KR102149080B1 - Orally Disintegrating Tablet comprising sugar or sugar alcohol granules reformed with ethyl cellulose - Google Patents
Orally Disintegrating Tablet comprising sugar or sugar alcohol granules reformed with ethyl cellulose Download PDFInfo
- Publication number
- KR102149080B1 KR102149080B1 KR1020180055753A KR20180055753A KR102149080B1 KR 102149080 B1 KR102149080 B1 KR 102149080B1 KR 1020180055753 A KR1020180055753 A KR 1020180055753A KR 20180055753 A KR20180055753 A KR 20180055753A KR 102149080 B1 KR102149080 B1 KR 102149080B1
- Authority
- KR
- South Korea
- Prior art keywords
- ethyl cellulose
- sugar
- disintegrating tablet
- housewife
- tableting
- Prior art date
Links
- 239000001856 Ethyl cellulose Substances 0.000 title claims abstract description 44
- 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 title claims abstract description 44
- 235000019325 ethyl cellulose Nutrition 0.000 title claims abstract description 44
- 229920001249 ethyl cellulose Polymers 0.000 title claims abstract description 44
- 239000008187 granular material Substances 0.000 title claims abstract description 36
- 150000005846 sugar alcohols Chemical class 0.000 title abstract description 26
- 235000000346 sugar Nutrition 0.000 title abstract description 24
- 239000006191 orally-disintegrating tablet Substances 0.000 title description 3
- 238000004519 manufacturing process Methods 0.000 claims abstract description 14
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 14
- 238000002360 preparation method Methods 0.000 claims abstract description 10
- 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 36
- 238000000034 method Methods 0.000 claims description 31
- 239000000203 mixture Substances 0.000 claims description 27
- -1 magnesium metasilicate aluminate Chemical class 0.000 claims description 25
- 235000010355 mannitol Nutrition 0.000 claims description 20
- 229920002261 Corn starch Polymers 0.000 claims description 13
- 239000008120 corn starch Substances 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 238000002156 mixing Methods 0.000 claims description 11
- 239000011230 binding agent Substances 0.000 claims description 8
- 239000007884 disintegrant Substances 0.000 claims description 7
- 229940079593 drug Drugs 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 claims description 7
- 235000012239 silicon dioxide Nutrition 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 5
- 229930195725 Mannitol Natural products 0.000 claims description 4
- 239000003086 colorant Substances 0.000 claims description 4
- 235000003599 food sweetener Nutrition 0.000 claims description 4
- 239000000314 lubricant Substances 0.000 claims description 4
- 239000000594 mannitol Substances 0.000 claims description 4
- 239000003765 sweetening agent Substances 0.000 claims description 4
- 238000005550 wet granulation Methods 0.000 claims description 4
- 239000000796 flavoring agent Substances 0.000 claims description 3
- 235000013355 food flavoring agent Nutrition 0.000 claims description 3
- 239000003002 pH adjusting agent Substances 0.000 claims description 3
- 239000003755 preservative agent Substances 0.000 claims description 3
- 230000002335 preservative effect Effects 0.000 claims description 3
- 239000003381 stabilizer Substances 0.000 claims description 3
- 239000004094 surface-active agent Substances 0.000 claims description 3
- 239000004088 foaming agent Substances 0.000 claims description 2
- 239000003205 fragrance Substances 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 230000007423 decrease Effects 0.000 abstract description 5
- 238000003860 storage Methods 0.000 abstract description 5
- 238000009826 distribution Methods 0.000 abstract description 3
- 230000007774 longterm Effects 0.000 abstract description 2
- 239000003826 tablet Substances 0.000 description 72
- 230000000052 comparative effect Effects 0.000 description 27
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- 239000000243 solution Substances 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 238000005469 granulation Methods 0.000 description 15
- 230000003179 granulation Effects 0.000 description 15
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 14
- 239000004698 Polyethylene Substances 0.000 description 13
- 229960000913 crospovidone Drugs 0.000 description 13
- 235000019359 magnesium stearate Nutrition 0.000 description 13
- 229920003023 plastic Polymers 0.000 description 13
- 239000004033 plastic Substances 0.000 description 13
- 229920000573 polyethylene Polymers 0.000 description 13
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 13
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 13
- 239000008213 purified water Substances 0.000 description 13
- 108010011485 Aspartame Proteins 0.000 description 12
- 239000000605 aspartame Substances 0.000 description 12
- 235000010357 aspartame Nutrition 0.000 description 12
- 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 description 12
- 229960003438 aspartame Drugs 0.000 description 12
- 239000006185 dispersion Substances 0.000 description 11
- WMGSQTMJHBYJMQ-UHFFFAOYSA-N aluminum;magnesium;silicate Chemical compound [Mg+2].[Al+3].[O-][Si]([O-])([O-])[O-] WMGSQTMJHBYJMQ-UHFFFAOYSA-N 0.000 description 8
- 239000007788 liquid Substances 0.000 description 7
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 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 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 239000012266 salt solution Substances 0.000 description 4
- 229940032147 starch Drugs 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 210000000214 mouth Anatomy 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 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 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 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 229920002785 Croscarmellose sodium Polymers 0.000 description 2
- 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 description 2
- 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 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 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 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 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 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 description 2
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 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 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000012790 confirmation Methods 0.000 description 2
- 229960001681 croscarmellose sodium Drugs 0.000 description 2
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 2
- 229960000520 diphenhydramine Drugs 0.000 description 2
- 238000001125 extrusion Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000001341 hydroxy propyl starch Substances 0.000 description 2
- 235000013828 hydroxypropyl starch Nutrition 0.000 description 2
- 239000000832 lactitol Substances 0.000 description 2
- 235000010448 lactitol Nutrition 0.000 description 2
- VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound 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-JVCRWLNRSA-N 0.000 description 2
- 229960003451 lactitol Drugs 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000000845 maltitol Substances 0.000 description 2
- 235000010449 maltitol Nutrition 0.000 description 2
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound 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 2
- 229940035436 maltitol Drugs 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 230000001953 sensory effect Effects 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000008109 sodium starch glycolate Substances 0.000 description 2
- 229920003109 sodium starch glycolate Polymers 0.000 description 2
- 229940079832 sodium starch glycolate Drugs 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 238000001694 spray drying Methods 0.000 description 2
- 238000013112 stability test Methods 0.000 description 2
- 230000009747 swallowing Effects 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 229940033134 talc Drugs 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
- 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 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 1
- 239000004604 Blowing Agent Substances 0.000 description 1
- 101100288387 Caenorhabditis elegans lab-1 gene Proteins 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- BIVBRWYINDPWKA-VLQRKCJKSA-L Glycyrrhizinate dipotassium Chemical compound [K+].[K+].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 BIVBRWYINDPWKA-VLQRKCJKSA-L 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 235000019501 Lemon oil Nutrition 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004373 Pullulan Substances 0.000 description 1
- 229920001218 Pullulan Polymers 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 description 1
- 239000004376 Sucralose Substances 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010358 acesulfame potassium Nutrition 0.000 description 1
- 229960004998 acesulfame potassium Drugs 0.000 description 1
- 239000000619 acesulfame-K Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- WLDHEUZGFKACJH-UHFFFAOYSA-K amaranth Chemical compound [Na+].[Na+].[Na+].C12=CC=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(O)=C1N=NC1=CC=C(S([O-])(=O)=O)C2=CC=CC=C12 WLDHEUZGFKACJH-UHFFFAOYSA-K 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- OIQPTROHQCGFEF-UHFFFAOYSA-L chembl1371409 Chemical compound [Na+].[Na+].OC1=CC=C2C=C(S([O-])(=O)=O)C=CC2=C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 OIQPTROHQCGFEF-UHFFFAOYSA-L 0.000 description 1
- 238000004581 coalescence Methods 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- JFVXEJADITYJHK-UHFFFAOYSA-L disodium 2-(3-hydroxy-5-sulfonato-1H-indol-2-yl)-3-oxoindole-5-sulfonate Chemical compound [Na+].[Na+].Oc1c([nH]c2ccc(cc12)S([O-])(=O)=O)C1=Nc2ccc(cc2C1=O)S([O-])(=O)=O JFVXEJADITYJHK-UHFFFAOYSA-L 0.000 description 1
- 239000003844 drug implant Substances 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N ferric oxide Chemical compound O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 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
- 229940049654 glyceryl behenate Drugs 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000010501 lemon oil Substances 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000019423 pullulan Nutrition 0.000 description 1
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 1
- 229940085605 saccharin sodium Drugs 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 235000019615 sensations Nutrition 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229940037001 sodium edetate Drugs 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229940013618 stevioside Drugs 0.000 description 1
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 description 1
- 235000019202 steviosides Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 235000019408 sucralose Nutrition 0.000 description 1
- 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 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Images
Classifications
-
- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Zoology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
본 발명은 에틸 셀룰로오스 용액으로 습식조립하여 표면개질된 당 또는 당알코올 과립을 주부형제로 포함하는 구강붕해정에 관한 것으로, 당 또는 당알코올을 에틸 셀룰로오스 용액으로 표면개질한 과립형태의 주부형제를 적용함으로써 저압 타정으로도 높은 경도를 얻을 수 있고 타정장애없이 실생산 적용이 가능하며, 약제의 제조, 운반, 보관, 분포, 조제 작업시 취급 중에도 무너지지 않고, 고습도 조건하에서 장기간 저장하여도 경도의 저하 및 붕해의 지연을 억제할 수 있는 우수한 구강붕해정을 얻을 수 있다.The present invention relates to an oral disintegrating tablet comprising as a house excipient sugar or sugar alcohol granules that have been wet-assembled with an ethyl cellulose solution and surface-modified, and a granular main excipient in which sugar or sugar alcohol is surface-modified with an ethyl cellulose solution is applied. As a result, high hardness can be obtained even with low pressure tableting, and practical production application is possible without tableting obstacles, it does not collapse during handling during manufacturing, transportation, storage, distribution, and preparation work, and hardness decreases even after long-term storage under high humidity conditions. It is possible to obtain an excellent oral disintegrating tablet capable of suppressing the delay of disintegration.
Description
본 발명은 구강붕해정에 관한 것으로, 특히 당 또는 당 알코올을 에틸 셀룰로오스 용액으로 습식조립하여 표면개질하여 사용함으로써 저압 타정으로도 높은 경도를 얻을 수 있고 타정장애 없이 실생산 적용이 가능하며 장기간 저장하여도 경도의 저하 및 붕해의 지연을 억제할 수 있는 구강붕해정에 관한 것이다.The present invention relates to an orally disintegrating tablet, in particular, by wet-assembling sugar or sugar alcohol with an ethyl cellulose solution and using it by surface modification, high hardness can be obtained even with low pressure tableting, and practical production application without tableting disorders is possible, and long-term storage It also relates to an oral disintegrating tablet capable of suppressing a decrease in hardness and a delay in disintegration.
약물을 체내에 공급하기 위한 정제 형태의 제제는 오랜 기간 동안 편리하고 유용하게 사용되어 왔다.Formulations in the form of tablets for supplying drugs to the body have been conveniently and usefully used for a long time.
그러나 많은 비율의 사람들이 정제를 삼키는 것에 대한 두려움을 가지고 있고, 손떨림과 연하장애를 갖는 노인, 알약을 삼킬 수 없어서 시럽의 형태로 먹이거나 정제를 갈아서 물에 개어 먹어야 하는 유소아, 여행 등 물을 얻기 어려운 경우, 신장병 환자와 같은 수분섭취 제한환자, 지속적으로 누워 있어서 약물을 복용하기 위해 일어나 앉기 어려운 환자 등에게 정제는 여전히 불편한 제형이다. However, a large percentage of people are afraid of swallowing tablets, elderly people with tremors and swallowing difficulties, infants who cannot swallow pills and have to feed them in the form of syrup or change tablets and eat water, travel, etc. In difficult cases, tablets are still an uncomfortable formulation for patients with limited water intake, such as kidney disease patients, and patients who are constantly lying down and have difficulty sitting up to take drugs.
이러한 불편함을 개선하기 위하여 개발된 것이 구강붕해정(Orally Disintegrating Tablet)이다. 구강붕해정은 구강 내에서 타액에 의하여 수초 내지 수십초 이내에 정제가 붕해되어 물 없이도 복용이 가능하도록 한 정제의 형태이다. 구강붕해정은 속붕정(Fast Disintegrating Tablet), 신속 용융정 (Rapidly Melting Tablet), 구강내 확산정(Orodispersible Tablet), 속용정(Fast Dissolving Tablet), 신속 붕괴정(Rapidly Eroding Tablet) 등 다양한 이름으로 불린다. Orally Disintegrating Tablet was developed to improve such discomfort. Oral disintegrating tablets are in the form of tablets in which the tablets are disintegrated within a few seconds to tens of seconds by saliva in the oral cavity and can be taken without water. Oral disintegrating tablets are under various names such as Fast Disintegrating Tablet, Rapidly Melting Tablet, Orodispersible Tablet, Fast Dissolving Tablet, and Rapidly Eroding Tablet. Is called.
이러한 구강붕해정의 주(主)부형제로 당, 당알코올 등이 사용되고 있다. 그러나, 당 또는 당알코올은 타정성이 좋지 않아 이를 주부형제로 사용하는 경우 결정 셀룰로오스와 같은 기능성 부형제를 혼합하거나 활택제의 양을 증가하는 등의 방법으로 타정성을 높이고자 하고 있다.Sugar, sugar alcohol, etc. are used as the main excipients of these oral disintegrating tablets. However, sugars or sugar alcohols have poor tabletting properties, so when they are used as a home excipient, they are trying to increase tabletting properties by mixing functional excipients such as crystalline cellulose or increasing the amount of a lubricant.
그러나 이러한 경우, 구강붕해정을 투여하였을 때 식감이 나쁘고 이물감이 느껴지며 붕해시간이 길어지는 문제점이 있다.However, in this case, when the oral disintegrating tablet is administered, the texture is bad, a foreign body sensation is felt, and the disintegration time is prolonged.
상기 문제점을 해결하기 위하여, 본 발명은 당 또는 당 알코올을 에틸 셀룰로오스 용액으로 습식조립하여 표면개질하여 구강붕해정에 적용함으로써 저압 타정으로도 높은 경도를 얻을 수 있고 타정장애없이 실생산 적용이 가능하며, 약제의 제조, 운반, 보관, 분포, 조제 작업시 취급 중에도 무너지지 않고, 고습도 조건하에서 장기간 저장하여도 경도의 저하 및 붕해의 지연을 억제할 수 있는 구강붕해정을 제공하는 것을 목적으로 한다.In order to solve the above problem, the present invention can obtain high hardness even with low pressure tableting by wet-assembling sugar or sugar alcohol with ethyl cellulose solution and applying the surface to the oral disintegrating tablet, and it is possible to obtain a high hardness even with tableting difficulties and can be applied to actual production. It is intended to provide an oral disintegrating tablet that does not collapse during handling during manufacturing, transport, storage, distribution, and preparation of drugs, and can suppress the decrease in hardness and delay of disintegration even when stored for a long time under high humidity conditions.
상기 목적을 달성하기 위하여, 본 발명에서는, In order to achieve the above object, in the present invention,
에틸 셀룰로오스 용액으로 습식조립하여 표면개질된 당 또는 당알코올 과립을 주부형제로 포함하는 구강붕해정을 제공한다.It provides an oral disintegrating tablet containing as a house excipient sugar or sugar alcohol granules that are wet-assembled with ethyl cellulose solution and surface-modified.
상기 구강붕해정에서, 상기 당은 글루코스, 말토오스, 덱스트로스, 락토오스, 트레할로스 및 백당 중에서 선택된 1종 이상인 것이 바람직하다.In the oral disintegrating tablet, the sugar is preferably at least one selected from glucose, maltose, dextrose, lactose, trehalose and sucrose.
상기 구강붕해정에서, 상기 당알코올은 만니톨, 솔비톨, 자일리톨, 에리스티톨, 말티톨 및 락티톨 중에서 선택된 1종 이상인 것이 바람직하다.In the oral disintegrating tablet, the sugar alcohol is preferably at least one selected from mannitol, sorbitol, xylitol, erystitol, maltitol, and lactitol.
상기 구강붕해정에서, 상기 에틸 셀룰로오스는 6~55 cps의 점도를 가지는 것이 바람직하다.In the oral disintegrating tablet, the ethyl cellulose preferably has a viscosity of 6 ~ 55 cps.
상기 구강붕해정에서, 상기 당 또는 당알코올 과립은 당 또는 당알코올과 에틸 셀룰로오스 용액을 고형분 기준으로 10:1~80:1의 중량비로 혼합하여 조립되는 것이 바람직하다.In the oral disintegrating tablet, the sugar or sugar alcohol granules are preferably granulated by mixing sugar or sugar alcohol and ethyl cellulose solution in a weight ratio of 10:1 to 80:1 based on solid content.
상기 구강붕해정에서, 상기 에틸 셀룰로오스로 개질된 당 또는 당알코올은 구강붕해정 총중량에 대하여 35~80중량% 함유되는 것이 바람직하다.In the oral disintegrating tablet, the sugar or sugar alcohol modified with ethyl cellulose is preferably contained in an amount of 35 to 80% by weight based on the total weight of the oral disintegrating tablet.
상기 구강붕해정에서, 상기 에틸 셀룰로오스로 개질된 당 또는 당알코올은 구강붕해정 총중량에 대하여 60~80중량% 함유되는 것이 바람직하다.In the oral disintegrating tablet, the sugar or sugar alcohol modified with ethyl cellulose is preferably contained in an amount of 60 to 80% by weight based on the total weight of the oral disintegrating tablet.
상기 구강붕해정은 붕해제를 더 포함할 수 있다.The oral disintegrating tablet may further include a disintegrant.
상기 구강붕해정에서, 상기 붕해제는 크로스포비돈, 크로스카르멜로스 나트륨, 히드록시 프로필 전분 및 전분글리콜산나트륨 중에서 선택된 1종 이상인 것이 바람직하다.In the oral disintegrating tablet, the disintegrant is preferably at least one selected from crospovidone, croscarmellose sodium, hydroxypropyl starch, and sodium starch glycolate.
상기 구강붕해정에서, 상기 에틸 셀룰로오스 용액은 에탄올에 에틸 셀룰로오스를 분산시킨 것임이 바람직하다.In the oral disintegrating tablet, the ethyl cellulose solution is preferably one obtained by dispersing ethyl cellulose in ethanol.
상기 구강붕해정에서, 상기 습식조립은 유동층 조립법을 사용하는 것이 바람직하다.In the oral disintegrating tablet, it is preferable to use a fluidized bed granulation method for the wet assembly.
상기 구강붕해정에서, 상기 유동층 조립법에서 유동화제로는 경질 무수규산을 사용하는 것이 바람직하다.In the oral disintegrating tablet, it is preferable to use hard silicic anhydride as a fluidizing agent in the fluidized bed granulation method.
상기 구강붕해정에서, 상기 유동화제는 주부형제 고형분의 총중량에 대하여 0.1~1.0중량% 사용하는 것이 바람직하다. In the oral disintegrating tablet, the fluidizing agent is preferably used in an amount of 0.1 to 1.0% by weight based on the total weight of the solid content of the main excipient.
본 발명의 당 또는 당알코올을 에틸 셀룰로오스 용액으로 표면개질한 과립형태의 주부형제는 에틸 셀룰로오스가 정제의 골격을 유지하여 타정성이 우수하고 구강 내 투여시에는 수로역할을 하여 신속한 붕해를 방해하지 않는다. 이러한 주부형제를 구강붕해정에 적용함으로써 저압 타정으로도 높은 경도를 얻을 수 있고 타정장애없이 실생산 적용이 가능하며, 약제의 제조, 운반, 보관, 분포, 조제 작업시 취급 중에도 무너지지 않고, 고습도 조건하에서 장기간 저장하여도 경도의 저하 및 붕해의 지연을 억제할 수 있다.In the granular form of house-carrying agent in which the sugar or sugar alcohol of the present invention is surface-modified with ethyl cellulose solution, ethyl cellulose maintains the skeleton of the tablet, so it has excellent tabletting properties, and does not interfere with rapid disintegration by acting as a water channel when administered orally. . By applying such a housewife to oral disintegrating tablets, high hardness can be obtained even with low-pressure tableting, and practical production application is possible without tableting difficulties, and does not collapse during handling during manufacturing, transportation, storage, distribution, and preparation of drugs, and under high humidity conditions. Even if it is stored for a long time under the condition, the decrease in hardness and delay in disintegration can be suppressed.
도 1은 실시예 5와 비교예 6의 시료에 대하여 타정압에 따른 경도를 확인한 결과를 나타낸 그래프이다.1 is a graph showing a result of confirming the hardness according to the tableting pressure for samples of Example 5 and Comparative Example 6.
본 발명의 구강붕해정은 에틸 셀룰로오스 용액으로 습식조립하여 표면개질된 당 또는 당알코올 과립을 주부형제로 사용하는 것을 특징으로 한다.The oral disintegrating tablet of the present invention is characterized in that the surface-modified sugar or sugar alcohol granules are wet-assembled with an ethyl cellulose solution as a main excipient.
에틸 셀룰로오스 용액으로 습식조립하여 표면개질된 당 또는 당알코올 과립은 다음과 같이 제조한다.Sugar or sugar alcohol granules that are surface-modified by wet assembly with an ethyl cellulose solution are prepared as follows.
당으로는 글루코스, 말토오스, 덱스트로스, 락토오스, 트레할로스, 백당 등을 사용할 수 있고, 당알코올로는 만니톨, 솔비톨, 자일리톨, 에리스티톨, 말티톨, 락티톨 등을 사용할 수 있다. 만니톨을 사용하는 것이 보다 바람직하다. Glucose, maltose, dextrose, lactose, trehalose, sucrose, and the like can be used as sugar, and mannitol, sorbitol, xylitol, erystitol, maltitol, lactitol, and the like can be used as sugar alcohol. It is more preferable to use mannitol.
당 또는 당알코올을 습식조립하기 위한 물질로는 에틸 셀룰로오스 용액을 사용한다. 에틸 셀룰로오스 용액의 용매로는 에탄올을 사용하는 것이 바람직하며, 75% 에탄올을 사용하는 것이 특히 바람직하다. 에탄올에 에틸 셀룰로오스를 분산시켜 에틸 셀룰로오스 용액을 제조한다.Ethyl cellulose solution is used as a material for wet-assembly of sugar or sugar alcohol. Ethanol is preferably used as a solvent for the ethyl cellulose solution, and 75% ethanol is particularly preferably used. Ethyl cellulose is dispersed in ethanol to prepare an ethyl cellulose solution.
에틸 셀룰로오스는 6~55 cps의 점도를 가진 것을 사용하는 것이 바람직하다. 가장 바람직하게는, 6~11 cps의 점도를 가지는 것을 사용할 수 있는데, 그 이유는 6~11 cps 점도를 가지는 에틸셀룰로오스로 습식 조립할 때 바람직한 과립 사이즈가 제조되어 붕해시간을 단축 시킬 수 있다. It is preferable to use ethyl cellulose having a viscosity of 6 to 55 cps. Most preferably, those having a viscosity of 6 to 11 cps may be used, because when wet granulation is performed with ethyl cellulose having a viscosity of 6 to 11 cps, a desirable granule size is prepared, and the disintegration time can be shortened.
당 또는 당알코올을 에틸 셀룰로오스 용액으로 습식조립하여 당 또는 당알코올의 표면을 개질하여 과립화한다.Sugar or sugar alcohol is wet-assembled with ethyl cellulose solution, and the surface of sugar or sugar alcohol is modified and granulated.
이때 당 또는 당알코올과 에틸 셀룰로오스 용액은 고형분을 기준으로 10:1~80:1의 중량비로 혼합하는 것이 바람직하다. 20:1~30:1의 중량비로 혼합하는 것이 보다 바람직하다.At this time, it is preferable to mix the sugar or sugar alcohol and ethyl cellulose solution in a weight ratio of 10:1 to 80:1 based on the solid content. It is more preferable to mix in a weight ratio of 20:1 to 30:1.
조립방법으로는 습식조립법을 사용하는 것이 바람직한데, 습식조립법을 사용하면 건식조립법을 사용하는 경우에 비해 균일한 입자지름을 얻을 수 있어 미분의 비율이 감소하고 일반적으로 성형성이 좋은 과립이 얻어지기 때문이다.As for the granulation method, it is preferable to use the wet granulation method, but when the wet granulation method is used, a uniform particle diameter can be obtained compared to the case of using the dry granulation method, so that the proportion of fines decreases and generally, granules with good moldability are obtained. Because.
습식조립법으로는 유동층 조립법, 교반 조립법, 원통압출 조립법, 전동 유동층 조립 코팅법, 분무건조법 등 통상적인 습식조립법을 사용할 수 있으며, 유동층 조립기를 사용한 유동층 조립법을 사용하는 것이 보다 바람직하다. As the wet assembly method, conventional wet assembly methods such as a fluidized bed granulation method, agitation granulation method, a cylindrical extrusion granulation method, an electric fluidized bed granulation coating method, and a spray drying method can be used, and it is more preferable to use a fluidized bed granulation method using a fluidized bed granulator.
유동층 조립법은 의약성분 및 의약품 부형제의 혼합물을 유동상태로 유지하고, 결합제 등을 포함한 용액 또는 현탁액을 분무하여, 혼합물끼리 그 결합제에 의해 응집 조립시키는 방법이다. The fluidized bed granulation method is a method in which a mixture of pharmaceutical ingredients and pharmaceutical excipients is kept in a fluid state, a solution or suspension containing a binder, etc. is sprayed, and the mixtures are coagulated and granulated by the binder.
유동층 조립법에 의하여 주부형제를 조립할 때는 유동화제를 사용하며, 유동화제로는 경질 무수규산을 사용하는 것이 보다 바람직하다. 유동화제는 주부형제 고형분의 총중량에 대하여 0.1~1.0중량% 사용하는 것이 바람직하다.A fluidizing agent is used when granulating the house-buying agent by the fluidized bed granulation method, and it is more preferable to use light anhydrous silicic acid as the fluidizing agent. The fluidizing agent is preferably used in an amount of 0.1 to 1.0% by weight based on the total weight of the solid content of the main excipient.
주부형제를 조립할 때는 감미제, 붕해제, 착색제, 결합제 등 통상의 첨가제를 첨가할 수 있다.When assembling the house-buying agent, conventional additives, such as a sweetening agent, a disintegrant, a coloring agent, and a binder, may be added.
표면개질된 과립형태의 주부형제는 에틸 셀룰로오스가 정제의 골격을 유지하여 타정성이 우수하고 구강 내 투여시에는 수로역할을 하여 신속한 붕해를 방해하지 않는다.The surface-modified granular form of the house excipient is excellent in tabletting ability because ethyl cellulose maintains the skeleton of the tablet, and does not interfere with rapid disintegration by acting as a water channel when administered orally.
상기 주부형제를 사용하여 구강붕해정을 제조한다. Oral disintegrating tablets are prepared using the housewife.
구강붕해정은 상기 주부형제를 사용하는 것을 제외하고는 통상적인 방법에 의하여 제조한다.Oral disintegrating tablets are prepared by a conventional method except for the use of the above-mentioned housewife.
주부형제인 에틸 셀룰로오스로 개질된 당 또는 당알코올은 구강붕해정 총중량에 대하여 35~80중량% 함유되는 것이 바람직하고, 45~80중량% 함유되는 것이 보다 바람직하며, 60~80중량% 함유되는 것이 가장 바람직하다.The sugar or sugar alcohol modified with ethyl cellulose as a main excipient is preferably contained in 35 to 80% by weight, more preferably 45 to 80% by weight, and 60 to 80% by weight based on the total weight of the oral disintegrating tablet. Most preferred.
본 발명의 구강붕해정은 에틸 셀룰로오스로 개질된 당 또는 당알코올을 주부형제로 사용하고, 붕해제를 포함한다.The oral disintegrating tablet of the present invention uses a sugar or sugar alcohol modified with ethyl cellulose as a housewife, and contains a disintegrant.
붕해제로는 크로스포비돈, 크로스카르멜로스 나트륨, 히드록시 프로필 전분, 전분글리콜산나트륨 등을 사용할 수 있다. 붕해제는 구강붕해정 총중량에 대하여 6~25중량% 함유되는 것이 바람직하고, 7~20 중량% 함유되는 것이 보다 바람직하며, 8~15중량% 함유되는 것이 가장 바람직하다.As the disintegrant, crospovidone, croscarmellose sodium, hydroxypropyl starch, sodium starch glycolate, and the like can be used. The disintegrant is preferably contained in 6 to 25% by weight based on the total weight of the oral disintegrating tablet, more preferably contained in 7 to 20% by weight, and most preferably contained in 8 to 15% by weight.
본 발명의 구강붕해정은 결합제, 활택제, 감미제, 부(副)부형제, 계면활성제, 산미료, 발포제, 안정화제, 착향제(향료), 착색제, 방부제, pH 조절제 등을 정제의 붕해성을 손상하지 않는 범위에서 추가로 포함할 수 있다.The oral disintegrating tablet of the present invention impairs the disintegration properties of the tablet by using a binder, a lubricant, a sweetener, an auxiliary excipient, a surfactant, an acidulant, a foaming agent, a stabilizer, a flavoring agent (fragrance), a colorant, a preservative, and a pH adjuster. It may additionally be included in the range that does not.
결합제로는 하이드록시프로필셀룰로즈, 알긴산, 젤라틴, 부분 알파화(α화) 전분, 포비돈, 아라비아검, 풀루란, 덱스트린 등을 사용할 수 있다. 결합제로는 부분 알파화전분을 사용하는 것이 보다 바람직한데, 부분 알파화 전분은 결합제로서 충분한 효과를 발휘해 양호한 조립성을 보여 정제 경도를 지지하면서, 정제의 붕해성을 방해하지 않기 때문이다. As the binder, hydroxypropylcellulose, alginic acid, gelatin, partially alpha-gelatinized (α) starch, povidone, gum arabic, pullulan, dextrin, and the like can be used. It is more preferable to use partially-gelatinized starch as the binder, because partially-gelatinized starch exhibits a sufficient effect as a binder, shows good granularity, supports tablet hardness, and does not interfere with the disintegration property of the tablet.
활택제로는 스테아르산, 스테아르산 마그네슘, 스테아르산 칼슘, 자당 지방산 에스테르, 폴리에틸렌글리콜, 푸마르산 스테아릴 나트륨, 콜로이드성 이산화규소, 탈크, 글리세릴 베헤네이트, 메타규산 알루민산 마그네슘 등을 사용할 수 있다. 그 중 스테아르산 마그네슘을 사용하는 것이 보다 바람직한데, 소량의 첨가로 충분한 활택효과를 얻을 수 있기 때문이다. As the lubricant, stearic acid, magnesium stearate, calcium stearate, sucrose fatty acid ester, polyethylene glycol, sodium stearyl fumarate, colloidal silicon dioxide, talc, glyceryl behenate, magnesium metasilicate aluminate, and the like can be used. Among them, it is more preferable to use magnesium stearate, because a sufficient lubricating effect can be obtained by adding a small amount.
감미제로는 사카린 나트륨, 디포타슘글리시리제이트, 아스파탐, 스테비어, 소마틴, 수크랄로스, 스테비오사이드, 네오헤스피리딘, 알리탐, 아세설팜 칼륨 등을 사용할 수 있다.As the sweetening agent, saccharin sodium, dipotassium glycyrrhizate, aspartame, stevia, somartin, sucralose, stevioside, neohespirin, alitam, acesulfame potassium, and the like can be used.
부부형제로는 개질되지 않은 당이나 당알코올, 미결정질 셀룰로오스, 옥수수전분, 전분가수분해물(덱스트린, 말토덱스트린 등), 카르복시메틸셀룰로오스칼슘, 경화유, 탈크 등을 사용할 수 있다. Unmodified sugar or sugar alcohol, microcrystalline cellulose, corn starch, starch hydrolyzate (dextrin, maltodextrin, etc.), carboxymethyl cellulose calcium, hydrogenated oil, talc, and the like can be used as the couple brother.
계면활성제로는 폴리옥시에틸렌 경화 피마자유, 폴리옥시에틸렌폴리옥시프로필렌글리콜, 소르비탐지방산에스테르, 폴리솔베이트, 지방산글리세린에스테르, 라우릴황산나트륨 등을 사용할 수 있다. As the surfactant, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene glycol, sorbitam fatty acid ester, polysorbate, fatty acid glycerin ester, sodium lauryl sulfate, and the like can be used.
산미료로는 시트르산, 주석산, 말산, 아스코르브산 등을 사용할 수 있다.Citric acid, tartaric acid, malic acid, ascorbic acid, and the like can be used as the acidulant.
발포제로는 탄산수소나트륨, 탄산나트륨 등을 사용할 수 있다.Sodium hydrogen carbonate, sodium carbonate, etc. can be used as the blowing agent.
안정화제로는 에데트산나트륨, 토코페롤, 시클로덱스트린 등을 사용할 수 있다.As a stabilizer, sodium edetate, tocopherol, cyclodextrin, and the like can be used.
착향제(향료)로는 레몬유, 오렌지유, 멘톨 등을 사용할 수 있다.Lemon oil, orange oil, menthol, etc. can be used as the flavoring agent (scent).
착색제로는 식용적색 2호, 식용청색 2호, 식용황색 5호, 식용레이크색소, 삼이산화철 등을 사용할 수 있다. As a coloring agent, food red No. 2, food blue No. 2, food yellow No. 5, edible lake color, iron trioxide, etc. can be used.
방부제로는 벤조산나트륨, 파라옥시안식향산메틸, 파라옥시안식향산프로필 등을 사용할 수 있다.As the preservative, sodium benzoate, methyl paraoxybenzoate, propyl paraoxybenzoate, and the like can be used.
pH 조절제로는 구연산, 인산수소칼슘, 탄산수소나트륨 등을 사용할 수 있다.As the pH adjuster, citric acid, calcium hydrogen phosphate, sodium hydrogen carbonate, or the like can be used.
혼합방법으로는 혼합, 연합, 조립 등 통상적으로 사용되는 방법을 사용한다. 예를 들면, 버티컬 그래뉼레이터 VG10[파우레크 사제], 만능 연합기(밭철공소제), 유동층 조립기 LAB-1, FD-3S[파우레크 사제], 전동유동형 코팅 조립기 MP-10, MP-400[파우레크 사제] 등의 장치를 사용하여 혼합할 수 있다.As the mixing method, commonly used methods such as mixing, coalescence, and granulation are used. For example, vertical granulator VG10 [manufactured by Paurek], universal combiner (manufactured by field ironworks), fluid bed granulator LAB-1, FD-3S [manufactured by Paurek], electric flow type coating granulator MP-10, MP-400[ It can be mixed using a device such as [manufactured by Paurec Corporation].
조립방법으로는 공지된 방법인 습식조립법과 건식조립법을 사용할 수 있다. 습식조립법의 경우, 유동층 조립법, 교반 조립법, 원통압출 조립법, 전동 유동층 조립 코팅법, 분무건조법 등 통상적인 습식조립법을 사용할 수 있다. 건식조립법의 경우, 롤러 컴팩터 등의 건식 조립기, 슬러그 타정기 등 통상적인 건식조립 장치를 이용하여 조립할 수 있다. As the assembly method, known methods of wet assembly and dry assembly may be used. In the case of the wet assembly method, a conventional wet assembly method such as a fluidized bed granulation method, a stirring granulation method, a cylindrical extrusion granulation method, an electric fluidized bed granulation coating method, and a spray drying method can be used. In the case of the dry assembly method, it can be assembled using a dry granulator such as a roller compactor or a conventional dry assembly device such as a slug tablet press.
건조방법으로는 진공 건조, 유동층 건조 등 정제의 제조에 통상적으로 사용되는 건조방법을 사용한다.As a drying method, a drying method commonly used in the manufacture of tablets, such as vacuum drying and fluidized bed drying, is used.
타정은 단발 정제기(키쿠스이 제작소제), 로터리식 정제 프레스기(키쿠스이 제작소제) 등을 이용하여 타정하는 것이 바람직하며, 3.0~30.0 kN/cm2, 바람직하게는 6.0~12.0 kN/cm2의 압력으로 타정하는 것이 바람직하다.Tableting is preferably performed using a single-shot tablet press (manufactured by Kikusui), a rotary tablet press (manufactured by Kikusui), etc., and 3.0 to 30.0 kN/cm 2 , preferably 6.0 to 12.0 kN/cm 2 It is preferable to tablet with pressure.
이하 실시예를 통하여 본 발명을 보다 상세하게 설명한다. 하기 실시예는 본 발명을 예시하는 것으로 본 발명의 범위가 이에 한정되는 것은 아니다.The present invention will be described in more detail through the following examples. The following examples illustrate the present invention, and the scope of the present invention is not limited thereto.
<제조예 1><Production Example 1>
D-만니톨 66.3g과 경질무수규산 0.35g을 유동층 조립기(Freund-Vector VFC-LAB Micro)에 투입하고, 에틸 셀룰로오스(7cps) 3.33g을 75% 에탄올 111.0g에 분산시킨 액으로 과립화한 후 건조하여 과립물을 제조하였다. 66.3 g of D-mannitol and 0.35 g of light anhydrous silicic acid were added to a fluidized bed granulator (Freund-Vector VFC-LAB Micro), and 3.33 g of ethyl cellulose (7 cps) was granulated with a solution dispersed in 111.0 g of 75% ethanol and dried. Thus, granules were prepared.
<제조예 2><Production Example 2>
D-만니톨 66.3g과 경질무수규산 0.35g을 유동층 조립기기(Freund-Vector VFC-LAB Micro)에 투입하고, 에틸 셀룰로오스(10cps) 3.33g을 75% 에탄올 111.0g에 분산시킨 액으로 과립화한 후 건조하여 과립물을 제조하였다.66.3 g of D-mannitol and 0.35 g of light anhydrous silicic acid were added to a fluidized bed assembly machine (Freund-Vector VFC-LAB Micro), and 3.33 g of ethyl cellulose (10 cps) was granulated into a solution dispersed in 111.0 g of 75% ethanol. Dry to prepare granules.
<제조예 3><Production Example 3>
D-만니톨 66.3g과 경질무수규산 0.35g을 유동층 조립기기(Freund-Vector VFC-LAB Micro)에 투입하고, 에틸 셀룰로오스(50cps) 3.33g을 75% 에탄올 111.0g에 분산시킨 액으로 과립화한 후 건조하여 과립물을 제조하였다. 66.3 g of D-mannitol and 0.35 g of light anhydrous silicic acid were added to a fluidized bed assembly machine (Freund-Vector VFC-LAB Micro), and 3.33 g of ethyl cellulose (50 cps) was granulated into a solution dispersed in 111.0 g of 75% ethanol. Dry to prepare granules.
<제조예 4><Production Example 4>
D-만니톨 67.4g과 경질무수규산 0.35g을 유동층 조립기(Freund-Vector VFC-LAB Micro)에 투입하고, 에틸 셀룰로오스(7cps) 2.26g을 75% 에탄올 75.4g에 분산시킨 액으로 과립화한 후 건조하여 과립물을 제조하였다. 67.4 g of D-mannitol and 0.35 g of light anhydrous silicic acid were added to a fluidized bed granulator (Freund-Vector VFC-LAB Micro), and 2.26 g of ethyl cellulose (7 cps) was granulated with a solution dispersed in 75.4 g of 75% ethanol and dried. Thus, granules were prepared.
<실시예 1><Example 1>
상기 제조예 1의 에틸 셀룰로오스(7cps)로 개질한 D-만니톨 56.0g과 옥수수전분 7.0g, 메타규산알루민산마그네슘 1.8g을 유동층 조립기에 투입하여 혼합한 후, PC-10 2.1g을 정제수 70.0g에 분산시킨 분산액으로 과립화한 후 건조하여 과립물을 제조하였다. 56.0 g of D-mannitol modified with ethyl cellulose (7 cps) of Preparation Example 1, 7.0 g of corn starch, and 1.8 g of magnesium aluminate metasilicate were added to a fluidized bed granulator and mixed, and then 2.1 g of PC-10 was added to 70.0 g of purified water. It was granulated with the dispersion liquid dispersed in and dried to prepare granules.
얻어진 과립물 66.8g에 크로스포비돈 CL-SF 1.9g, 아스파탐 0.7g, 스테아르산마그네슘 0.6g을 더하고 폴리에틸렌 비닐백에서 혼합하여 타정혼합물을 제조하였다. To 66.8 g of the obtained granules, 1.9 g of crospovidone CL-SF, 0.7 g of aspartame, and 0.6 g of magnesium stearate were added and mixed in a polyethylene plastic bag to prepare a tableting mixture.
상기 타정혼합물을 타정압 6~7kN으로 타정하여 직경 7.2mm, 중량 150mg의 정제를 얻었다. The tableting mixture was tableted with a tableting pressure of 6 to 7 kN to obtain tablets having a diameter of 7.2 mm and a weight of 150 mg.
<실시예 2><Example 2>
상기 제조예 1의 에틸 셀룰로오스 (7cps)로 개질한 D-만니톨 47.9g과 옥수수전분 7.0g, 메타규산알루민산마그네슘 1.8g을 유동층 조립기에 투입하여 혼합한 후, PC-10 2.1g 을 정제수 70.0g에 분산시킨 분산액으로 과립화한 후 건조하여 과립물을 제조하였다.After mixing 47.9 g of D-mannitol modified with ethyl cellulose (7 cps) of Preparation Example 1, 7.0 g of corn starch, and 1.8 g of magnesium aluminate metasilicate in a fluidized bed granulator, 2.1 g of PC-10 was added to 70.0 g of purified water. It was granulated with the dispersion liquid dispersed in and dried to prepare granules.
얻어진 과립물 58.8g에 상기 제조예 4에서 개질된 D-만니톨 7.0g, 크로스포비돈 CL-SF 3.3g, 아스파탐 0.7g, 스테아르산마그네슘 0.6g을 더하고 폴리에틸렌 비닐백에서 혼합하여 타정혼합물을 제조하였다.To 58.8 g of the obtained granules, 7.0 g of D-mannitol modified in Preparation Example 4, 3.3 g of crospovidone CL-SF, 0.7 g of aspartame, and 0.6 g of magnesium stearate were added and mixed in a polyethylene plastic bag to prepare a tableting mixture.
상기 타정혼합물을 타정압 6~7kN으로 타정하여 직경 7.2mm, 중량 150mg의 정제를 얻었다. The tableting mixture was tableted with a tableting pressure of 6 to 7 kN to obtain tablets having a diameter of 7.2 mm and a weight of 150 mg.
<실시예 3><Example 3>
상기 제조예 2의 에틸 셀룰로오스 (10cps)로 개질한 D-만니톨 56g과 옥수수전분 7.0g, 메타규산알루민산마그네슘 1.8g을 유동층 조립기에 투입하여 혼합한 후, PC-10 2.1g을 정제수 70.0g에 분산시킨 분산액으로 과립화한 후 건조하여 과립물을 제조하였다.56 g of D-mannitol modified with ethyl cellulose (10 cps) of Preparation Example 2, 7.0 g of corn starch, and 1.8 g of magnesium aluminate metasilicate were added to a fluidized bed granulator and mixed, and then 2.1 g of PC-10 was added to 70.0 g of purified water. After granulating with the dispersed dispersion, it was dried to prepare granules.
얻어진 과립물 66.8g에 크로스포비돈 CL-SF 1.9g, 아스파탐 0.7g, 스테아르산마그네슘 0.6g을 더하고 폴리에틸렌 비닐백에서 혼합하여 타정혼합물을 제조하였다. To 66.8 g of the obtained granules, 1.9 g of crospovidone CL-SF, 0.7 g of aspartame, and 0.6 g of magnesium stearate were added and mixed in a polyethylene plastic bag to prepare a tableting mixture.
상기 타정혼합물을 타정압 6~7kN으로 타정하여 직경 7.2mm, 중량 150mg의 정제를 얻었다. The tableting mixture was tableted with a tableting pressure of 6 to 7 kN to obtain tablets having a diameter of 7.2 mm and a weight of 150 mg.
<실시예 4><Example 4>
상기 제조예 3의 에틸 셀룰로오스 (50cps)로 개질한 D-만니톨 56g과 옥수수전분 7.0g, 메타규산알루민산마그네슘 1.8g을 유동층 조립기에 투입하여 혼합한 후, PC-10 2.1g을 정제수 70.0g에 분산시킨 분산액으로 과립화한 후 건조하여 과립물을 제조하였다. 56 g of D-mannitol modified with ethyl cellulose (50 cps) of Preparation Example 3, 7.0 g of corn starch, and 1.8 g of magnesium aluminate metasilicate were added to a fluidized bed granulator and mixed, and then 2.1 g of PC-10 was added to 70.0 g of purified water. After granulating with the dispersed dispersion, it was dried to prepare granules.
얻어진 과립물 66.8g에 크로스포비돈 CL-SF 1.9g, 아스파탐 0.7g, 스테아르산마그네슘 0.6g을 더하고 폴리에틸렌 비닐백에서 혼합하여 타정혼합물을 제조하였다. To 66.8 g of the obtained granules, 1.9 g of crospovidone CL-SF, 0.7 g of aspartame, and 0.6 g of magnesium stearate were added and mixed in a polyethylene plastic bag to prepare a tableting mixture.
상기 타정혼합물을 타정압 6~7kN으로 타정하여 직경 7.2mm, 중량 150mg의 정제를 얻었다. The tableting mixture was tableted with a tableting pressure of 6 to 7 kN to obtain tablets having a diameter of 7.2 mm and a weight of 150 mg.
<실시예 5><Example 5>
상기 제조예 1의 에틸 셀룰로오스 (7cps)로 개질한 D-만니톨 33.4g과 옥수수전분 4.0g, 메타규산알루민산마그네슘 1.0g을 유동층 조립기에 투입하여 혼합한 후, PC-10 1.2g을 정제수 40.0g에 분산시킨 분산액으로 과립화한 후 건조하여 과립물을 제조하였다. 33.4 g of D-mannitol modified with ethyl cellulose (7 cps) of Preparation Example 1, 4.0 g of corn starch, and 1.0 g of magnesium aluminate metasilicate were added to a fluidized bed granulator and mixed, and then 1.2 g of PC-10 was added to 40.0 g of purified water. It was granulated with the dispersion liquid dispersed in and dried to prepare granules.
얻어진 과립물 39.5g에 디펜히드라민 약물 펠렛 36.9g을 더하고 폴리에틸렌 비닐백에서 혼합한 후, 크로스포비돈 CL-SF 2.1g, 아스파탐 0.9g, 스테아르산마그네슘 0.6g을 더하고 폴리에틸렌 비닐백에서 혼합하여 타정혼합물을 제조하였다. Diphenhydramine drug pellet 36.9 g was added to 39.5 g of the obtained granules and mixed in a polyethylene plastic bag, followed by adding 2.1 g of crospovidone CL-SF, 0.9 g of aspartame, and 0.6 g of magnesium stearate, and mixing in a polyethylene plastic bag. Was prepared.
상기 타정혼합물을 타정압 11~12kN, 15~16kN, 22kN으로 각각 타정하여 직경 9.0mm, 중량 229.2mg의 정제를 얻었다. The tableting mixture was tableted with a tableting pressure of 11 to 12 kN, 15 to 16 kN, and 22 kN, respectively, to obtain tablets having a diameter of 9.0 mm and a weight of 229.2 mg.
<비교예 1><Comparative Example 1>
개질되지 않은 일반 D-만니톨 54.6g와 옥수수전분 7.0g, 메타규산알루민산마그네슘 1.8g을 유동층 조립기에 투입하여 혼합한 후, PC-10 2.1g을 정제수 70.0g에 분산시킨 분산액으로 과립화한 후 건조하여 과립물을 제조하였다. After mixing 54.6 g of unmodified general D-mannitol, 7.0 g of corn starch, and 1.8 g of magnesium aluminate metasilicate into a fluidized bed granulator, 2.1 g of PC-10 was dispersed in 70.0 g of purified water, and then granulated into a dispersion. Dry to prepare granules.
얻어진 과립물 65.4g에 크로스포비돈 CL-SF 3.3g, 아스파탐 0.7g, 스테아르산마그네슘 0.6g을 더하고 폴리에틸렌 비닐백에서 혼합하여 타정혼합물을 제조하였다.To 65.4 g of the obtained granules, 3.3 g of crospovidone CL-SF, 0.7 g of aspartame, and 0.6 g of magnesium stearate were added and mixed in a polyethylene plastic bag to prepare a tableting mixture.
상기 타정혼합물을 타정압 6~7kN으로 타정하여 직경 7.2mm, 중량 150mg의 정제를 얻었다.The tableting mixture was tableted with a tableting pressure of 6 to 7 kN to obtain tablets having a diameter of 7.2 mm and a weight of 150 mg.
<비교예 2><Comparative Example 2>
개질되지 않은 일반 D-만니톨 54.6g와 옥수수전분 7.0g, 메타규산알루민산마그네슘 1.8g을 유동층 조립기에 투입하여 혼합한 후, PC-10 2.1g을 정제수 70.0g에 분산시킨 분산액으로 과립화한 후 건조하여 과립물을 제조했다. After mixing 54.6 g of unmodified general D-mannitol, 7.0 g of corn starch, and 1.8 g of magnesium aluminate metasilicate into a fluidized bed granulator, 2.1 g of PC-10 was dispersed in 70.0 g of purified water, and then granulated into a dispersion. It was dried to prepare granules.
얻어진 과립물 65.4g에 크로스포비돈 CL-SF 1.9g, 에틸 셀룰로오스(7cps) 분말 1.4g, 아스파탐 0.7g, 스테아르산마그네슘 0.6g을 더하고 폴리에틸렌 비닐백에서 혼합하여 타정혼합물을 제조하였다. To 65.4 g of the obtained granules, 1.9 g of crospovidone CL-SF, 1.4 g of ethyl cellulose (7 cps) powder, 0.7 g of aspartame, and 0.6 g of magnesium stearate were added and mixed in a polyethylene plastic bag to prepare a tableting mixture.
상기 타정혼합물을 타정압 6~7kN으로 타정하여 직경 7.2mm, 중량 150mg의 정제를 얻었다. The tableting mixture was tableted with a tableting pressure of 6 to 7 kN to obtain tablets having a diameter of 7.2 mm and a weight of 150 mg.
<비교예 3><Comparative Example 3>
개질되지 않은 일반 D-만니톨 54.6g와 에틸 셀룰로오스(7cps) 분말 1.4g, 옥수수전분 7.0g, 메타규산알루민산마그네슘 1.8g을 유동층 조립기에 투입하여 혼합한 후, PC-10 2.1g을 정제수 70.0g에 분산시킨 분산액으로 과립화한 후 건조하여 과립물을 제조하였다.54.6 g of unmodified general D-mannitol, 1.4 g of ethyl cellulose (7 cps) powder, 7.0 g of corn starch, and 1.8 g of magnesium metasilicate aluminate were added to the fluidized bed granulator and mixed, and 2.1 g of PC-10 was added to 70.0 g of purified water. It was granulated with the dispersion liquid dispersed in and dried to prepare granules.
얻어진 과립물 66.8g에 크로스포비돈 CL-SF 1.9g, 아스파탐 0.7g, 스테아르산마그네슘 0.6g을 더하고 폴리에틸렌 비닐백에서 혼합하여 타정혼합물을 제조하였다. To 66.8 g of the obtained granules, 1.9 g of crospovidone CL-SF, 0.7 g of aspartame, and 0.6 g of magnesium stearate were added and mixed in a polyethylene plastic bag to prepare a tableting mixture.
상기 타정혼합물을 타정압 6~7kN으로 타정하여 직경 7.2mm, 중량 150mg의 정제를 얻었다. The tableting mixture was tableted with a tableting pressure of 6 to 7 kN to obtain tablets having a diameter of 7.2 mm and a weight of 150 mg.
<비교예 4><Comparative Example 4>
개질되지 않은 일반 D-만니톨 54.6g와 에틸 셀룰로오스(10cps) 분말 1.4g, 옥수수전분 7.0g, 메타규산알루민산마그네슘 1.8g을 유동층 조립기에 투입하여 혼합한 후, PC-10 2.1g을 정제수 70.0g에 분산시킨 분산액으로 과립화한 후 건조하여 과립물을 제조하였다. 54.6 g of unmodified general D-mannitol, 1.4 g of ethyl cellulose (10 cps) powder, 7.0 g of corn starch, and 1.8 g of magnesium aluminate metasilicate were added to the fluidized bed granulator and mixed, and 2.1 g of PC-10 was added to 70.0 g of purified water. It was granulated with the dispersion liquid dispersed in and dried to prepare granules.
얻어진 과립물 66.8g에 크로스포비돈 CL-SF 1.9g, 아스파탐 0.7g, 스테아르산마그네슘 0.6g을 더하고 폴리에틸렌 비닐백에서 혼합하여 타정혼합물을 제조하였다. To 66.8 g of the obtained granules, 1.9 g of crospovidone CL-SF, 0.7 g of aspartame, and 0.6 g of magnesium stearate were added and mixed in a polyethylene plastic bag to prepare a tableting mixture.
상기 타정혼합물을 타정압 6~7kN으로 타정하여 직경 7.2mm, 중량 150mg의 정제를 얻었다. The tableting mixture was tableted with a tableting pressure of 6 to 7 kN to obtain tablets having a diameter of 7.2 mm and a weight of 150 mg.
<비교예 5><Comparative Example 5>
개질되지 않은 일반 D-만니톨 54.6g와 에틸 셀룰로오스(50cps) 분말 1.4g, 옥수수전분 7.0g, 메타규산알루민산마그네슘 1.8g을 유동층 조립기에 투입하여 혼합한 후, PC-10 2.1g을 정제수 70.0g에 분산시킨 분산액으로 과립화한 후 건조하여 과립물을 제조하였다. 54.6 g of unmodified general D-mannitol, 1.4 g of ethyl cellulose (50 cps) powder, 7.0 g of corn starch, and 1.8 g of magnesium metasilicate aluminate were added to the fluidized bed granulator and mixed, and 2.1 g of PC-10 was added to 70.0 g of purified water. It was granulated with the dispersion liquid dispersed in and dried to prepare granules.
얻어진 과립물 66.8g에 크로스포비돈 CL-SF 1.9g, 아스파탐 0.7g, 스테아르산마그네슘 0.6g을 더하고 폴리에틸렌 비닐백에서 혼합하여 타정혼합물을 제조하였다. To 66.8 g of the obtained granules, 1.9 g of crospovidone CL-SF, 0.7 g of aspartame, and 0.6 g of magnesium stearate were added and mixed in a polyethylene plastic bag to prepare a tableting mixture.
상기 타정혼합물을 타정압 6~7kN으로 타정하여 직경 7.2mm, 중량 150mg의 정제를 얻었다.The tableting mixture was tableted with a tableting pressure of 6 to 7 kN to obtain tablets having a diameter of 7.2 mm and a weight of 150 mg.
<비교예 6><Comparative Example 6>
개질되지 않은 일반 D-만니톨 32.3g와 에틸 셀룰로오스(7cps) 분말 1.1g, 옥수수전분 4.0g, 메타규산알루민산마그네슘 1.0g을 유동층 조립기에 투입하여 혼합한 후, PC-10 1.2g을 정제수 40.0g에 분산시킨 분산액으로 과립화한 후 건조하여 과립물을 제조하였다.32.3 g of unmodified general D-mannitol, 1.1 g of ethyl cellulose (7 cps) powder, 4.0 g of corn starch, and 1.0 g of magnesium metasilicate aluminate were added to the fluidized bed granulator and mixed, and then 1.2 g of PC-10 was added to 40.0 g of purified water. It was granulated with the dispersion liquid dispersed in and dried to prepare granules.
얻어진 과립물 39.5g에 디펜히드라민 약물 펠렛 36.9g을 폴리에틸렌 비닐백에서 혼합한 후, 크로스포비돈 CL-SF 2.1g, 아스파탐 0.9g, 스테아르산마그네슘 0.6g을 더하고 폴리에틸렌 비닐백에서 혼합하여 타정혼합물을 제조하였다.After mixing 36.9 g of diphenhydramine drug pellets in a polyethylene plastic bag to 39.5 g of the obtained granules, 2.1 g of crospovidone CL-SF, 0.9 g of aspartame, and 0.6 g of magnesium stearate were added and mixed in a polyethylene plastic bag to prepare a tableting mixture. Was prepared.
상기 타정혼합물을 타정압 21~22kN, 27kN, 40~42kN으로 각각 타정하여 직경 9.0mm, 중량 229.2mg의 정제를 얻었다. The tableting mixture was tableted with a tableting pressure of 21 to 22 kN, 27 kN, and 40 to 42 kN, respectively, to obtain tablets having a diameter of 9.0 mm and a weight of 229.2 mg.
[실험예][Experimental Example]
평가 방법Assessment Methods
실시예 및 비교예의 시료에 대하여 다음과 같은 방법으로 경도(kp), 붕해시간(sec) 및 마손도를 평가하였다.The samples of Examples and Comparative Examples were evaluated for hardness (kp), disintegration time (sec), and friability in the following manner.
1. 경도1. Hardness
정제의 경도는 경도측정기(Pharma Test사 PTB 311E)를 사용하여 측정하였고, 5회 측정한 평균값으로 나타내었다.The hardness of the tablet was measured using a hardness tester (Pharma Test, PTB 311E), and was expressed as an average value measured five times.
2. 붕해시간2. Disintegration time
정제의 붕해시간을 붕해측정기(OKADA SEIKO CO., LTD.사 Tricorptester)를 사용하여 측정하였고, 5회 측정한 평균값으로 나타내었다. The disintegration time of the tablet was measured using a disintegration analyzer (OKADA SEIKO CO., LTD., Tricorptester), and expressed as an average value measured five times.
3. 마손도3. Masondo
정제의 마손도는 제11개정 대한민국약전에 기재되어 있는 시험법으로 확인하였다. 즉, 먼저 시험 전후의 정제 중량을 측정하고, 정제 중량의 감소율을 하기 수학식 1에 따라 구하였다.The friability of the tablets was confirmed by the test method described in the 11th revised Korean Pharmacopoeia. That is, first, the tablet weight before and after the test was measured, and the reduction rate of the tablet weight was calculated according to Equation 1 below.
4. 습도 무포장 안정성 시험4. Humidity packaging-free stability test
75% 습도 조건을 위한 포화염 용액은 탈이온수나 정제수를 사용하여 제조하고 약 5% 정도의 염화물이 용액 중에 녹지 않는 상태가 되면 용액이 포화된 상태라고 간주하였다. 이 포화염 용액을 데시케이터에 넣고 습도가 안정화되면 검체를 페트리 디쉬에 넣고 보관하면서 시간경과에 따른 경도 및 붕해시간을 측정하였고, 5회 측정한 평균값을 표기 하였다.Saturated salt solutions for 75% humidity conditions were prepared using deionized or purified water, and when about 5% of chloride was not dissolved in the solution, the solution was considered to be saturated. When this saturated salt solution was put in a desiccator and the humidity stabilized, the specimen was placed in a Petri dish and stored, while the hardness and disintegration time were measured over time, and the average value measured five times was indicated.
5. 관능 시험5. Sensory test
3~5사람의 피험자가 구강 내 혀 위에 정제를 놓고 자연스럽게 붕해시켰다. 그 후의 정제를 구강에 포함해 완전하게 붕해시켰을 때의 복용감을 3단계(○:양호,△:보통, ×:불량)로 판정하였으며, ×의 판정에 대해서는 그 상세한 복용감을 괄호 안에 기재하였다. 3 to 5 subjects placed the tablet on the tongue in the oral cavity and allowed it to disintegrate naturally. When the subsequent tablets were completely disintegrated in the oral cavity, the feeling of dosage was judged in three stages (○: good, △: normal, ×: poor), and for the judgment of ×, the detailed feeling of dosage was described in parentheses.
<실험예 1><Experimental Example 1>
경도, 마손도, 붕해시간 및 타정장애 유무 확인Confirmation of hardness, friability, disintegration time and tabletting disorder
실시예 1 내지 4, 비교예 1 내지 5의 시료의 경도, 마손도, 붕해시간, 타정장애 유무를 확인하여 그 결과를 하기 표 1에 나타내었다. The hardness, friability, disintegration time, and presence or absence of tabletting disorders of the samples of Examples 1 to 4 and Comparative Examples 1 to 5 were checked, and the results are shown in Table 1 below.
6-7kN
6-7kN
11-12kN
11-12kN
상기 표 1의 결과에서 실시예의 시료들은 경도, 마손도, 붕해시간 및 타정장애 유무에서 전반적으로 우수한 것을 알 수 있다. From the results of Table 1, it can be seen that the samples of the examples are generally excellent in hardness, friability, disintegration time, and presence or absence of tabletting disorder.
<실험예 2><Experimental Example 2>
습도 무포장 안정성 시험방법Humidity-free packaging stability test method
상기 실시예 1과 2, 비교예 1과 2에서 제조된 정제에 대한 습도 무포장 안정성을 다음과 같이 시험하였다.The humidity-free packaging stability of the tablets prepared in Examples 1 and 2 and Comparative Examples 1 and 2 was tested as follows.
75% 습도 조건을 위한 포화염 용액은 탈이온수나 정제수를 사용하여 제조하고 약 5% 정도의 염화물이 용액 중에 녹지 않는 상태가 되면 용액이 포화된 상태라고 간주하였다.Saturated salt solutions for 75% humidity conditions were prepared using deionized or purified water, and when about 5% of chloride was not dissolved in the solution, the solution was considered to be saturated.
이 포화염 용액을 데시케이터에 넣고 습도가 안정화되면 검체를 페트리 디쉬에 넣고 보관하면서 시간경과에 따른 경도 및 붕해시간을 측정하였고, 5회 측정한 평균값을 하기 표 2와 3에 각각 나타내었다.When the saturated salt solution was put in a desiccator and the humidity was stabilized, the specimen was placed in a Petri dish and stored, while the hardness and disintegration time were measured over time, and the average values measured five times are shown in Tables 2 and 3, respectively.
상기 표 2와 3의 결과에서, 시간이 경과하였을 때 실시예의 시료들이 비교예의 시료들에 비하여 안정성이 우수한 것을 알 수 있다.From the results of Tables 2 and 3, it can be seen that the samples of the example have superior stability compared to the samples of the comparative example over time.
<실험예 3><Experimental Example 3>
경도, 마손도 및 붕해시간 확인Check hardness, friability and disintegration time
실시예 5와 비교예 6의 시료에 대하여 경도, 마손도, 붕해시간을 확인하여 그 결과를 하기 표 4에 나타내었다. For the samples of Example 5 and Comparative Example 6, hardness, friability, and disintegration time were checked, and the results are shown in Table 4 below.
상기 표 4의 결과에서 확인되는 바와 같이, 실시예 5와 비교예 6의 시료는 동일한 경도에서 실시예 5의 시료가 10초 빠른 붕해시간을 나타내었다.As can be seen from the results of Table 4, the samples of Example 5 and Comparative Example 6 exhibited a disintegration time of 10 seconds faster than the sample of Example 5 at the same hardness.
<실험예 4><Experimental Example 4>
타정성 확인Confirmation of tabletting
실시예 5와 비교예 6의 시료에 대하여 타정압에 따른 경도를 확인하였다. 그 결과를 하기 표 5 및 도 1에 나타내었다.For the samples of Example 5 and Comparative Example 6, the hardness according to the tablet pressure was confirmed. The results are shown in Table 5 and Fig. 1 below.
상기 표 5와 도 1의 결과에서 확인되는 바와 같이, 실시예 5의 정제는 비교예 6의 정제에 비하여 낮은 타정압에서 높은 경도를 나타내었다. 이는 표면이 개질된 주부형제를 사용함으로써 개질되지 않은 주부형제를 사용했을 때에 비해 타정성이 우수해졌음을 보여준다.As can be seen from the results of Table 5 and FIG. 1, the tablet of Example 5 exhibited higher hardness at a lower tableting pressure than the tablet of Comparative Example 6. This shows that the use of the surface-modified house-type agent improved tabletting properties compared to the case of using the unmodified house-type agent.
<실험예 5><Experimental Example 5>
관능 시험Sensory test
실시예 5는 붕해가 빨라 복용감이 양호하고, 비교에 6은 타정압을 많이 받은 만큼 펠렛 코팅이 살짝 깨져 약물의 쓴 맛이 느껴진다거나, 잔류감이나 껄끄러움이 느껴진다는 평가를 받았다. In Example 5, the disintegration was fast and the feeling was good, and in comparison, the pellet coating was slightly cracked as much as the tableting pressure was received, so that the bitter taste of the drug was felt, or residual feeling or greasy feeling was felt.
Claims (8)
상기 단계에서 얻은 표면 개질된 주부형제에 옥수수전분, 메타규산알루민산마그네슘을 혼합한 후 과립화하여 과립물을 얻는 단계;
상기 과립물에 약물과 붕해제를 혼합해서 타정혼합물을 얻는 단계; 및
상기 타정혼합물을 타정해서 구강붕해정을 얻는 단계를 포함하며,
상기 구강붕해정 중에는 상기 표면 개질된 주부형제가 35~80중량%로 포함되는 것을 특징으로 하는, 구강붕해정의 제조방법.The surface of the housewife is modified by wet granulation using an ethyl cellulose solution in which ethyl cellulose having a viscosity of 6 to 55 cps is dispersed in a solvent, but the housewife is composed of mannitol and light anhydrous silicic acid as a fluidizing agent, and the housewife versus ethyl cellulose Preparation step of using the solution in a weight ratio of 20:1 to 30:1 based on solid content, a surface-modified housewife;
Mixing corn starch and magnesium metasilicate aluminate with the surface-modified housewife obtained in the above step, and then granulating to obtain granules;
Mixing a drug and a disintegrant in the granules to obtain a tableting mixture; And
Comprising the step of obtaining an oral disintegrating tablet by tableting the tableting mixture,
In the oral disintegrating tablet, characterized in that the surface-modified housewife is contained in an amount of 35 to 80% by weight.
상기 경질무수규산은 상기 주부형제 총 중량 중에 0.1~1.0중량%로 포함되는 것을 특징으로 하는 구강붕해정의 제조방법.The method of claim 1,
The light anhydrous silicic acid is a method for producing an oral disintegrating tablet, characterized in that contained in 0.1 to 1.0% by weight based on the total weight of the housewife.
상기 정제는 결합제, 활택제, 감미제, 부(副)부형제, 계면활성제, 산미료, 발포제, 안정화제, 착향제(향료), 착색제, 방부제, pH 조절제 중 1종 이상을 포함하는 것을 특징으로 하는 구강붕해정의 제조방법.
The method of claim 1,
The tablet is oral, characterized in that it contains at least one of a binder, a lubricant, a sweetener, an auxiliary excipient, a surfactant, an acidulant, a foaming agent, a stabilizer, a flavoring agent (fragrance), a colorant, a preservative, and a pH adjusting agent. Method for producing disintegrating tablets.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020180055753A KR102149080B1 (en) | 2018-05-16 | 2018-05-16 | Orally Disintegrating Tablet comprising sugar or sugar alcohol granules reformed with ethyl cellulose |
| JP2019080927A JP6752927B2 (en) | 2018-05-16 | 2019-04-22 | Manufacturing method of orally disintegrating tablets |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020180055753A KR102149080B1 (en) | 2018-05-16 | 2018-05-16 | Orally Disintegrating Tablet comprising sugar or sugar alcohol granules reformed with ethyl cellulose |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20190131192A KR20190131192A (en) | 2019-11-26 |
| KR102149080B1 true KR102149080B1 (en) | 2020-08-27 |
Family
ID=68612859
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020180055753A KR102149080B1 (en) | 2018-05-16 | 2018-05-16 | Orally Disintegrating Tablet comprising sugar or sugar alcohol granules reformed with ethyl cellulose |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JP6752927B2 (en) |
| KR (1) | KR102149080B1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115462495A (en) * | 2022-09-06 | 2022-12-13 | 江苏艾兰得营养品有限公司 | Micro effervescent tablet and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101704156B1 (en) * | 2008-11-25 | 2017-02-07 | 미쓰비시 타나베 파마 코퍼레이션 | Mixture for producing orally rapidly disintegrating tablet |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20050118775A (en) | 2004-06-15 | 2005-12-20 | 주식회사 태평양 | Orally disintegrating tablet utilizing crystallized solid bridge between sugars and drug particles |
| JP2006022040A (en) * | 2004-07-08 | 2006-01-26 | Towa Yakuhin Kk | Simvastatin solid preparation having high stability |
| CN101868228B (en) | 2007-11-21 | 2016-12-07 | 大日本住友制药株式会社 | Orally disintegrating tablet |
| JP5517327B2 (en) * | 2008-12-16 | 2014-06-11 | 日医工株式会社 | Composition for orally disintegrating tablets |
| KR20130009416A (en) | 2011-07-15 | 2013-01-23 | 성균관대학교산학협력단 | Sustained-release microparticle of pramipexole and fast dissolving oral tablet containing the same |
| KR101531030B1 (en) | 2013-12-31 | 2015-06-24 | 코오롱제약주식회사 | Orally disintegrating tablet containing mirtazapine |
| EP3449912B1 (en) * | 2016-06-16 | 2024-03-06 | Towa Pharmaceutical Co., Ltd. | Orally disintegrating tablet |
-
2018
- 2018-05-16 KR KR1020180055753A patent/KR102149080B1/en active IP Right Grant
-
2019
- 2019-04-22 JP JP2019080927A patent/JP6752927B2/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101704156B1 (en) * | 2008-11-25 | 2017-02-07 | 미쓰비시 타나베 파마 코퍼레이션 | Mixture for producing orally rapidly disintegrating tablet |
Also Published As
| Publication number | Publication date |
|---|---|
| JP6752927B2 (en) | 2020-09-09 |
| JP2019199463A (en) | 2019-11-21 |
| KR20190131192A (en) | 2019-11-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8425935B2 (en) | Pharmaceutical formulation for producing rapidly disintegrating tablets | |
| EP2218443B1 (en) | Orally disintegrating tablet | |
| EP1980272B1 (en) | Orally-disintegrating tablet and manufacturing method thereof | |
| JP5074190B2 (en) | Orally rapidly disintegrating tablets | |
| KR101099176B1 (en) | Tablet quickly melting in oral cavity | |
| JP5296456B2 (en) | Irbesartan-containing pharmaceutical composition with good dissolution and orally disintegrating tablet | |
| JP2001058944A (en) | Rapidly disintegrating solid formulation | |
| KR20130030306A (en) | Pharmaceutical compositions | |
| US8426451B2 (en) | Oral solid preparation and method of manufacturing the same | |
| JP6919119B2 (en) | A compressed solid pharmaceutical composition containing a γ-aminobutyric acid derivative substituted at the 3-position. | |
| EP1773292B1 (en) | Rapidly disintegrating orodispersible composition containing nonfilamentous coprocessed polyols particles and silicified microcrystalline cellulose | |
| US8568780B2 (en) | Pharmaceutical formulation for the production of rapidly disintegrating tablets | |
| US20110014286A1 (en) | Mixture for producing rapidly disintegrating tablets | |
| JP7336388B2 (en) | Tablet and its manufacturing method | |
| WO2005120463A1 (en) | Rapidly disintegrating tablets of risperidone | |
| JP2002255796A (en) | Rapidly disintegrating tablet in oral cavity and method for producing the same | |
| KR102149080B1 (en) | Orally Disintegrating Tablet comprising sugar or sugar alcohol granules reformed with ethyl cellulose | |
| JP2018108950A (en) | Levocetirizine hydrochloride-containing orally disintegrating tablet | |
| KR101833250B1 (en) | Spherical extruded granule comprising an active ingredient having a low melting point, tablet for oral administration comprising the same, and method for the preparation thereof | |
| Saharan | Excipients for fast dissolving/disintegrating tablets | |
| JP6151413B2 (en) | Irbesartan-containing pharmaceutical composition with good dissolution and orally disintegrating tablet | |
| JP2015110663A (en) | Irbesartan-containing pharmaceutical composition with excellent elution property and orally disintegrable tablet | |
| JP6128160B2 (en) | Method for producing orally disintegrating tablets | |
| JP7379189B2 (en) | Coated particles containing vildagliptin, orally disintegrating tablets containing vildagliptin, method for producing coated particles containing vildagliptin, and method for producing orally disintegrating tablets containing vildagliptin | |
| JP5714652B2 (en) | Irbesartan-containing pharmaceutical composition with good dissolution and orally disintegrating tablet |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| E902 | Notification of reason for refusal | ||
| AMND | Amendment | ||
| E601 | Decision to refuse application | ||
| X091 | Application refused [patent] | ||
| AMND | Amendment | ||
| X701 | Decision to grant (after re-examination) | ||
| R401 | Registration of restoration |