GB2625579A - An orally disintegrating tablet containing gabapentin or pharmaceutically acceptable salts thereof and the process of preparing the same - Google Patents
An orally disintegrating tablet containing gabapentin or pharmaceutically acceptable salts thereof and the process of preparing the same Download PDFInfo
- Publication number
- GB2625579A GB2625579A GB2219356.9A GB202219356A GB2625579A GB 2625579 A GB2625579 A GB 2625579A GB 202219356 A GB202219356 A GB 202219356A GB 2625579 A GB2625579 A GB 2625579A
- Authority
- GB
- United Kingdom
- Prior art keywords
- orally disintegrating
- range
- disintegrating tablet
- tablet according
- gabapentin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 title claims abstract description 148
- 229960002870 gabapentin Drugs 0.000 title claims abstract description 74
- 239000006191 orally-disintegrating tablet Substances 0.000 title claims abstract description 60
- 238000000034 method Methods 0.000 title claims description 19
- 150000003839 salts Chemical class 0.000 title claims description 14
- 230000008569 process Effects 0.000 title description 5
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 60
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 42
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 42
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 42
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 42
- 229920002261 Corn starch Polymers 0.000 claims abstract description 37
- 235000019759 Maize starch Nutrition 0.000 claims abstract description 37
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical group C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims abstract description 35
- 239000003826 tablet Substances 0.000 claims abstract description 35
- 229960000913 crospovidone Drugs 0.000 claims abstract description 33
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims abstract description 33
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims abstract description 33
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 claims abstract description 32
- 235000010358 acesulfame potassium Nutrition 0.000 claims abstract description 32
- 229960004998 acesulfame potassium Drugs 0.000 claims abstract description 32
- 239000000619 acesulfame-K Substances 0.000 claims abstract description 32
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 30
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims abstract description 27
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims abstract description 27
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims abstract description 27
- 229940071676 hydroxypropylcellulose Drugs 0.000 claims abstract description 27
- 239000003085 diluting agent Substances 0.000 claims abstract description 18
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical group C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229920001992 poloxamer 407 Polymers 0.000 claims abstract description 14
- 229940044476 poloxamer 407 Drugs 0.000 claims abstract description 14
- 239000011230 binding agent Substances 0.000 claims abstract description 12
- 239000007884 disintegrant Substances 0.000 claims abstract description 12
- 239000003381 stabilizer Substances 0.000 claims abstract description 12
- 239000000314 lubricant Substances 0.000 claims abstract description 11
- 235000003599 food sweetener Nutrition 0.000 claims abstract description 9
- 239000003765 sweetening agent Substances 0.000 claims abstract description 9
- 239000002245 particle Substances 0.000 claims abstract description 7
- 238000002156 mixing Methods 0.000 claims abstract description 6
- 206010036376 Postherpetic Neuralgia Diseases 0.000 claims abstract description 5
- 208000004296 neuralgia Diseases 0.000 claims abstract description 5
- 208000021722 neuropathic pain Diseases 0.000 claims abstract description 5
- 230000002093 peripheral effect Effects 0.000 claims abstract description 5
- 229940057948 magnesium stearate Drugs 0.000 claims abstract 3
- 230000002265 prevention Effects 0.000 claims abstract 2
- 238000007873 sieving Methods 0.000 claims abstract 2
- 239000000203 mixture Substances 0.000 claims description 37
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 18
- 239000000377 silicon dioxide Substances 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 229920001903 high density polyethylene Polymers 0.000 claims description 6
- 239000004700 high-density polyethylene Substances 0.000 claims description 6
- 239000005022 packaging material Substances 0.000 claims description 6
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 5
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 5
- 235000010443 alginic acid Nutrition 0.000 claims description 5
- 229920000615 alginic acid Polymers 0.000 claims description 5
- 239000000783 alginic acid Substances 0.000 claims description 5
- 229960001126 alginic acid Drugs 0.000 claims description 5
- 150000004781 alginic acids Chemical class 0.000 claims description 5
- 235000010980 cellulose Nutrition 0.000 claims description 5
- 229920002678 cellulose Polymers 0.000 claims description 5
- 239000001913 cellulose Substances 0.000 claims description 5
- -1 dextrates Substances 0.000 claims description 5
- 238000007907 direct compression Methods 0.000 claims description 5
- 239000000600 sorbitol Substances 0.000 claims description 5
- 206010010904 Convulsion Diseases 0.000 claims description 4
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 4
- 108010010803 Gelatin Proteins 0.000 claims description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 4
- 229920002907 Guar gum Polymers 0.000 claims description 4
- 229920000881 Modified starch Polymers 0.000 claims description 4
- 229940123973 Oxygen scavenger Drugs 0.000 claims description 4
- DLRVVLDZNNYCBX-UHFFFAOYSA-N Polydextrose Polymers OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(O)O1 DLRVVLDZNNYCBX-UHFFFAOYSA-N 0.000 claims description 4
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 4
- 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 4
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 4
- 229920000159 gelatin Polymers 0.000 claims description 4
- 239000008273 gelatin Substances 0.000 claims description 4
- 229940014259 gelatin Drugs 0.000 claims description 4
- 235000019322 gelatine Nutrition 0.000 claims description 4
- 235000011852 gelatine desserts Nutrition 0.000 claims description 4
- 235000010417 guar gum Nutrition 0.000 claims description 4
- 239000000665 guar gum Substances 0.000 claims description 4
- 229960002154 guar gum Drugs 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 4
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 4
- 229920002472 Starch Polymers 0.000 claims description 3
- 229960001031 glucose Drugs 0.000 claims description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 3
- 229920001983 poloxamer Polymers 0.000 claims description 3
- 210000003296 saliva Anatomy 0.000 claims description 3
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 3
- 235000010234 sodium benzoate Nutrition 0.000 claims description 3
- 239000004299 sodium benzoate Substances 0.000 claims description 3
- 235000019698 starch Nutrition 0.000 claims description 3
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 claims description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 108010011485 Aspartame Proteins 0.000 claims description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 2
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 2
- 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 description 2
- 235000019739 Dicalciumphosphate Nutrition 0.000 claims description 2
- 239000001856 Ethyl cellulose Substances 0.000 claims description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 2
- 239000001329 FEMA 3811 Substances 0.000 claims description 2
- 229930091371 Fructose Natural products 0.000 claims description 2
- 239000005715 Fructose Substances 0.000 claims description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 2
- 235000010469 Glycine max Nutrition 0.000 claims description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 2
- 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 2
- 229920000161 Locust bean gum Polymers 0.000 claims description 2
- 239000005913 Maltodextrin Substances 0.000 claims description 2
- 229920002774 Maltodextrin Polymers 0.000 claims description 2
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- ILRKKHJEINIICQ-OOFFSTKBSA-N Monoammonium glycyrrhizinate Chemical compound N.O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C(O)=O)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O ILRKKHJEINIICQ-OOFFSTKBSA-N 0.000 claims description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 2
- 229920001100 Polydextrose Polymers 0.000 claims description 2
- 239000004743 Polypropylene Substances 0.000 claims description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 2
- 229920003081 Povidone K 30 Polymers 0.000 claims description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 2
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 claims description 2
- 229920002125 Sokalan® Polymers 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- 239000004376 Sucralose Substances 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- 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 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
- 150000001413 amino acids Chemical class 0.000 claims description 2
- 239000000605 aspartame Substances 0.000 claims description 2
- 235000010357 aspartame Nutrition 0.000 claims description 2
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 2
- 229960003438 aspartame Drugs 0.000 claims description 2
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose 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-QUYVBRFLSA-N 0.000 claims description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 2
- 239000004327 boric acid Substances 0.000 claims description 2
- 239000001506 calcium phosphate Substances 0.000 claims description 2
- 239000000378 calcium silicate Substances 0.000 claims description 2
- 229910052918 calcium silicate Inorganic materials 0.000 claims description 2
- 235000012241 calcium silicate Nutrition 0.000 claims description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 2
- 235000013539 calcium stearate Nutrition 0.000 claims description 2
- 239000008116 calcium stearate Substances 0.000 claims description 2
- 229940078456 calcium stearate Drugs 0.000 claims description 2
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 claims description 2
- 229960001631 carbomer Drugs 0.000 claims description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 2
- 235000010418 carrageenan Nutrition 0.000 claims description 2
- 239000000679 carrageenan Substances 0.000 claims description 2
- 229920001525 carrageenan Polymers 0.000 claims description 2
- 229940113118 carrageenan Drugs 0.000 claims description 2
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 2
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 2
- 229940109275 cyclamate Drugs 0.000 claims description 2
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical group OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 claims description 2
- 229940096516 dextrates Drugs 0.000 claims description 2
- 239000008121 dextrose Substances 0.000 claims description 2
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 claims description 2
- 229940038472 dicalcium phosphate Drugs 0.000 claims description 2
- 229910000390 dicalcium phosphate Inorganic materials 0.000 claims description 2
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims description 2
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 2
- 229920001249 ethyl cellulose Polymers 0.000 claims description 2
- 229960004667 ethyl cellulose Drugs 0.000 claims description 2
- 239000008103 glucose Substances 0.000 claims description 2
- 235000001727 glucose Nutrition 0.000 claims description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 2
- 229940071826 hydroxyethyl cellulose Drugs 0.000 claims description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
- 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 2
- 239000008101 lactose Substances 0.000 claims description 2
- 229960001375 lactose Drugs 0.000 claims description 2
- 235000010420 locust bean gum Nutrition 0.000 claims description 2
- 239000000711 locust bean gum Substances 0.000 claims description 2
- 229940035034 maltodextrin Drugs 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 235000010981 methylcellulose Nutrition 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- 235000019426 modified starch Nutrition 0.000 claims description 2
- ITVGXXMINPYUHD-CUVHLRMHSA-N neohesperidin dihydrochalcone Chemical compound C1=C(O)C(OC)=CC=C1CCC(=O)C(C(=C1)O)=C(O)C=C1O[C@H]1[C@H](O[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 ITVGXXMINPYUHD-CUVHLRMHSA-N 0.000 claims description 2
- 229940089953 neohesperidin dihydrochalcone Drugs 0.000 claims description 2
- 235000010434 neohesperidine DC Nutrition 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- 229920001277 pectin Polymers 0.000 claims description 2
- 235000010987 pectin Nutrition 0.000 claims description 2
- 239000001814 pectin Substances 0.000 claims description 2
- 235000013856 polydextrose Nutrition 0.000 claims description 2
- 239000001259 polydextrose Substances 0.000 claims description 2
- 229940035035 polydextrose Drugs 0.000 claims description 2
- 229920001155 polypropylene Polymers 0.000 claims description 2
- 229920001282 polysaccharide Polymers 0.000 claims description 2
- 239000005017 polysaccharide Substances 0.000 claims description 2
- 150000004804 polysaccharides Chemical class 0.000 claims description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 2
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 2
- 229940069328 povidone Drugs 0.000 claims description 2
- 235000019204 saccharin Nutrition 0.000 claims description 2
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 claims description 2
- 229940081974 saccharin Drugs 0.000 claims description 2
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 claims description 2
- 229940085605 saccharin sodium Drugs 0.000 claims description 2
- 239000001632 sodium acetate Substances 0.000 claims description 2
- 235000017281 sodium acetate Nutrition 0.000 claims description 2
- 235000010413 sodium alginate Nutrition 0.000 claims description 2
- 239000000661 sodium alginate Substances 0.000 claims description 2
- 229940005550 sodium alginate Drugs 0.000 claims description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 2
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 claims description 2
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims description 2
- 239000008107 starch Substances 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- 235000019408 sucralose Nutrition 0.000 claims description 2
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 claims description 2
- 239000005720 sucrose Substances 0.000 claims description 2
- 239000001993 wax Substances 0.000 claims description 2
- 239000000811 xylitol Substances 0.000 claims description 2
- 235000010447 xylitol Nutrition 0.000 claims description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 2
- 229960002675 xylitol Drugs 0.000 claims description 2
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 claims description 2
- 229920002148 Gellan gum Polymers 0.000 claims 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims 1
- 235000010492 gellan gum Nutrition 0.000 claims 1
- 239000000216 gellan gum Substances 0.000 claims 1
- 235000005772 leucine Nutrition 0.000 claims 1
- 238000012856 packing Methods 0.000 claims 1
- 229960000502 poloxamer Drugs 0.000 claims 1
- 238000004806 packaging method and process Methods 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 description 12
- 239000000843 powder Substances 0.000 description 9
- 239000012535 impurity Substances 0.000 description 8
- 239000004615 ingredient Substances 0.000 description 8
- 238000009472 formulation Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 238000004090 dissolution Methods 0.000 description 6
- 239000008187 granular material Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 4
- 238000003475 lamination Methods 0.000 description 4
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 229940015509 gabapentin 300 mg Drugs 0.000 description 2
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 239000005414 inactive ingredient Substances 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 235000019629 palatability Nutrition 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 102000038650 voltage-gated calcium channel activity Human genes 0.000 description 2
- 108091023044 voltage-gated calcium channel activity Proteins 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 101000782236 Bothrops leucurus Thrombin-like enzyme leucurobin Proteins 0.000 description 1
- 108090000312 Calcium Channels Proteins 0.000 description 1
- 102000003922 Calcium Channels Human genes 0.000 description 1
- 241000518994 Conta Species 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 239000007919 dispersible tablet Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000011363 dried mixture Substances 0.000 description 1
- 239000002706 dry binder Substances 0.000 description 1
- 230000005489 elastic deformation Effects 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 230000002964 excitative effect Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 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 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 230000002706 hydrostatic effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical class OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229960002160 maltose Drugs 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 229940100691 oral capsule Drugs 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 229940096978 oral tablet Drugs 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000003186 pharmaceutical solution Substances 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 210000005215 presynaptic neuron Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000007939 sustained release tablet Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 238000005550 wet granulation Methods 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- 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
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
-
- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Zoology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Medicinal Preparation (AREA)
Abstract
An orally disintegrating tablet comprising 30-70% w/w gabapentin, a diluent, 0.5-10% disintegrant and 0.5-3% stabiliser. The diluent may be 15-50% microcrystalline cellulose (MCC). At least 30% of the MCC may have a particle size of 70-100 µm and a bulk density of 0.26-0.34 g/ml or at least 70% may have a particle size below 75 µm and a bulk density of 0.1-0.15 g/ml. The diluent may be 5-30% maize starch or 15-55% of an MCC and maize starch combination. The orodispersable tablet may comprise binders, sweeteners and lubricants. Preferably, the disintegrant is crospovidone, stabiliser is poloxamer 407, lubricant is 0.5-4.5% magnesium stearate, binder is 0.5-6% hydroxypropyl cellulose and sweetener is 0.05-2% acesulfame potassium. The tablet may comprise magnesium stearate, hydroxypropyl cellulose, acesulfame potassium and crospovidone. The diluent and disintegrant may be in a ratio between 10:1 and 15:1. The tablet may be for treatment or prevention of postherpetic neuralgia and peripheral neuropathic pain. The tablet may dissolve in under 3 minutes, be stable for at least 3 months and be produced by sieving and mixing gabapentin and maize starch, blending with sieved MCC, crospovidone, hydroxypropyl cellulose, poloxamer 407, acesulfame potassium and magnesium stearate, compressing into a tablet and packaging.
Description
An Orally disintegrating tablet conta' * g Gabapentin or pharmaceutically acceptable salts thereof and the process of preparing the same
Field of the Invention
The present invention relates to a pharmaceutical composition of Gabapentin. The present invention relates to an orally disintegrating tablet of Gabapentin or pharmaceutically acceptable salts thereof for oral administration. The present invention also relates to the process of the preparation of the same
Background of the Invention
Gabapentin was first disclosed in the US 4024175. Gabapentin is a structural analogue of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).
The primary mode of action appears to be at the auxiliary a25-1 subunit of voltage- gated calcium channels The major function of these subunits is to facilitate the movement of pore-forming a28-1 subunits of calcium channels from the endoplasmic reticulum to the cell membrane of pre-synaptic neurons. Gabapentin appears to inhibit the action of a28-1 subunits, thus decreasing the density of pre-synaptic voltage-gated calcium channels and the subsequent release of excitatory neurotransmitters.
Gabapentin is indicated for the treatment of postherpetic neuralgia and various types of peripheral neuropathic pain, such as painful diabetic neuropathy in adults and partial-onset seizures in paediatrics The 1UPAC name of gabapentin is 2-[]-(amino methyl) cyclohexyllacetic acid. The plasma half-life of gabapentin in patients with normal renal function is 5-7 hours Gabapentin is a high-water solubility and low permeability drug which makes it belong to BCS Class-Ill in the Biopharmaceutical classification system.
Gabapentin is marketed, particularly as an oral tablet, capsule, or solution. The commercially marketed products of Gabapentin in tablet form are available in five dosage strengths: 100, 300, 400, 600, and 800 mg for oral administration. Orally disintegrating tablets provides a good mouth feel property that improves patient compliance, particularly for paediatric patients. Moreover, Gabapentin is a freely water-soluble drug, making it a suitable drug for orally disintegrating tablet.
The marketed tablet of gabapentin is available in large size which is difficult to swallow for elderly, paediatrics resulting in patient noncompliance Therefore, Gabapentin is a good candidate for formulating the orally dispersible tablet as it is easy to swallow and would provide patient compliance for paediatrics, geriatric and psychiatric patients disabled bedridden patients, and for traveling and busy people, who do not have ready access to water or difficulty in swallowing.
The orally disintegrating tablet of the present invention is a pharmaceutical formulation that rapidly disintegrates in the mouth which helps in easy administration of tablet and provide accurate dosing as compared to liquid formulations.
EP 1784174A1 discloses a stable pharmaceutical composition comprising gabapentin as the active ingredient, tribasic calcium phosphate as a sliding agent, hydrogenated castor oil as a lubricant, sorbitol and alginic acid in mixture as diluents. The manufacturing process of invention involves a mixture of powders of gabapentin and inactive ingredients are mixed properly in a mixer for 10 minutes at room temperature The final powder mixture thus obtained are filled into capsules EP2923694A1 discloses a liquid pharmaceutical solution comprising gabapentin or a pharmaceutically acceptable salt, solvate, or hydrate thereof and one or more pharmaceutically acceptable excipients. The manufacturing process of this invention is carried out under nitrogen gas as follows: A Tank filled with water, to this Maltitol solution, is added Thereafter, sodium benzoate and di sodium EDTA as an antioxidant are added to this solution and mixed to obtain a homogeneous mixture and then Gabapentin is added to this pre-mixed solution Mixing other excipients to the final solution to achieve complete dissolution of ingredients. The final mixture is filtrated and filled into bottles.
EP1558218A1 discloses the conventional tablet comprising gabapentin and one or more excipients. The manufacturing process of this invention involves a wet granulation method as per following steps: a first portion of a binder is added to dried mixture of gabapentin and one or more excipients as combination or in separate way. To the dried granules, a second portion of binder in solution or dispersion form is added, followed by drying granules and then compressing dried granules into tablets.
EP1513504A1 discloses the sustained-release tablet comprises gabapentin or a pharmaceutically acceptable salt or hydrates thereof and at least one rate-controlling polymer. The manufacturing process of this invention involves forming granules by mixing gabapentin with rate-controlling polymer and inactive ingredients, a water or binder solution is added to pre-mixed granules followed by drying the wet granules and compressed into tablets which provides gabapentin release for up to 12 hours.
1JS20090176882A1 discloses the gastric retentive oral dosage form of gabapentin for once or twice daily dose administration for improving patient compliance The process of this invention involves dispersing gabapentin in hydrophilic polymer that upon ingestion into gastric fluid swells to a size sufficient to achieve retention of the dosage form in the stomach in a fed mode for a period of at least about five hours
Summary of the Invention
The present invention provides an orally disintegrating tablet that comprises Gabapentin or phannaceutically acceptable salts thereof, Gabapentin is a good candidate for formulating orally disintegrating tablet that can provide good palatability and taste-masking properties for improving patient compliance.
Another embodiment of the invention provides the orally disintegrating tablet containing Gabapentin or pharmaceutically acceptable salts thereof, the diluent, and at least one or more ingredient such as a binder, a disintegrant, a stabilizer, a lubricant and a sweetener.
Further, another embodiment of the present invention that involves a process for preparing the orally disintegrating tablet. The orally disintegrating tablet is 15 manufactured by the direct compression method.
Another embodiment of the present invention can effectively treat postherpetic neuralgia and various types of peripheral neuropathic pain, such as painful diabetic neuropathy in adults and partial-onset seizures in paediatrics.
Obiects of the Invention The principal object of the present invention is to provide an orally disintegrating tablet of Gabapentin or pharmaceutically acceptable salts thereof It is further another object of the present invention to provide fast disintegration and dissolution of the dosage form as it gets in contact with saliva.
Yet another object of the present invention is to provide taste-masking properties and present pleasant palatability for paediatrics and also for administration to patients who cannot swallow, like the elderly, stroke victims, and bedridden patients; who do not have ready access to water.
Detailed description of the Invention
The present invention is an orally disintegrating tablet suitable for oral administration comprising gabapentin or pharmaceutically acceptable salts thereof with fast disintegrating properties as compared to conventional solid dose forms.
As per one embodiment of the present invention, gabapentin or pharmaceutically acceptable salts thereof, is present in the range of about 30%w/w to about 70%w/w, preferably in the range of about 40%w/w to about 60%w/w.
The term "about", as and when used in this specification, means +10 % of the mentioned value.
As per one embodiment of the present invention, the composition comprises a diluent selected from the group consisting of spray-dried lactose, dicalcium phosphate, dextrates, microciystalline cellulose, dextrose, maize starch, fructose, Sorbitol, pregelatinized starch, starch, xylitol, sucrose, Sorbitol, maltodextrin, maltose, mannitol or combinations thereof In the present invention, combination of microcrystalline cellulose and maize starch is preferred as a diluent in the range of about 15%w/w to about 55%w/w, preferably in the range from about 30%w/w to about 45%w/w. Microcrystalline cellulose is present in the range of about 15%w/w to about 50%w/w, preferably in the range from about 20%w/w to about 40%w/w and maize starch is present in the range from about 5%w/w to about 30%w/w, preferably in the range from about 7.0%w/w-to about 25.0%w/w. Maize Starch is used as a diluent as starches are known to swell upon contact with water through a wicking mechanism. Microcrystalline cellulose has a fast-wicking rate of water and small elastic deformation. The combination of microcrystalline cellulose and maize starch as diluents can provide fast disintegrating properties to the tablets.
As per another embodiment of the present invention, 30% of total weight of microcrystalline cellulose, which is characterized in that the average particle size of the microcrystalline cellulose particle is the range from about 70 nm to about 100 nm, preferably from about 90 nm to about 100 nm and the bulk density is in the range from about 0.26g/m1 to about 0.34 g/ml, preferably in the range from about 0.30g/m1 to about 0.33g/m1 and remaining 70% of microcrystalline cellulose, which is characterized in that the particle size of the microcrystalline cellulose is lesser than 75 ttm preferably lesser than 70 p.m and the bulk density is in the range from about 0.10g/cm3 to about 0.15 g/cm3, preferably in the range from about 0.11g/cm3to about 0.14g/cm3.
As per one more embodiment of the present invention, the disintegrant selected from the group consisting of Modified starches, cross-linked polyvinylpyrrolidone, croscarmellose sodium, soy polysaccharide, Cross-linked alginic acid, gell an gum, calcium Silicate or combinations thereof Crospovidone is preferred as a disintegrant for the present invention in the range from about 0.5%w/w to about 10.0%w/w, preferably in the range from about 1.5%w/w to about 7.5%w/w. Crospovidone quickly wicks saliva into the tablet to generate the volume expansion and hydrostatic pressures necessary to provide rapid disintegration in the mouth.
As per one embodiment of the present invention, a stabilizing agent selected from the group consisting of Poloxamers, Amino acid-based stabilizers, sodium alginate, sodium carboxymethyl cellulose (CMC), guar gum, locust bean gum, carrageenan, gelatin, and pectin, Povidone, Polyvinyl alcohol, sodium lauryl sulfate or combinations thereof Poloxamer 407 is preferred as stabilizer for the present invention. Poloxamer 407 is present in the range from about 0.5%w/w to about 3.0%w/w, preferably in the range from about 1.0%w/w to about 2.0')/ow/w.
As per one another embodiment of the present invention, a lubricant selected from the group consisting of boric acid, magnesium stearate, sodium stearyl fumarate, micronized poly oxy ethylene glycol, leuc ne, sodium benzoate, sodium acetate, sodium lauryl sulfate, stearic acid, sodium stearate, sodium oleate, calcium stearate, waxes or combinations thereof Magnesium stearate is preferred as a lubricant for the present invention and is present in the range from about 0.5%w/w to about 4.5% w/w, preferably in the range from about I.0%w/w to about 2.5%w/w.
As per one more embodiment of the present invention, a sweetener selected from the group consisting of cyclamate, acesulfame potassium, neo hesperidin dihydrochalcone, monoammonium glycyrrhizinate, saccharin sodium, sucralose, saccharin, aspartame or combinations thereof Acesulfame potassium is preferred as a sweetener for the present invention. Acesulfame potassium is present in the range from about 0.05w/w to about 2%w/w, preferably in the range from about 0.30%w/w to about I.5%w/w.
As per one embodiment of the present invention, a suitable binder for the present invention can be selected from the group consisting of alginic acid, carbomer, ethyl cellulose, gelatin, glucose, guar gum, hydroxy ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose, polydextrose, polyethylene oxide, and povidone K30 or combinations thereof Hydroxypropyl cellulose is preferred as a binder for the present invention. Hydroxypropyl cellulose is present in the range from about 0.5% w/w to about 6.0% w/w, preferably in the range from about 1 %w/w to about 3 %w/w.
As per one another embodiment of the present invention, the orally disintegrating tablet comprising Gabapentin or pharmaceutically acceptable salts thereof is present in the range from about 30%w/w to about 70%w/w, preferably in the range from about 40%w/w-to about 60%w/w, a disintegrant present in the range from about 0.5 %w/w to about 10% w/w preferably in the range from about 1.5 %w/w to about 7.5%w/w and a diluent is present in the range from about 15%w/w to about 55%w/w, preferably in the range from about 30%w/w to about 45%w/w. The orally disintegrating tablet further comprises at least one pharmaceutically acceptable excipient selected from sweeteners, binders, stabilizers, lubricants or combination thereof As per preferred embodiment of the present invention, the orally disintegrating tablet comprising Gabapentin or pharmaceutically acceptable salts thereof is present in the range from about 30%w/w to about 70%w/w, preferably in the range from about 40%w/w to about 60%w/w, Crospovidone is present in the range from about 0.5 %w/w to about 10% w/w preferably in the range from about 1.5 %w/w to about 7.5%w/w and a combination of Microcrystalline cellulose and maize starch is present in the range from about 15%w/w to about 55%w/w, preferably in the range from about 30%w/w to about 45%w/w. The orally disintegrating tablet further comprises at least one pharmaceutically acceptable excipient selected from Acesulfame potassium, 1-Tydroxypropyl cellulose, Poloxamer 407 and Magnesium Stearate.
As per one embodiment of the present invention, the ratio of diluent to di sintegrant is in the range of 10:1 to 15:1 and preferably it is in the range of 12:1 to 14:1. As per preferred embodiment of the present invention, the ratio of combination of Microcrystalline cellulose and Maize Starch to Crospovidone is in the range of 10:1 to 15:1 and preferably it is in the range of 12:1 to 14: 'Increase in amount of disintegrant Crospovidone caused a decrease in disintegration time whereas amount of maize starch was changed in different batches and microcrystalline cellulose was kept constant The ratio of microcrystalline cellulose and maize starch to Crospovidone is optimized in order to achieve fast disintegration of tablet.
As per one embodiment of the present invention, the process for the preparation of orally disintegrating tablets containing Gabapentin or salts thereof, by direct compression method which is one of the most economical methods. The direct compression method is primarily used as it requires fewer processing steps and less equipment. Therefore, the method is potentially less expensive than other methods used in tablet manufacture.
As per one embodiment of the present invention, the disintegrating time of the Gabapentin orally disintegrating tablet is not more than 3 minutes, preferably less than 50 seconds.
As per one embodiment of the present invention, more than 90% of the Gabapentin is released in 15 minutes, preferably more than 90% is released within 10 minutes.
As per one embodiment of the present invention, packaging material for Orally disintegrating tablet of Gabapentin is selected from the Polypropylene Bottle with Silica canister, PP Bottle with Oxygen scavenger, HDPE Bottle, HDPE Bottle with Silica canister, HDPE Bottle with Oxygen scavenger, Alu-Alu Blister. In present invention, the HDPE Bottle with silica canister is preferred as packaging material over other packaging materials as it provided desired physical parameters like appearance of tablets and desired chemical parameters like lesser impurities on storage for 3 months.
As per one embodiment of the present invention, the orally disintegrating tablet of Gabapentin can be effective in the treatment of postherpetic neuralgia and various types of peripheral neuropathic pain, such as painful diabetic neuropathy in adults and partial-onset seizures in paediatrics.
As per one embodiment of the present invention, the orally disintegrating tablet is manufactured by direct compression. Gabapentin, maize starch, microcrystalline cellulose, crospovidone, hydroxypropyl cellulose, Poloxamer 407 and acesulfame potassium were sieved separately through 40# sieve. Magnesium Stearate was sieve separately through 60# sieve. Sifted quantity of Gabapentin, maize starch was mixed properly for 15 minutes in blender. To this powder mixture, microcrystalline cellulose, crospovidone, hydroxypropyl cellulose, acesulfame potassium and poloxamer 407 were added and mixed in blender for 15 minutes and then magnesium stearate was added to the pre-lubricated blend and mixed in a blender for 5 minutes. Finally, the lubricated mixture is compressed to form tablets. The prepared tablets were packed in HDPE Bottles with silica canister as it provided good physical parameters and chemical parameters like impurities were found to be lesser as compared to other packaging materials in stability studies for 3 months.
The invention is further illustrated by the following examples, which are by no means intended to limit the scope of the invention but are given by way of illustration.
Example 1:
The Orally disintegrating tablet was made according to the method defined below using the formulation having the ingredients shown in table-I for different dose strengths that are 100 mg, 300mg, 400mg, 600mg and 800mg of gabapentin:
TABLE-I
Manufacturing process: Gabapentin, microcrystalline cellulose, maize starch, crospovidone and Acesulfame potassium were sieved separately through 40# sieve. Magnesium Stearate was sieved separately through 60# sieve. Sifted quantity of gabapentin, maize starch were mixed properly for 15 minutes in blender. To this powder mixture, sifted quantity of crospovidone, microcrystalline cellulose and acesulfame potassium were added and mixed in blender for 15 minutes and then magnesium Gabapentin 54.5 Maize Starch 15.9 Microcrystalline cellulose 26.8 Crospovidone 1.8 Acesulfame potassium 0.3 Magnesium stearate 0.7 Total stearate was added to the pre-lubricated blend and mixed in a blender for 5 minutes Finally, the lubricated mixture is compressed to form tablets.
Weight variation observed due to poor blend flow. In order to optimize blend flow, it was necessary to increase the concentration of Lubricant.
Example 2:
The Orally disintegrating tablet was made according to the method defined below using the formulation having the ingredients shown in table II for different dose strengths that are 100 mg, 300mg, 400mg, 600mg and 800mg of gabapentin:
TABLE -II
Bulk Density (gm/m1) 0.4475 Tap Density (gm/m1) 0.6712 Carr Index (/o) 33.33 Hausner Ratio 1.50 :MiM=UMN:M=MM JiatitioreffiellItcaaa Gabapentin 54.5 Maize Starch 15.5 Microcrystalline cellulose 26.8 Crospovidone 1.8 Acesulfame potassium 0.3 Magnesium stearate 1.1 Total 100.0 Manufacturing process: Gabapentin, mi crocry stall i ne cellulose, maize starch, crospovi done, and acesulfame potassium were sieved separately through 40# sieve. Magnesium Stearate was sieved separately through 60# sieve. Sifted quantity of Gabapentin, Maize starch were mixed properly for 15 minutes in blender. To this powder mixture, crospovidone, microcrystalline cellulose and acesulfame potassium were added and mixed in blender for 15 minutes and then magnesium stearate to the pre-lubricated blend was added and mixed in a blender for 5 minutes. Finally; the lubricated mixture is compressed to form tablets.
Flow properties increased but tablet lamination observed during compression. In order to remove lamination issue, it was necessary to add Hydroxypropyl Cellulose as a dry binder.
Bulk Density (gm/ml) 0.4320 Tap Density (gm/m1) 0.5865 Carr Index (%) 26.34 Hausner Ratio 1.35
Example 3:
The Orally disintegrating tablet was made according to the method defined below using the formulation having the ingredients shown in table Ell for different dose strengths that are 100 mg, 300mg, 400mg, 600mg and 800mg of gabapentin:
TABLE -III
Gabapentin 54.5 Maize Starch 14.58 MicrocrystaIline cellulose 26.8 Crospovidone 1.8 Acesulfame potassium 0.3 Hydroxypropyl Cellulose 0.9 Magnesium stearate 1.1 Total 100.0 Manufacturing process: Gabapentin, microcrystalline cellulose, maize starch, crospovidone, hydroxypropyl cellulose and acesulfame potassium were sieved separately through 40# sieve.
Magnesium Stearate was sieved separately through 60# sieve. Sifted quantity of Gabapentin, maize starch were mixed properly for 15 minutes in blender. To this powder mixture microcrystalline cellulose, crospovidone, hydroxypropyl cellulose and acesulfame potassium were added and mixed in blender for 15 minutes and then magnesium stearate was added to the pre-lubricated blend and mixed in a blender for 5 minutes. Finally, the lubricated mixture is compressed to form tablets.
Still minor tablet lamination was observed. In order to minimize lamination issue, it was necessary to increase concentration of Hydroxypropyl cellulose.
Example 4:
The Orally disintegrating tablet was made according to the method defined below using the formulation having the ingredients shown in table W for different dose strengths that are 100 mg, 300mg, 400mg, 600mg and 800mg of gabapentin:
TABLE -IV
Gabapentin 54.5 Maize Starch 13.67 Microcrystalline cellulose 26.8 Crospovidone 1.8 Acesulfame potassium 0.3 Hydroxypropyl Cellulose 1.8 Magnesium stearate 1.1 Total 100.0 Manufacturing process: Gabapentin, microcrystalline cellulose, Maize starch, crospovi done, hydroxypropyl cellulose and acesulfame potassium were sieved separately through 40# sieve. Magnesium Stearate was sieved separately through 60# sieve. Sifted quantity of gabapentin, maize starch were mixed properly for 15 minutes in blender. To this powder mixture, microcrystalline cellulose, crospovidone, hydroxypropyl cellulose and acesulfame potassium were added and mixed in blender for 15 minutes and then magnesium stearate was added to the pre-lubricated blend and mixed in a blender for 5 minutes. Finally, the lubricated mixture is compressed to form tablets Disintegration time observed higher side than usual In order to decrease disintegration time, it was necessary to increase concentration of di sintegrant.
Example 5:
The Orally disintegrating tablet was made according to the method defined below using the formulation having the ingredients shown in table V for different dose 15 strengths that are 100 mg, 300mg, 400mg, 600mg and 800mg of gabapentin:
TABLE -V g:
Gabapentin 54.5 Maize Starch 12.76 Microcrystalline cellulose 26.8 Crospovidone 2.7 Acesulfame potassium 0..3 Hydroxypropyl Cellulose 1.8 Magnesium stearate 1.1 Total 100.0 Manufacturing process: Gabapentin, microcrystalline cellulose, maize starch, crospovidone, hydroxypropyl cellulose and acesulfame potassium were sieved separately through 40# sieve.
Magnesium Stearate was sieve separately through 60# sieve. Sifted quantity of gabapentin, maize starch were mixed properly for 15 minutes in blender. To this powder mixture Microcrystalline cellulose, crospovidone, microcrystalline cellulose, hydroxypropyl cellulose and acesulfame potassium were added and mixed in blender for 15 minutes and then magnesium stearate was added to the pre-lubricated blend and mixed in a blender for 5 minutes. Finally, the lubricated mixture is compressed to form tablets.
All the physical parameters of tablets were found to be satisfactory but chemical parameters of tablets were found not satisfactory after 1-month stability data of Related Substances. In order to stabilize formulation during stability, it was necessary to add stabilizer as a Poloxamer 407.
Bulk Density (gm/ml) 0.4130 Tap Density (gm/me 0.5531 Carr Index (%) 25.32 Hausner Ratio 1.33
Example 6:
The Orally disintegrating tablet was made according to the method defined below using the formulation having the ingredients shown in table VI for different dose strengths that are 100 mg, 300mg, 400mg, 600mg and 800mg of gabapentin:
TABLE-VT
Gabapentin 54.5 Maize starch 10.95 Microcrystalline cellulose 26.73 Crospovidone 2.73 Acesulfame potassium 0.33 Poloxamer 407 1.81 Hydroxy Propyl Cellulose 1.81 Magnesium stearate 1.09 Total 100.0 Manufacturing process: Gabapentin, maize starch, microcrystalline cellulose, crospovidone, hydroxypropyl cellulose, poloxamer 407 and acesulfame potassium were sieved separately through 40# sieve. Magnesium Stearate was sieve separately through 60# sieve. Sifted quantity of gabapentin, maize starch were mixed properly for 15 minutes in blender. To this powder mixture, microcrystalline cellulose, crospovidone, hydroxypropyl Cellulose, acesulfame potassium and poloxamer 407 were added and mixed in blender for 15 minutes and then magnesium stearate was added to the pre-lubricated blend and mixed in a blender for 5 minutes. Finally, the lubricated mixture is compressed to form tablets. The prepared tablets were packed in I1DPE Bottles with silica canister as it provided good physical parameters and chemical parameters like impurities were found to be lesser as compared to other packaging materials in stability studies for 3 months.
All the physical and chemical parameters of tablets were found satisfactory after 3-month stability data as per below results: Bulk Density (gm/m1) 0.4075 Tap Density (gm/m1) 0.5314 Car Index (%) 23.31 Hausner Ratio 1.30 Example 7: The Dissolution profile of the tablet prepared according to
Example 6.
The conditions of dissolution are as following: Product Name: Gabapentin 300 mg orally disintegrating tablet Media: 0.1 N HCI Apparatus & RPM: Apparatus II (Paddle) Rate of rotation: 50 RPM Volume: 900 ml Temperature 37°C Detection: High performance liquid chromatography equipped with UV/PDA Detector at 210 nm The orally disintegrating tablet of Gabapentin was tested for its dissolution profile measured in 900mL of 0.1 N HC1 at 50 RPM in USP II (Paddle) apparatus and active ingredient of the tablet is released in more than 90% in 10 minutes.
Example 8: The orally disintegrating tablets prepared according to example 6 were subjected to a stability study of 25°C/60% RH for 3 months. The stability study was performed for 300 mg dose strength of Gabapentin Results are tabulated below.
Gabapentin 300 mg orally disintegrating tablet Hardness 30N-100N (Target 45N) 46N 38N Average weight 550.0 mg ± 5% (522.5 mg -577.5mg) 552.4mg 551.4mg Thickness 4.50 ± 0.30 mm (4.20mm to 4.80mm) 4.53mm 4.52 mm Friability Not more than 1.0% 0.29% 0.29% Disintegration time Not more than 3 minutes 14 sec 22sec Dissolution NLT 75% (Q) labelled 98.9 97.6 amount of Gabapentin should be dissolve in 15 minutes.
Assay (%) 95.0-105.0 % 100.0 101.4 Impurities (%)
RS-A
Impurity A Not more than 0.4% 0.051 0.0572 Single maximum Not more than 0.1% ND ND unknown impurity
RS-B
Single maximum Not more than 0.05% ND ND unknown impurity Total impurities for RS-A and RS-B Not more than 1.0% 0.051 0.0572
Claims (1)
- Claims: 1.An orally disintegrating tablet of Gabapentin for oral administration comprising: a) Gabapentm or pharmaceutically acceptable salts thereof, present in the range of about 30%w/w to about 70%w/w, preferably in the range from about 40%w/w to about 5 60%w/w; b) at least one diluent; c) at least one disintegrant present in the range from about 0.5%w/w to about 10.0%w/w, preferably in the range from about 1.5%w/w to about 7.5%w/w; and d) at least one stabilizer present in the range from about 0.5 %w/w to about 3.0 %w/w, 10 preferably in the range of about I.0%w/w to about 2.0 %w/w.2.The orally disintegrating tablet according to claim 1, wherein the diluent is selected from the group consisting of spray-dried lactose, dicalcium phosphate, dextrates, microcrystalline cellulose, dextrose, maize starch, fructose, sorbitol, pregelatinized starch, starch, xylitol, sucrose, sorbitol, maltodextrin, maltose, mannitol or combinations thereof 3.The orally disintegrating tablet according to claim 2, wherein the diluent is microcrystalline cellulose present in the range from about 15%w/w to about 50%w/w, preferably in the range from about 20%w/w to about 40%w/w.4.The orally disintegrating tablet according to claim 2, wherein at least 30% of the total weight of microcrystalline cellulose has an average particle size in the range from about pm to about 100 tm, preferably in the range from about 90 i.irn to about 100 [Lin and the bulk density is in the range from about 0.26g/m1 to about 0.34g/ml, preferably in the range from 0.30g/m1 to about 0.33g/ml.5.The orally disintegrating tablet according to claim 2, wherein at least 70% of the total weight of microciystalline cellulose has a particle size lesser than 75 gm, preferably lesser than 70 gm and the bulk density is in the range from about 0.10 g/cm3 to about 0.15 g/cm3, preferably from about 0.11 g/cm3 to about 0.14g/cm3.6.The orally disintegrating tablet according to claim 2, wherein the diluent is Maize Starch present in the range from about 5%w/w to about 30%w/w, preferably in the range from about 7 %w/w to about 25 %w/w.7.The orally disintegrating tablet according to claim 1, wherein the diluent is the combination of microcrystalline cellulose and Maize starch present in the range from 10 about 15%w/w to about 55 %w/w, preferably in the range from about 30% w/w to about 45%w/w.8.The orally disintegrating tablet according to claim 1, wherein the disintegrant is selected from the group consisting of modified starches, cross-linked polyvinylpyrrolidone, croscarmellose sodium, soy polysaccharide, cross-linked alginic acid, gellan gum, calcium silicate or combinations thereof 9.The orally disintegrating tablet according to claim 8, wherein the disintegrant is Crospovidone.10.The orally disintegrating tablet according to claim 1, wherein the stabilizer is selected from the group consisting of Poloxamers, Amino acid-based stabilizers, sodium alginate, sodium carboxymethyl cellulose (CMC), guar gum, locust bean gum, carrageenan, gelatin, and pectin, Povidone, Polyvinyl alcohol, Sodium lauryl sulfate or combinations thereof.11 The orally disintegrating tablet according to claim 10, wherein the stabilizer is Poloxamer 407.12.The orally disintegrating tablet according to claim 1, wherein pharmaceutical composition further comprises at least one or more pharmaceutically acceptable excipients are selected from the group consisting of binders, sweeteners, and lubricants or combinations thereof 13.The orally disintegrating tablet according to claim 12, wherein the lubricant is selected from the group consisting of boric acid, magnesium stearate, Sodium Stearyl fumarate, micronized poly oxy ethylene glycol, leucine, sodium benzoate, sodium acetate, sodium lauryl sulfate, stearic acid, sodium stearate, sodium oleate, Poloxamer 407, calcium stearate, waxes or combinations thereof.14.The orally disintegrating tablet according to claim 12, wherein the lubricant is Magnesium Stearate is present in the range from about 0.5%w/w to about 4.5%w/w, preferably in the range from about 1.0%w/w to about 2.5%w/w.15.The orally disintegrating tablet according to claim 12, wherein the binder is selected from the group consisting of alginic acid, carbomer, ethyl cellulose, gelatin, glucose, guar gum, hydroxy ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methyl cellulose, polydextrose, polyethylene oxide, and Povidone K30 or combinations thereof.16.The orally disintegrating tablet according to claim 12, wherein the binder is hydroxypropyl cellulose present in the range from about 0.5% w/w to about 6.0% w/w, preferably in the range from about 1 %w/w to about 3 %w/w.17.The orally disintegrating tablet according to claim 12, wherein the sweetener is selected from the group consisting of cyclamate, acesulfame potassium, neo hesperidin dihydrochalcone, monoammonium glycyrrhizinate, saccharin sodium, sucralose, saccharin, aspartame or combinations thereof.18.The orally disintegrating tablet according to claim 12, wherein the sweetener is acesulfame potassium present in the range from about 0.05 %w/w to about 2 %w/w, preferably in the range from about 0.30 %w/w to about 1.5 %w/w.I 9.The orally disintegrating tablet according to claim I, further comprises magnesium stearate, hydroxypropyl cellulose, Acesulfame potassium, and Crospovidone.20.The orally disintegrating tablet according to claim 1, wherein the ratio of a diluent to disintegrant is in the range of 10:1 to 15:1 and preferably in the range of 12:1 to 14:1.21 The orally disintegrating tablet according to claim I, wherein the orally disintegrating tablet is manufactured by the direct compression method comprising the steps of (a)Sieving separately Gabapentin, microcrystalline cellulose, maize starch, crospovidone, Hydroxy Propyl Cellulose, Poloxamer 407, and Acesulfame potassium through 40# sieve and magnesium Stearate separately through 60# sieve: (b)Mixing of the previously sifted quantity of gabapentin and Maize starch for 15 minutes in a blender; (c)Blending the sifted quantity of microcrystalline cellulose, crospovidone, hydroxy propyl cellulose, poloxamer 407, and Acesulfame potassium in the blender with step-(b) for 15 minutes in blender; (d) Adding magnesium stearate to the pre-lubricated blend of step-(c) in a blender for 5 minutes; (e) Compressing the resulting mixture into a tablet; and (f) packing of the tablet into HDPE Bottles with silica canister.22. The orally disintegrating tablet according to claim 1, wherein the orally disintegrating tablet is disintegrated in the buccal cavity upon contact with saliva in less than 3 minutes, preferably less than 50 seconds 23. The orally disintegrating tablet according to claim I, is for the treatment or prevention of postherpetic neuralgia and various types of peripheral neuropathic pain such as painful diabetic neuropathy in adults and partial-onset seizures in pediatrics.24. The orally disintegrating tablet according to claim I, wherein the packaging material of the container is selected from the Polypropylene Bottle with Silica canister, PP Bottle with Oxygen scavenger, 1-1DPE Bottle, 1-1TWE Bottle with Silica canister, HOPE. Bottle with Oxygen scavenger, Alu-Alu Blister.25. The orally disintegrating tablet according to claim 24, wherein the tablet is more stable for at least three months at 25°C and 60% relative humidity in HOPE Bottle with a Silica canister.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB2219356.9A GB2625579A (en) | 2022-12-21 | 2022-12-21 | An orally disintegrating tablet containing gabapentin or pharmaceutically acceptable salts thereof and the process of preparing the same |
PCT/GB2023/053353 WO2024134210A1 (en) | 2022-12-21 | 2023-12-21 | An orally disintegrating tablet containing gabapentin or pharmaceutically acceptable salts thereof and the process of preparing the same |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB2219356.9A GB2625579A (en) | 2022-12-21 | 2022-12-21 | An orally disintegrating tablet containing gabapentin or pharmaceutically acceptable salts thereof and the process of preparing the same |
Publications (2)
Publication Number | Publication Date |
---|---|
GB202219356D0 GB202219356D0 (en) | 2023-02-01 |
GB2625579A true GB2625579A (en) | 2024-06-26 |
Family
ID=85035991
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB2219356.9A Pending GB2625579A (en) | 2022-12-21 | 2022-12-21 | An orally disintegrating tablet containing gabapentin or pharmaceutically acceptable salts thereof and the process of preparing the same |
Country Status (2)
Country | Link |
---|---|
GB (1) | GB2625579A (en) |
WO (1) | WO2024134210A1 (en) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20020012679A1 (en) * | 1998-08-03 | 2002-01-31 | Societe Laboratoires Des Produits Ethiques - Ethypharm | Process for manufacturing coated gabapentin or pregabalin particles |
WO2004089343A1 (en) * | 2003-04-09 | 2004-10-21 | Ranbaxy Laboratories Limited | Water soluble tablets |
CN101305987A (en) * | 2007-05-17 | 2008-11-19 | 北京利乐生制药科技有限公司 | Compound gabapentin mecobalamin dispersible tables and preparation method thereof |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2460891C2 (en) | 1974-12-21 | 1982-09-23 | Gödecke AG, 1000 Berlin | 1-aminomethyl-1-cycloalkaneacetic acids and their esters, processes for their preparation and medicaments containing these compounds |
WO2003103634A1 (en) | 2002-06-07 | 2003-12-18 | Ranbaxy Laboratories Limited | Sustained release oral dosage forms of gabapentin |
WO2004032905A1 (en) | 2002-10-08 | 2004-04-22 | Ranbaxy Laboratories Limited | Gabapentin tablets and methods for their preparation |
ITMI20041447A1 (en) | 2004-07-20 | 2004-10-20 | Zambon Spa | PHARMACEUTICAL COMPOSITION INCLUDING GABAPENTINA |
US20090176882A1 (en) | 2008-12-09 | 2009-07-09 | Depomed, Inc. | Gastric retentive gabapentin dosage forms and methods for using same |
ES2288117B1 (en) * | 2006-05-08 | 2008-12-01 | Combino Pharm, S.L. | SOLID PHARMACEUTICAL COMPOSITION OF GABAPENTINA. |
WO2015144825A1 (en) | 2014-03-27 | 2015-10-01 | Sanovel Ilac Sanayi Ve Ticaret A.S. | Oral liquid pharmaceutical solution of gabapentin |
-
2022
- 2022-12-21 GB GB2219356.9A patent/GB2625579A/en active Pending
-
2023
- 2023-12-21 WO PCT/GB2023/053353 patent/WO2024134210A1/en unknown
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20020012679A1 (en) * | 1998-08-03 | 2002-01-31 | Societe Laboratoires Des Produits Ethiques - Ethypharm | Process for manufacturing coated gabapentin or pregabalin particles |
WO2004089343A1 (en) * | 2003-04-09 | 2004-10-21 | Ranbaxy Laboratories Limited | Water soluble tablets |
CN101305987A (en) * | 2007-05-17 | 2008-11-19 | 北京利乐生制药科技有限公司 | Compound gabapentin mecobalamin dispersible tables and preparation method thereof |
Non-Patent Citations (1)
Title |
---|
Pharmaceutical development and technology, vol. 25, no. 2, 2019, Soliman, I. et al., "Gabapentin-saccharin co-crystals with enhanced physicochemical properties and in vivo absorption formulated as oro-dispersible tablets.", p. 227-236. * |
Also Published As
Publication number | Publication date |
---|---|
WO2024134210A1 (en) | 2024-06-27 |
GB202219356D0 (en) | 2023-02-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US9730896B2 (en) | Orally disintegrating tablets and methods of manufacture | |
RU2456989C2 (en) | Solid dosage forms containing tadalafil | |
KR101965002B1 (en) | Rapidly dispersing granules, orally disintegrating tablets and methods | |
EP2170295B1 (en) | Improved pharmaceutical composition containing dihydropyridine calcium channel antagonist and method for the preparation thereof | |
EP2448561B1 (en) | Solid pharmaceutical fixed dose compositions comprising irbesartan and amlodipine, their preparation and their therapeutic application | |
WO2015131269A1 (en) | Orally disintegrating tablet of nabilone comprising mannitol-based granules | |
US8951504B2 (en) | (trimethoxyphenylamino) pyrimidinyl formulations | |
GB2625579A (en) | An orally disintegrating tablet containing gabapentin or pharmaceutically acceptable salts thereof and the process of preparing the same | |
EP2903593B1 (en) | Tablet containing composite with cyclodextrin | |
EP2925320B1 (en) | Novel method for improving the bioavailability of low aqueous solubility drugs | |
WO2024028262A1 (en) | Novel formulation | |
AU2016209466A1 (en) | Stable solid fingolimod dosage forms | |
JP2023039536A (en) | Orally disintegrating tablet | |
EP3843702A1 (en) | Immediate release fixed-dose combination of memantine and donepezil | |
PL241575B1 (en) | Preparation of bosentan in the form of orodispersible tablets |