypropylmethylcellulose-15cps in the range of 2.5 to 15% by weight, acryl EZE in the range of 7 to 28% by weight, opadry organic white in the range of 3 to 10% by weight and opadry enteric pink in the range of 7 to
17% by weight, based on the total weight of pharmaceutical dosage form.
165. The formulation as claimed in claim 164, wherein (S)-rabeprazole sodium in the range of 6 to 14% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 43 to 60% by weight; mannitol in the range of 16 to 21 % by weight, polyvinylpyrrolidone s-630 in the range of 1.5 to 2.5% by weight, starch in the range of 1 to 2% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose in the range of 13 to 17% by weight, sodium stearyl fumarate in the range of 1 to 2% by weight, hydroxypropylmethylcellulose-iδcps in the range of 4.5 to
5.5% by weight and acryl EZE in the range of 13 to 17 % by weight, based on the total weight of enteric coated tablets
166. The formulation as claimed in claim 165, wherein (S)-rabeprazole sodium is 7.69% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 53.8% by weight; mannitol is 18.5% by weight, polyvinylpyrrolidone s-630 is 1.92% by weight, starch is 1.15% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose is 15.4% by weight, sodium stearyl fumarate is 1.54% by weight, hydroxypropyl
methylcellulose-15cps is 5% by weight and acryl EZE is 14.7% by weight, based on the total weight of enteric coated tablets.
167. The formulation as claimed in claim 165, wherein (S)-rabeprazole sodium is 12.5% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 48.8% by weight; mannitol is 18.8% by weight, polyvinylpyrrolidone s-630 is 2.19% by weight, starch is 1.25% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose is 15% by weight, sodium stearyl fumarate is 1.56% by weight, hydroxypropylmethylcellulose-iδcps is 5% by weight and acryl EZE is
14.7% by weight, based on the total weight of enteric coated tablets.
168. The formulation as claimed in claim 164, wherein (S)-rabeprazole sodium in the range of 6 to 9% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 46 to 58% by weight, light magnesium oxide in the range of 1 to 2% by weight; mannitol in the range of 16 to 77% by weight, polyvinylpyrrolidone s-630 in the range of 1.5 to 2.5% by weight, starch in the range of 1 to 1.5% by weight, hydroxypropylmethylcellulose-15cps in the range of 6 to 8% by weight, acryl EZE in the range of 10 to 14% by weight, opadry organic white in the range of 6 to 8% by weight and opadry enteric pink in the range of 10 to 14% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
169. The formulation as claimed in claim 15, wherein (S)-rabeprazole sodium enteric-coated pellets in the range of 6 to 20% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
170. The formulation as claimed in claim 5, wherein the antiulcerative substituted benzimidazole is pantoprazole, (S)-pantoprazole or a salt thereof; stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate; mannitol, starch, polyvinylpyrrolidone-630 or polyvinyl pyrrolidone k-30; hydroxypropylcellulose or hydroxypropylcellulose (low- substituted); sodium stearyl fumarate, hydroxypropylmethylcellulose-15cps, acryl EZE, light calcium carbonate, crospovidone, propylene glycol,
croscarmellose sodium, sodium lauryl sulfate, hydroxypropylmethylcellulose E5 and opadry enteric pink.
171. The formulation as claimed in claim 170, wherein pantoprazole or a salt thereof in the range of 7 to 40% by weight equivalent to pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 19 to 62% by weight, light calcium carbonate in the range of 4 to 11% by weight; mannitol in the range of 7 to 70% by weight, croscarmellose sodium in the range of 1.5 to 5% by weight, crospovidone in the range of 1.5 to 5% by weight, sodium lauryl sulfate in the range of 0.25 to 1.25% by weight, polyvinylpyrrolidone s-630 or polyvinylpyrrolidone k-30 in the range of 0.5 to 4% by weight; starch in the range of 0.5 to 2.5% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose in the range of 7 to 24% by weight; hydroxypropylmethylcellulose E5 in the range of 4 to 12% by weight, sodium stearyl fumarate in the range of 0.5 to 2.5% by weight, propylene glycol in the range of 0.1 to 1.5% by weight, hydroxypropylmethylcellulose-15cps in the range of 2.5 to 15% by weight, acryl EZE in the range of 8 to 21% by weight and opadry enteric pink in the range of 9 to 21% by weight, based on the total weight of pharmaceutical dosage form.
172. The formulation as claimed in claim 171 , wherein pantoprazole or a salt thereof in the range of 15 to 32% by weight equivalent to pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 29 to 49% by weight; mannitol in the range of 16 to 21% by weight, polyvinylpyrrolidone s-630 in the range of 1 to 2.5% by weight, starch in the range of 1 to 2% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose in the range of 13 to 17% by weight; sodium stearyl fumarate in the range of 1 to 2% by weight, hydroxypropylmethylcellulose- 5cps in the range of 3 to 7% by weight and acryl EZE in the range of 12 to
16% by weight, based on the total weight of enteric coated tablets.
173. The formulation as claimed in claim 172, wherein pantoprazole or a salt thereof is 17.4% by weight equivalent to pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy
magnesium oxide and heavy sodium carbonate is 44.2% by weight; mannitol is 18.5% by weight, polyvinylpyrrolidone s-630 is 1.92% by weight, starch is 1.15% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose is 15.4% by weight; sodium stearyl fumarate is 1.54% by weight, propylene glycol in the range of 0.5 to 1% by weight, hydroxypropylmethylcellulose-15cps is 5% by weight and acryl EZE is 14% by weight, based on the total weight of enteric coated tablets.
174. The formulation as claimed in claim 172, wherein pantoprazole or a salt thereof is 28.3% by weight equivalent to pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 33% by weight; mannitol is 18.8% by weight, polyvinylpyrrolidone s-630 is 2.19% by weight, starch is 1.25% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose is 15% by weight; sodium stearyl fumarate is 1.56% by weight, hydroxypropylmethylcellulose-iδcps is 5% by weight and acryl
EZE is 14% by weight, based on the total weight of enteric coated tablets.
175. The formulation as claimed in claim 171, wherein pantoprazole or a salt thereof in the range of 11 to 15% by weight equivalent to pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide, and heavy sodium carbonate in the range of 33 to 41% by weight, light calcium carbonate in the range of 6.5 to 8.5% by weight; mannitol in the range of 11 to 52% by weight, polyvinylpyrrolidone s-630 in the range of 1 to 2% by weight or polyvinylpyrrolidone k-30 in the range of 1.5 to 2.5% by weight, starch in the range of 0.5 to 2.5% by weight, croscarmellose sodium in the range of
2.5 to 3.5% by weight, crospovidone in the range of 2.5 to 3.5% by weight, sodium lauryl sulfate in the range of 0.2 to 1% by weight, hydroxypropylmethylcellulose E5 in the range of 7 to 9% by weight, propylene glycol in the range of 0.5 to 1% by weight, hydroxypropylmethylcellulose-15cps in the range of 9 to 11 % by weight, acryl EZE in the range of 13.5 to 16.5% by weight and opadry enteric pink in the range of 13.5 to 16.5% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
176. The formulation as claimed in claim 15, wherein pantoprazole enteric- coated pellets are in the range of 10 to 22% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
177. The formulation as claimed in claim 170, wherein (S)-pantoprazole or a salt thereof in the range of 7 to 40% by weight equivalent to (S)- pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 19 to 62% by weight, light calcium carbonate in the range of 4 to 1 1% by weight; mannitol in the range of 7 to 70% by weight, croscarmellose sodium in the range of 1.5 to 5% by weight, crospovidone in the range of 1.5 to 5% by weight, sodium lauryl sulfate in the range of 0.25 to 1.25% by weight, polyvinylpyrrolidone s-630 or polyvinylpyrrolidone k-30 in the range of 0.5 to 4% by weight; starch in the range of 0.5 to 2.5% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose in the range of 7 to 24% by weight; hydroxypropylmethylcellulose E5 in the range of 4 to 12% by weight, sodium stearyf fumarate in the range of 0.5 to 2.5% by weight, propylene glycol in the range of 0.1 to 1.5% by weight, hydroxypropylmethylcellulose- 15cps in the range of 2.5 to 15% by weight, acryl EZE in the range of 8 to 21% by weight and opadry enteric pink in the range of 9 to 21% by weight, based on the total weight of pharmaceutical dosage form.
178. The formulation as claimed in claim 177, wherein (S)-pantoprazole or a salt thereof in the range of 15 to 32% by weight equivalent to (S)- pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 29 to 49% by weight; mannitol in the range of 16 to 21% by weight, polyvinylpyrrolidone s-630 in the range of 1 to 2.5% by weight, starch in the range of 1 to 2% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose in the range of 13 to 17% by weight; sodium stearyl fumarate in the range of 1 to 2% by weight, hydroxypropylmethylcellulose-5cps in the range of 3 to 7% by weight and acryl EZE in the range of 12 to 16% by weight, based on the total weight of enteric coated tablets.
179. The formulation as claimed in claim 178, wherein (S)-pantoprazole or a salt thereof is 17.4% by weight equivalent to (S)-pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 44.2% by weight; mannitol is 18.5% by weight, polyvinylpyrrolidone s-630 is 1.92% by weight, starch is 1.15% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose is 15.4% by weight; sodium stearyl fumarate is 1.54% by weight, propylene glycol in the range of 0.5 to 1 % by weight, hydroxypropylmethylcellulose-15cps is 5% by weight and acryl EZE is 14% by weight, based on the total weight of enteric coated tablets.
180. The formulation as claimed in claim 178, wherein (S)-pantoprazole or a salt thereof is 28.3% by weight equivalent to (S)-pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 33% by weight; mannitol is 18.8% by weight, polyvinylpyrrolidone s-630 is 2.19% by weight, starch is 1.25% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose is 15% by weight; sodium stearyl fumarate is 1.56% by weight, hydroxypropylmethylcellulose-15cps is 5% by weight and acryl EZE is 14% by weight, based on the total weight of enteric coated tablets.
181. The formulation as claimed in claim 177, wherein (S)-pantoprazole or a salt thereof in the range of 11 to 15% by weight equivalent to (S)- pantoprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide, and heavy sodium carbonate in the range of 33 to 41 % by weight, light calcium carbonate in the range of 6.5 to 8.5% by weight; mannitol in the range of 11 to 52% by weight, polyvinylpyrrolidone s-630 in the range of 1 to 2% by weight or polyvinylpyrrolidone k-30 in the range of 1.5 to 2.5% by weight, starch in the range of 0.5 to 2.5% by weight, croscarmellose sodium in the range of 2.5 to 3.5% by weight, crospovidone in the range of 2.5 to 3.5% by weight, sodium lauryl sulfate in the range of 0.2 to 1 % by weight, hydroxypropylmethylcellulose E5 in the range of 7 to 9% by weight, propylene glycol in the range of 0.5 to 1% by weight, hydroxypropylmethylcellulose-15cps in the range of 9 to 11 % by weight, acryl EZE in the range of 13.5 to 16.5% by weight and opadry enteric pink
in the range of 13.5 to 16.5% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
182. The formulation as claimed in claim 15, wherein (S)-pantoprazole enteric- coated pellets are in the range of 10 to 22% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
183. The formulation as claimed in claim 5, wherein the formulation comprises omeprazole or a salt thereof, disodium hydrogen phosphate, calcium carbonate, lactose, sucrose, methacrylic acid L-30D, tween 80, mannitol, polyvinylpyrrolidone k-30 hydroxypropylmethylcellulose E5, propylene glycol, sodium hydroxide, diethyl phthalate, titanium dioxide, cetyl alcohol and purified talc.
184. The formulation as claimed in claim 183, wherein omeprazole or a salt thereof in the range of 5 to 15% by weight, disodium hydrogen phosphate in the range of 0.5 to 2% by weight, light calcium carbonate in the range of 2 to 5% by weight, lactose in the range of 2 to 5% by weight, sucrose in the range of 16 to 39% by weight, mannitol in the range of 10 to 24% by weight, polyvinylpyrrolidone k-30 in the range of 0.1 to 0.5% by weight, hydroxypropylmethylcellulose E5 in the range of 5 to 13% by weight, propylene glycol in the range of 0.5 to 2% by weight, sodium hydroxide in the range of 0.05 to 0.1 % by weight, tween 80 in the range of 0.1 to 0.5% by weight, diethyl phthalate in the range of 1.5 to 3.5% by weight, titanium dioxide in the range of 0.01 to 0.1 % by weight, methacrylic acid L-30D in the range of 15 to 35% by weight, cetyl alcohol in the range of 0.1 to 1.5% by weight and purified talc in the range of 0.002 to 0.02% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
185. The formulation as claimed in claim 184, wherein omeprazole or a salt thereof in the range of 7 to 10% by weight, disodium hydrogen phosphate in the range of 1 to 1.5% by weight, light calcium carbonate in the range of 3 to 4% by weight, lactose in the range of 3 to 4% by weight, sucrose in the range of 25 to 31 % by weight, mannitol in the range of 15 to 19% by weight, polyvinylpyrrolidone k-30 in the range of 0.1 to 0.3% by weight, hydroxy propylmethylcellulose E5 in the range of 7 to 10% by weight, propylene glycol in the range of 0.5 to 1% by weight, sodium, hydroxide in the range of 0.05 to 0.5% by weight, tween 80 in the range of 0.2 to 0.3% by weight,
diethyl phthalate in the range of 2 to 3% by weight, titanium dioxide in the range of 0.02 to 0.06% by weight, methacrylic acid L-30D in the range of 23 to 28% by weight, cetyl alcohol in the range of 0.5 to 1 % by weight and purified talc in the range of 0.003 to 0.01 % by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
186. The formulation as claimed in claim 15, wherein omeprazole enteric- coated pellets are in the range of 5 to 15% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
187. The formulation as claimed in claim 5, wherein the antiulcerative benzimidazole sulfoxide is esomeprazole or a salt thereof; stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate; mannitol, starch, crospovidone, polyvinylpyrolidone s-630; or polyvinylpyrrolidone k-30, hydroxypropylcellulose or hydroxypropylcellulose (low-substituted); acryl EZE, croscarmellose sodium, light calcium carbonate, sodium stearyl fumarate, hydroxypropylmethy!cellulose-15cps, sodium lauryl sulfate, propylene glycol, hydroxypropylmethylcellulose E5 and opadry enteric pink.
188. The formulation as claimed in claim 187, wherein esomeprazole or a salt thereof in the range of 7 to 40% by weight equivalent to esomeprazole, croscarmellose sodium in the range of 1.5 to 4.5% by weight, crospovidone in the range of 1.5 to 4.5% by weight, sodium lauryl sulfate in the range of 0.1 to 1.0% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 20 to 63% by weight, light calcium carbonate in the range of 4 to 11 % by weight; polyvinylpyrrolidone k-30 or polyvinylpyrrolidone s-630 in the range of 0.5 to 4% by weight; hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose in the range of 7 to 24% by weight; mannitol in the range of 9 to 67% by weight, hydroxypropylmethylcellulose E5 in the range of 4.5 to 11.5% by weight, starch in the range of 0.5 to 2.5% by weight, propylene glycol in the range of 0.25 to 1.5% by weight, sodium stearyl fumarate in the range of 0.5 to 2.5% by weight, hydroxypropylmethylcellulose-15cps in the range of 2.5 to 15% by weight, acryl EZE in the range of 7 to 25% by weight and opadry
enteric pink in the range. of 9 to 21% by weight, based on the total weight of pharmaceutical dosage form.
189. The formulation as claimed in claim 188, wherein esomeprazole or a salt thereof in the range of 15 to 31% by weight equivalent to esomeprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 30 to 49% by weight; hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose in the range of 14 to 17% by weight; mannitol in the range of 17 to 21% by weight, polyvinylpyrrolidone s-630 in the range of 1.5 to 2.5% by weight, starch in the range of 1 to 1.5% by weight, sodium stearyl fumarate in the range of 1 to 2% by weight, hydroxypropylmethylcellulose-15cps in the range of 4.5 to 5.5% by weight and acryl EZE in the range of 13 to 16% by weight, based on the total weight of enteric-coated tablets.
190. The formulation as claimed in claim 189, wherein esomeprazole or a salt thereof is 17.2% by weight equivalent to esomeprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 44.4% by weight; mannitol is 18.5% by weight, polyvinylpyrrolidone s-630 is 1.92% by weight, sodium stearyl fumarate is 1.54% by weight, starch is 1.15% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose is 15.4% by weight; hydroxypropylmethylcellulose-15cps is 5% by weight and acryl EZE is 14% by weight, based on the total weight of enteric coated tablets.
191. The formulation as claimed in claim 189, wherein esomeprazole or a salt thereof is 27.9% by weight equivalent to esomeprazole, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate is 33.4% by weight; mannitol is 18.8% by weight, polyvinylpyrrolidone s-630 is 2.19% by weight, starch is 1.25% by weight, hydroxypropylcellulose (low-substituted) or hydroxypropylcellulose is 15% by weight; sodium stearyl fumarate is 1.56% by weight, hydroxypropylmethylcellulose-15cps is 5% by weight and acryl EZE is 14% by weight, based on the total weight of enteric coated tablets.
192. The formulation as claimed in claim 188, wherein esomeprazole or a salt thereof in the range of 12 to 15% by weight equivalent to esomeprazole,
light calcium carbonate in the range of 6.5 to 8.5% by weight, croscarmellose sodium in the range of 2.5 to 3% by weight, crospovidone in the range of 2.5 to 3% by weight, sodium lauryl sulfate in the range of 0.3 to 0.8% by weight, stabilizers selected from heavy calcium carbonate, heavy magnesium carbonate, heavy magnesium oxide and heavy sodium carbonate in the range of 33 to 41% by weight; mannitol in the range of 20 to 52% by weight, polyvinylpyrrolidone s-630 or polyvinylpyrrolidone k-30 in the range of 1 to 2.5% by weight; starch in the range of 0.5 to 1.5% by weight, hydroxypropylmethylcellulose E5 in the range of 7 to 9% by weight, hydroxypropylmethylcellulose-iδcps in the range of 9 to 11% by weight, propylene glycol in the range of 0.5 to 1% by weight, acryl EZE in the range of 14 to 17% by weight and opadry enteric pink in the range of 14 to 17% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
193. The formulation as claimed in claim 15, wherein esomeprazole enteric- coated pellets are in the range of 10 to 20% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
194. The formulation as claimed in claim 5, wherein the formulations comprises lansoprazole or (S)- lansoprazole; calcium carboxymethylcellulose, light magnesium carbonate, lactose, sucrose, methacrylic acid L-30D, mannitol, polyvinylpyrrolidone k-30 hydroxypropylmethylcellulose E5, starch, propylene glycol, sodium hydroxide tween 80, diethyl phthalate, titanium dioxide and cetyl alcohol.
195. The formulation as claimed in claim 194, wherein lansoprazole in the range of 5 to 12% by weight, light magnesium carbonate in the range of 3 to 10% by weight, lactose in the range of 3 to 10% by weight, sucrose in the range of 10 to 24% by weight, calcium carboxymethylcellulose in the range of 2 to 7% by weight, mannitol in the range of 5 to 14% by weight, tween 80 in the range of 0.1 to 0.5% by weight, polyvinylpyrrolidone k-30 in the range of 0.1 to 0.5% by weight, starch in the range of 4 to 11 %by weight, methacrylic acid L-30D in the range of 14.5 to 35% by weight, hydroxypropylmethylcellulose E5 in the range of 5 to 13% by weight, propylene glycol in the range of 0.2 to 1.5% by weight, sodium hydroxide in the range of 0.05 to 0.25% by weight, diethyl phthalate in the range of 1 to
3.5% by weight, titanium dioxide in the range of 0.5 to 2% by weight and cetyl alcohol in the range of 0.1 to 1.5% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
196. The formulation as claimed in claim 195, wherein lansoprazole in the range of 7 to 10% by weight, light magnesium carbonate in the range of 5.5 to 7.5% by weight, lactose in the range of 5.5 to 7.5 % by weight, sucrose in the range of 15 to 19% by weight, calcium carboxymethylcellulose in the range of 4 to 6 % by weight, mannitol in the range of 8 to 1 1 % by weight, tween 80 in the range of 0.1 to 0.4% by weight, polyvinylpyrrolidone k-30 in the range of 0.1 to 0.3% by weight, starch in the range of 6 to 8% by weight, methacrylic acid L-30D in the range of 22 to 28% by weight, hydroxypropylmethylcellulose E5 in the range of 7.5 to 10% by weight, propylene glycol in the range of 0.5 to 1% by weight, sodium hydroxide in the range of 0.1 to 0.2% by weight, diethyl phthalate in the range of 2 to 3% by weight, titanium dioxide in the range of 0.5 to 1.5% by weight and cetyl alcohol in the range of 0.5 to 1% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
197. The formulation as claimed in claim 15, wherein lansoprazole enteric- coated pellets are in the range of 5 to 15% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
198. The formulation as claimed in claim 194, wherein (S)-lansoprazole in the range of 5 to 12% by weight, light magnesium carbonate in the range of 3 to 10% by weight, lactose in the range of 3 to 10% by weight, sucrose in the range of 10 to 24% by weight, calcium carboxymethylcellulose in the range of 2 to 7% by weight, mannitol in the range of 5 to 14% by weight, tween 80 in the range of 0.1 to 0.5% by weight, polyvinylpyrrolidone k-30 in the range of 0.1 to 0.5% by weight, starch in the range of 4 to 11%by weight, methacrylic acid L-30D in the range of 14.5 to 35% by weight, hydroxypropylmethylcellulose E5 in the range of 5 to 13% by weight, propylene glycol in the range of 0.2 to 1 ,5% by weight, sodium hydroxide in the range of 0.05 to 0.25% by weight, diethyl phthalate in the range of 1 to 3.5% by weight, titanium dioxide in the range of 0.5 to 2% by weight and cetyl alcohol in the range of 0.1 to 1.5% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
199. The formulation as claimed in claim 198, wherein (S)-lansoprazole in the range of 7 to 10% by weight, light magnesium carbonate in the range of 5.5 to 7.5% by weight, lactose in the range of 5.5 to 7.5 % by weight, sucrose in the range of 15 to 19% by weight, calcium carboxymethylcellulose in the range of 4 to 6 % by weight, mannitol in the range of 8 to 11% by weight, tween 80 in the range of 0.1 to 0.4% by weight, polyvinylpyrrolidone k-30 in the range of 0.1 to 0.3% by weight, starch in the range of 6 to 8% by weight, methacrylic acid L-30D in the range of 22 to 28% by weight, hydroxypropylmethylcellulose E5 in the range of 7.5 to 10% by weight, propylene glycol in the range of 0.5 to 1% by weight, sodium hydroxide in the range of 0.1 to 0.2% by weight, diethyl phthalate in the range of 2 to 3% by weight, titanium dioxide in the range of 0.5 to 1.5% by weight and cetyl alcohol in the range of 0.5 to 1% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
200. The formulation as claimed in claim 15, wherein lansoprazole enteric- coated pellets are in the range of 5 to 15% by weight, based on the total weight of pellets that are filled in hard gelatin capsules.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/IN2005/000203 WO2006134611A1 (en) | 2005-06-16 | 2005-06-16 | Compositions of antiulcerative substituted benzimidazoles |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/IN2005/000203 WO2006134611A1 (en) | 2005-06-16 | 2005-06-16 | Compositions of antiulcerative substituted benzimidazoles |
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| WO2006134611A1 true WO2006134611A1 (en) | 2006-12-21 |
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| CN101756945B (en) * | 2008-12-24 | 2012-06-27 | 鲁南制药集团股份有限公司 | Citrate mosapride pill |
| WO2013081566A1 (en) * | 2011-11-25 | 2013-06-06 | Mahmut Bilgic | A formulation comprising benzimidazole |
| CN103599087A (en) * | 2013-05-21 | 2014-02-26 | 海南海力制药有限公司 | Rabeprazole sodium enteric-coated pellet and preparation method thereof |
| WO2016155786A1 (en) * | 2015-03-31 | 2016-10-06 | Laboratorios Bagó S.A. | Enteric-coated pellets containing a proton pump inhibitor |
| US20160331688A1 (en) * | 2014-01-31 | 2016-11-17 | Shionogi & Co., Ltd. | Sustained release formulation |
| WO2017185123A1 (en) * | 2016-04-29 | 2017-11-02 | Alan Thompson | Veterinary composition |
| EP3354262A1 (en) * | 2017-01-31 | 2018-08-01 | Sanovel Ilac Sanayi ve Ticaret A.S. | Enteric coated pharmaceutical compositions of dexlansoprazole |
| CN109125282A (en) * | 2018-09-05 | 2019-01-04 | 珠海润都制药股份有限公司 | A kind of omeprazole enteric-coated capsules and preparation method thereof |
| JP2021107333A (en) * | 2019-12-27 | 2021-07-29 | 小林製薬株式会社 | Oral pharmaceutical composition |
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| US20040092511A1 (en) * | 1999-12-10 | 2004-05-13 | Billstein Stephan Anthony | Pharmaceutical combinations and their use in treating gastrointestinal and abdominal viscera disorders |
| WO2005051384A1 (en) * | 2003-11-25 | 2005-06-09 | Pfizer Limited | Stabilised pharmaceutical compositions |
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| US20040092511A1 (en) * | 1999-12-10 | 2004-05-13 | Billstein Stephan Anthony | Pharmaceutical combinations and their use in treating gastrointestinal and abdominal viscera disorders |
| WO2005051384A1 (en) * | 2003-11-25 | 2005-06-09 | Pfizer Limited | Stabilised pharmaceutical compositions |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101756945B (en) * | 2008-12-24 | 2012-06-27 | 鲁南制药集团股份有限公司 | Citrate mosapride pill |
| WO2013081566A1 (en) * | 2011-11-25 | 2013-06-06 | Mahmut Bilgic | A formulation comprising benzimidazole |
| CN103599087A (en) * | 2013-05-21 | 2014-02-26 | 海南海力制药有限公司 | Rabeprazole sodium enteric-coated pellet and preparation method thereof |
| US20160331688A1 (en) * | 2014-01-31 | 2016-11-17 | Shionogi & Co., Ltd. | Sustained release formulation |
| WO2016155786A1 (en) * | 2015-03-31 | 2016-10-06 | Laboratorios Bagó S.A. | Enteric-coated pellets containing a proton pump inhibitor |
| RU2679652C1 (en) * | 2015-03-31 | 2019-02-12 | Лабораториос Баго С. А. | Method of obtaining enteric coated granules containing proton pump inhibitor, and pharmaceutical compositions, containing multiple particles and such granules |
| US10786458B2 (en) | 2015-03-31 | 2020-09-29 | Laboratorios Bago S.A. | Procedure for preparing enteric-coated pellets containing a proton pump inhibitor and multi-particle pharmaceutical compositions containing them |
| WO2017185123A1 (en) * | 2016-04-29 | 2017-11-02 | Alan Thompson | Veterinary composition |
| EP3354262A1 (en) * | 2017-01-31 | 2018-08-01 | Sanovel Ilac Sanayi ve Ticaret A.S. | Enteric coated pharmaceutical compositions of dexlansoprazole |
| CN109125282A (en) * | 2018-09-05 | 2019-01-04 | 珠海润都制药股份有限公司 | A kind of omeprazole enteric-coated capsules and preparation method thereof |
| CN109125282B (en) * | 2018-09-05 | 2020-07-14 | 珠海润都制药股份有限公司 | Omeprazole enteric capsule and preparation method thereof |
| JP2021107333A (en) * | 2019-12-27 | 2021-07-29 | 小林製薬株式会社 | Oral pharmaceutical composition |
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