KR20120073111A - Tablet - Google Patents
Tablet Download PDFInfo
- Publication number
- KR20120073111A KR20120073111A KR1020110138800A KR20110138800A KR20120073111A KR 20120073111 A KR20120073111 A KR 20120073111A KR 1020110138800 A KR1020110138800 A KR 1020110138800A KR 20110138800 A KR20110138800 A KR 20110138800A KR 20120073111 A KR20120073111 A KR 20120073111A
- Authority
- KR
- South Korea
- Prior art keywords
- tablet
- component
- granules
- dry granulated
- disintegration
- Prior art date
Links
- 239000008187 granular material Substances 0.000 claims abstract description 94
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims abstract description 27
- 229960001680 ibuprofen Drugs 0.000 claims abstract description 27
- 239000003814 drug Substances 0.000 claims abstract description 21
- 229940079593 drug Drugs 0.000 claims abstract description 20
- 229920002785 Croscarmellose sodium Polymers 0.000 claims abstract description 15
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims abstract description 15
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 claims abstract description 15
- 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 abstract description 15
- 229960001681 croscarmellose sodium Drugs 0.000 claims abstract description 15
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims abstract description 15
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims abstract description 15
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims abstract description 15
- 229940071676 hydroxypropylcellulose Drugs 0.000 claims abstract description 15
- 229960002009 naproxen Drugs 0.000 claims abstract description 15
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims abstract description 15
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims abstract description 14
- 229920002472 Starch Polymers 0.000 claims abstract description 14
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 claims abstract description 14
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims abstract description 14
- 229950008138 carmellose Drugs 0.000 claims abstract description 14
- 239000008107 starch Substances 0.000 claims abstract description 14
- 235000019698 starch Nutrition 0.000 claims abstract description 14
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 claims abstract description 13
- 229960000991 ketoprofen Drugs 0.000 claims abstract description 13
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims abstract description 8
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims abstract description 8
- 239000011734 sodium Substances 0.000 claims abstract description 8
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 8
- 238000006467 substitution reaction Methods 0.000 claims abstract description 4
- 239000002245 particle Substances 0.000 claims description 21
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 11
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 9
- 229960000913 crospovidone Drugs 0.000 claims description 8
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 8
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 abstract description 16
- 235000019260 propionic acid Nutrition 0.000 abstract description 8
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 abstract description 8
- 239000007884 disintegrant Substances 0.000 abstract description 3
- 229940121363 anti-inflammatory agent Drugs 0.000 abstract 1
- 239000002260 anti-inflammatory agent Substances 0.000 abstract 1
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 28
- 239000000843 powder Substances 0.000 description 23
- 238000002156 mixing Methods 0.000 description 21
- 239000000203 mixture Substances 0.000 description 15
- 235000019359 magnesium stearate Nutrition 0.000 description 14
- 239000000654 additive Substances 0.000 description 13
- 239000011812 mixed powder Substances 0.000 description 13
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 12
- -1 tiaramid Chemical compound 0.000 description 9
- 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 8
- 229940047127 fiore Drugs 0.000 description 8
- 239000008101 lactose Substances 0.000 description 8
- 238000005469 granulation Methods 0.000 description 7
- 230000003179 granulation Effects 0.000 description 7
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 229960005489 paracetamol Drugs 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 229930006000 Sucrose Natural products 0.000 description 5
- 230000000996 additive effect Effects 0.000 description 5
- 229940024546 aluminum hydroxide gel Drugs 0.000 description 5
- SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 description 5
- 229960001948 caffeine Drugs 0.000 description 5
- 238000007906 compression Methods 0.000 description 5
- 230000006835 compression Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000011049 filling Methods 0.000 description 5
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 239000005720 sucrose Substances 0.000 description 5
- 235000000346 sugar Nutrition 0.000 description 5
- 239000011230 binding agent Substances 0.000 description 4
- 229920002678 cellulose Polymers 0.000 description 4
- 235000010980 cellulose Nutrition 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 4
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 4
- 238000004513 sizing Methods 0.000 description 4
- 150000008163 sugars Chemical class 0.000 description 4
- 230000000202 analgesic effect Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 229960000520 diphenhydramine Drugs 0.000 description 3
- 238000007908 dry granulation Methods 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
- 239000000314 lubricant Substances 0.000 description 3
- 239000011976 maleic acid Substances 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 239000002356 single layer Substances 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000005550 wet granulation Methods 0.000 description 3
- 244000215068 Acacia senegal Species 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
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 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 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 235000006679 Mentha X verticillata Nutrition 0.000 description 2
- 235000002899 Mentha suaveolens Nutrition 0.000 description 2
- 235000001636 Mentha x rotundifolia Nutrition 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 229920002125 Sokalan® Polymers 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
- 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 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000001754 anti-pyretic effect Effects 0.000 description 2
- 239000003907 antipyretic analgesic agent Substances 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 2
- 229960000428 carbinoxamine Drugs 0.000 description 2
- SOYKEARSMXGVTM-UHFFFAOYSA-N chlorphenamine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 SOYKEARSMXGVTM-UHFFFAOYSA-N 0.000 description 2
- 229960003291 chlorphenamine Drugs 0.000 description 2
- 229940124579 cold medicine Drugs 0.000 description 2
- 238000013329 compounding Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- SNDDIRAXSDUVKW-URVXVIKDSA-N dextromethorphan hcl Chemical compound Cl.C([C@@H]12)CCC[C@]11CCN(C)[C@H]2CC2=CC=C(OC)C=C21 SNDDIRAXSDUVKW-URVXVIKDSA-N 0.000 description 2
- 229960005257 dextromethorphan hydrochloride Drugs 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 238000009477 fluid bed granulation Methods 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 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 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 239000004014 plasticizer Substances 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- 239000003232 water-soluble binding agent Substances 0.000 description 2
- 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 1
- 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
- FMCGSUUBYTWNDP-ONGXEEELSA-N (1R,2S)-2-(dimethylamino)-1-phenyl-1-propanol Chemical compound CN(C)[C@@H](C)[C@H](O)C1=CC=CC=C1 FMCGSUUBYTWNDP-ONGXEEELSA-N 0.000 description 1
- UHSXRTHJCJGEKG-UQKRIMTDSA-N (1s)-1-[(3,4,5-trimethoxyphenyl)methyl]-1,2,3,4-tetrahydroisoquinolin-2-ium-6,7-diol;chloride Chemical compound Cl.COC1=C(OC)C(OC)=CC(C[C@H]2C3=CC(O)=C(O)C=C3CCN2)=C1 UHSXRTHJCJGEKG-UQKRIMTDSA-N 0.000 description 1
- 239000001100 (2S)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one Substances 0.000 description 1
- DKSZLDSPXIWGFO-BLOJGBSASA-N (4r,4ar,7s,7ar,12bs)-9-methoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7-ol;phosphoric acid;hydrate Chemical compound O.OP(O)(O)=O.OP(O)(O)=O.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC DKSZLDSPXIWGFO-BLOJGBSASA-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
- PMGQWSIVQFOFOQ-BDUVBVHRSA-N (e)-but-2-enedioic acid;(2r)-2-[2-[1-(4-chlorophenyl)-1-phenylethoxy]ethyl]-1-methylpyrrolidine Chemical compound OC(=O)\C=C\C(O)=O.CN1CCC[C@@H]1CCOC(C)(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 PMGQWSIVQFOFOQ-BDUVBVHRSA-N 0.000 description 1
- 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 1
- CIVCELMLGDGMKZ-UHFFFAOYSA-N 2,4-dichloro-6-methylpyridine-3-carboxylic acid Chemical compound CC1=CC(Cl)=C(C(O)=O)C(Cl)=N1 CIVCELMLGDGMKZ-UHFFFAOYSA-N 0.000 description 1
- WYUYEJNGHIOFOC-VVTVMFAVSA-N 2-[(z)-1-(4-methylphenyl)-3-pyrrolidin-1-ylprop-1-enyl]pyridine;hydrochloride Chemical compound Cl.C1=CC(C)=CC=C1C(\C=1N=CC=CC=1)=C\CN1CCCC1 WYUYEJNGHIOFOC-VVTVMFAVSA-N 0.000 description 1
- FSSICIQKZGUEAE-UHFFFAOYSA-N 2-[benzyl(pyridin-2-yl)amino]ethyl-dimethylazanium;chloride Chemical compound Cl.C=1C=CC=NC=1N(CCN(C)C)CC1=CC=CC=C1 FSSICIQKZGUEAE-UHFFFAOYSA-N 0.000 description 1
- ULXKXLZEOGLCRJ-UHFFFAOYSA-N 2-azaniumyl-3-ethylsulfanylpropanoate Chemical compound CCSCC(N)C(O)=O ULXKXLZEOGLCRJ-UHFFFAOYSA-N 0.000 description 1
- QOLHOCYZKJILAV-UHFFFAOYSA-N 5-[(3-carboxy-4-hydroxyphenyl)methyl]-2-hydroxybenzoic acid;n,n-dimethyl-1-phenothiazin-10-ylpropan-2-amine Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1.C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1.C1=C(O)C(C(=O)O)=CC(CC=2C=C(C(O)=CC=2)C(O)=O)=C1 QOLHOCYZKJILAV-UHFFFAOYSA-N 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
- RMMXTBMQSGEXHJ-UHFFFAOYSA-N Aminophenazone Chemical compound O=C1C(N(C)C)=C(C)N(C)N1C1=CC=CC=C1 RMMXTBMQSGEXHJ-UHFFFAOYSA-N 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- MJOVRQAFPQBODC-UHFFFAOYSA-N Cl.C1(=CC=CC=C1)C1=C(C(OC=C1)C=O)C1=CC=CC=C1 Chemical compound Cl.C1(=CC=CC=C1)C1=C(C(OC=C1)C=O)C1=CC=CC=C1 MJOVRQAFPQBODC-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 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 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 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 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- WKZITTRQXFNUNO-UHFFFAOYSA-N Difeterol hydrochloride Chemical compound Cl.C=1C=CC=CC=1C(C=1C=CC=CC=1)OCCN(C)C(C)C(O)C1=CC=CC=C1 WKZITTRQXFNUNO-UHFFFAOYSA-N 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- 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 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920003116 HPC-SSL Polymers 0.000 description 1
- QUQPHWDTPGMPEX-UHFFFAOYSA-N Hesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(COC4C(C(O)C(O)C(C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-UHFFFAOYSA-N 0.000 description 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
- 239000004201 L-cysteine Substances 0.000 description 1
- 235000013878 L-cysteine Nutrition 0.000 description 1
- 235000019501 Lemon oil Nutrition 0.000 description 1
- 241000408529 Libra Species 0.000 description 1
- 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 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- 244000183278 Nephelium litchi Species 0.000 description 1
- 235000015742 Nephelium litchi Nutrition 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 239000004373 Pullulan Substances 0.000 description 1
- 229920001218 Pullulan Polymers 0.000 description 1
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 1
- GBFLZEXEOZUWRN-VKHMYHEASA-N S-carboxymethyl-L-cysteine Chemical compound OC(=O)[C@@H](N)CSCC(O)=O GBFLZEXEOZUWRN-VKHMYHEASA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 239000004376 Sucralose Substances 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 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 1
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 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
- 229960004308 acetylcysteine Drugs 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 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 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- BWZOPYPOZJBVLQ-UHFFFAOYSA-K aluminium glycinate Chemical compound O[Al+]O.NCC([O-])=O BWZOPYPOZJBVLQ-UHFFFAOYSA-K 0.000 description 1
- JBDGDEWWOUBZPM-XYPYZODXSA-N ambroxol Chemical compound NC1=C(Br)C=C(Br)C=C1CN[C@@H]1CC[C@@H](O)CC1 JBDGDEWWOUBZPM-XYPYZODXSA-N 0.000 description 1
- 229960005174 ambroxol Drugs 0.000 description 1
- 229960000212 aminophenazone Drugs 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000000954 anitussive effect Effects 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000001458 anti-acid effect Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 229940125716 antipyretic agent Drugs 0.000 description 1
- 229940124584 antitussives Drugs 0.000 description 1
- KSUUMAWCGDNLFK-UHFFFAOYSA-N apronal Chemical compound C=CCC(C(C)C)C(=O)NC(N)=O KSUUMAWCGDNLFK-UHFFFAOYSA-N 0.000 description 1
- 229960004459 apronal Drugs 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 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 1
- 229960003438 aspartame Drugs 0.000 description 1
- QUQPHWDTPGMPEX-UTWYECKDSA-N aurantiamarin Natural products COc1ccc(cc1O)[C@H]1CC(=O)c2c(O)cc(O[C@@H]3O[C@H](CO[C@@H]4O[C@@H](C)[C@H](O)[C@@H](O)[C@H]4O)[C@@H](O)[C@H](O)[C@H]3O)cc2O1 QUQPHWDTPGMPEX-UTWYECKDSA-N 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- 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 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 235000010376 calcium ascorbate Nutrition 0.000 description 1
- 229940047036 calcium ascorbate Drugs 0.000 description 1
- 239000011692 calcium ascorbate Substances 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
- BLORRZQTHNGFTI-ZZMNMWMASA-L calcium-L-ascorbate Chemical compound [Ca+2].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] BLORRZQTHNGFTI-ZZMNMWMASA-L 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- OJFSXZCBGQGRNV-UHFFFAOYSA-N carbinoxamine Chemical compound C=1C=CC=NC=1C(OCCN(C)C)C1=CC=C(Cl)C=C1 OJFSXZCBGQGRNV-UHFFFAOYSA-N 0.000 description 1
- 229960004399 carbocisteine Drugs 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229960002689 clemastine fumarate Drugs 0.000 description 1
- APSNPMVGBGZYAJ-GLOOOPAXSA-N clematine Natural products COc1cc(ccc1O)[C@@H]2CC(=O)c3c(O)cc(O[C@@H]4O[C@H](CO[C@H]5O[C@@H](C)[C@H](O)[C@@H](O)[C@H]5O)[C@@H](O)[C@H](O)[C@H]4O)cc3O2 APSNPMVGBGZYAJ-GLOOOPAXSA-N 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229960004415 codeine phosphate Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000000748 compression moulding Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 229960001056 dimemorfan Drugs 0.000 description 1
- KBEZZLAAKIIPFK-NJAFHUGGSA-N dimemorfan Chemical compound C1C2=CC=C(C)C=C2[C@@]23CCN(C)[C@@H]1[C@H]2CCCC3 KBEZZLAAKIIPFK-NJAFHUGGSA-N 0.000 description 1
- 229960000525 diphenhydramine hydrochloride Drugs 0.000 description 1
- 229960000879 diphenylpyraline Drugs 0.000 description 1
- OWQUZNMMYNAXSL-UHFFFAOYSA-N diphenylpyraline Chemical compound C1CN(C)CCC1OC(C=1C=CC=CC=1)C1=CC=CC=C1 OWQUZNMMYNAXSL-UHFFFAOYSA-N 0.000 description 1
- KCIDZIIHRGYJAE-YGFYJFDDSA-L dipotassium;[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] phosphate Chemical compound [K+].[K+].OC[C@H]1O[C@H](OP([O-])([O-])=O)[C@H](O)[C@@H](O)[C@H]1O KCIDZIIHRGYJAE-YGFYJFDDSA-L 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 229940005636 dl- methylephedrine Drugs 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
- 229960004667 ethyl cellulose Drugs 0.000 description 1
- 229940031005 ethyl cysteine Drugs 0.000 description 1
- 235000010944 ethyl methyl cellulose Nutrition 0.000 description 1
- 230000002964 excitative effect Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000003172 expectorant agent Substances 0.000 description 1
- 230000003419 expectorant effect Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000001087 glyceryl triacetate Substances 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- 229940025878 hesperidin Drugs 0.000 description 1
- VUYDGVRIQRPHFX-UHFFFAOYSA-N hesperidin Natural products COc1cc(ccc1O)C2CC(=O)c3c(O)cc(OC4OC(COC5OC(O)C(O)C(O)C5O)C(O)C(O)C4O)cc3O2 VUYDGVRIQRPHFX-UHFFFAOYSA-N 0.000 description 1
- QUQPHWDTPGMPEX-QJBIFVCTSA-N hesperidin Chemical compound C1=C(O)C(OC)=CC=C1[C@H]1OC2=CC(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO[C@H]4[C@@H]([C@H](O)[C@@H](O)[C@H](C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-QJBIFVCTSA-N 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000000832 lactitol Substances 0.000 description 1
- 235000010448 lactitol Nutrition 0.000 description 1
- 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 1
- 229960003451 lactitol Drugs 0.000 description 1
- 239000010501 lemon oil Substances 0.000 description 1
- 229940087305 limonene Drugs 0.000 description 1
- 235000001510 limonene Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 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 1
- 229940035436 maltitol Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- FQQIIPAOSKSOJM-UHFFFAOYSA-N mebhydrolin Chemical compound C1N(C)CCC2=C1C1=CC=CC=C1N2CC1=CC=CC=C1 FQQIIPAOSKSOJM-UHFFFAOYSA-N 0.000 description 1
- 229960004934 mebhydrolin Drugs 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- FGSJNNQVSUVTPW-UHFFFAOYSA-N methoxyphenamine hydrochloride Chemical compound Cl.CNC(C)CC1=CC=CC=C1OC FGSJNNQVSUVTPW-UHFFFAOYSA-N 0.000 description 1
- 229960000659 methoxyphenamine hydrochloride Drugs 0.000 description 1
- 229960002900 methylcellulose Drugs 0.000 description 1
- 229920003087 methylethyl cellulose Polymers 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- ARGKVCXINMKCAZ-UHFFFAOYSA-N neohesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(CO)O3)OC3C(C(O)C(O)C(C)O3)O)=CC(O)=C2C(=O)C1 ARGKVCXINMKCAZ-UHFFFAOYSA-N 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
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229940068984 polyvinyl alcohol Drugs 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 238000007781 pre-processing Methods 0.000 description 1
- 235000019423 pullulan Nutrition 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000008213 purified water Substances 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
- 238000007670 refining Methods 0.000 description 1
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
- 229960000371 rofecoxib Drugs 0.000 description 1
- 238000009490 roller compaction Methods 0.000 description 1
- 238000010079 rubber tapping Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000010008 shearing Methods 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
- 229960003885 sodium benzoate Drugs 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000008117 stearic acid Substances 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
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- JZRWCGZRTZMZEH-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 239000001069 triethyl citrate Substances 0.000 description 1
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 1
- 235000013769 triethyl citrate Nutrition 0.000 description 1
- 229960001593 triprolidine hydrochloride Drugs 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
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
- A61K9/20—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
- 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
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
본 발명은, 프로피온산계(系) 비(非)스테로이드 항염증제(抗炎症劑)를 함유하는 정제(錠劑)에 관한 것이다.The present invention relates to a tablet containing a propionic acid nonsteroidal anti-inflammatory agent.
이부프로펜 등의 프로피온산계 비스테로이드 항염증제는, 우수한 소염, 진통, 해열 작용을 가지며, 부작용이 비교적 적기 때문에 진통?해열제 및 감기약의 성분으로서 널리 사용되고 있다. 그러나, 프로피온산계 비스테로이드 항염증제는, 수난용성(水難溶性)의 약물이 많고, 그대로는 소화관에서의 흡수성, 특히 속효성(速效性)에 어려움이 있다. 이들의 약물을 제정화(製錠化)하는 경우, 소화관에서 약물을 즉석에서 흡수시키기 위해서는, 약물을 위(胃) 내에서 신속하게 용해시켜야 한다. 그를 위해서는, 전단계(前段階)인 정제의 붕괴가 신속하게 행해져야 한다. 그러나, 일반적으로 수난용성 약물은 정제 내로의 물의 침투를 방해하고, 정제의 붕괴를 지연시켜 버리는 문제가 있다.Propionic acid-based nonsteroidal anti-inflammatory agents such as ibuprofen have excellent anti-inflammatory, analgesic and antipyretic effects, and are relatively widely used as components of analgesic and antipyretic agents and cold medicines because of their relatively low side effects. However, propionic acid-based nonsteroidal anti-inflammatory drugs are poorly water-soluble, and they are difficult to absorb in the digestive tract, in particular, to be fast-acting. When these drugs are refined, the drugs must be dissolved quickly in the stomach in order to absorb the drugs in the digestive tract immediately. For that purpose, the disintegration of the preliminary tablet must be done quickly. However, poorly water-soluble drugs generally have a problem of preventing the penetration of water into the tablet and delaying the disintegration of the tablet.
또한, 이부프로펜 등의 프로피온산계 비스테로이드 항염증제는, 원료분말(原末)인 그대로 직접 타정(打錠)하는 경우, 배합 비율이 높으면 타정기 표면에의 부착, 부피가 큼에 의한 타정구(打錠臼) 내로의 충전 불량, 정제의 취약성에 의한 보관 또는 수송시에 있어서의 일그러짐 등의 문제가 생기는 것도 알려져 있다. 이와 같은 문제를 회피하기 위해, 일반적으로 상기 약제는 제정화(製錠化)의 전(前) 공정에서 다른 부형제나 결합제와 함께 조립(造粒)되는 것이 많다.In addition, propionic acid-based nonsteroidal anti-inflammatory drugs such as ibuprofen, when directly tableted as they are raw material powders, have high tableting ratios, and may be formed on the surface of a tableting machine, It is also known to cause problems such as poor filling in the inside of the product, distortion during storage or transportation due to the weakness of the tablet. In order to avoid such a problem, in general, the medicament is often assembled with other excipients or binders in the pre-processing step of refining.
프로피온산계 비스테로이드 항염증제의 붕괴성 및 제조성에 관한 상기 과제를 해결하는 것을 목적으로 하여, 종래로부터 여러 가지의 기술이 검토되고 있다. 예를 들면, 일본 특개소56-110612호 공보(특허 문헌 1)에는, 난용성 약물을 폴리비닐피롤리돈이나 히드록시프로필셀룰로오스 등과 (또는 나아가 계면활성제와) 배합하고, 유동층 조립법에 의해 조립한 압축 성형물이 제안되어 있고, 스프레이 드라이법이나 그 밖에 습식 조립법을 이용한 압축 성형물에 비하여, 우수한 붕괴?용해성을 나타낸 취지가 기재되어 있다.In order to solve the said subject regarding the disintegration property and the manufacturability of a propionic acid nonsteroidal anti-inflammatory agent, various techniques are conventionally examined. For example, Japanese Patent Application Laid-Open No. 56-110612 (Patent Document 1) includes a poorly water-soluble drug blended with polyvinylpyrrolidone, hydroxypropyl cellulose, or the like (or with a surfactant), and granulated by a fluidized bed granulation method. Compression molded products have been proposed, and the purpose of showing excellent disintegration and solubility compared to compression molded products using a spray drying method or a wet granulation method is described.
[특허 문헌][Patent Document]
특허 문헌 1 : 일본 특개소56-110612호 공보Patent Document 1: Japanese Patent Application Laid-Open No. 56-110612
종래의 유동층 조립은 소망하는 입자를 얻기 위한 조건 설정이 번잡하고, 제제화에 시간을 필요로 한다. 게다가, 상세한 메커니즘은 분명하지 않지만, 본 발명자의 검토에서는, 수난용성 약물 중에서도, 이부프로펜, 나프록센, 케토프로펜에 한하여서는, 히드록시프로필셀룰로오스 등의 범용의 결합제액(液)을 사용하여 유동층 조립이나 다른 습식 조립을 행함으로써 정제의 붕괴성이 현저하게 저하되는 것을 알았다.Conventional fluid bed granulation is complicated to set conditions for obtaining the desired particles, and requires time for formulation. In addition, although the detailed mechanism is not clear, in the examination of this inventor, even among poorly water-soluble drugs, only ibuprofen, naproxen, and ketoprofen, using general-purpose binder liquids, such as hydroxypropyl cellulose, are used for fluid bed granulation, By performing other wet granulation, it was found that the disintegration property of the tablet was remarkably reduced.
이와 같이, 종래의 기술에서는, 정제의 붕괴성과 제조성을 양립시키는, 이부프로펜, 나프록센 또는 케토프로펜을 함유하는 타정용 과립(顆粒), 및 이부프로펜, 나프록센 또는 케토프로펜을 함유하는 정제를 조제할 수 있는 기술은 없었다. 또한, 종래 기술에서 나타나는 붕괴성의 레벨은 아직도 만족할 수 있는 것이 아니고, 종래 기술의 붕괴성을 상회하는 정제가 요망되고 있다. 본 발명은 상기 사정을 감안하여 이루어진 것으로, 정제의 붕괴성과 제조성을 양립시키는, 이부프로펜, 나프록센 또는 케토프로펜을 함유하는 정제를 제공하는 것을 목적으로 한다.As described above, according to the related art, a tablet containing granules containing ibuprofen, naproxen or ketoprofen, and a tablet containing ibuprofen, naproxen or ketoprofen can be prepared to make tablets both disintegratable and manufacturable. There was no technology. Moreover, the level of disintegration exhibited by the prior art is still not satisfactory, and purification beyond the disintegration of the prior art is desired. This invention is made | formed in view of the said situation, and an object of this invention is to provide the tablet containing ibuprofen, naproxen, or ketoprofen which makes both tablet disintegration and manufacturability compatible.
본 발명자들은, 상기 목적을 달성하기 위해 예의 검토한 결과, (A) 이부프로펜, 나프록센 및 케토프로펜으로부터 선택되는 약물을 함유하는 타정용 과립을 조제할 때에, 상기 (A) 이부프로펜, 나프록센 및 케토프로펜으로부터 선택되는 약물과, (B) 저치환도 히드록시프로필셀룰로오스, 카르멜로스, 크로스카르멜로스나트륨, 크로스포비돈 및 카르복시메틸스타치나트륨으로부터 선택되는 붕괴제를, (B)/(A)로 표시되는 질량비가 0.1 내지 0.7이 되는 범위에서 혼합하고, 습식 조립이 아니라, 건식 조립한 건식 조립 과립으로 함으로써, 이것을 배합한 정제는, 우수한 붕괴성을 가지며, 게다가 타정시에는 우수한 과립 강도를 나타내고, 붕괴성과 제조성을 양립할 수 있는 것을 지견하여, 본 발명을 이루는데 이른 것이다.MEANS TO SOLVE THE PROBLEM The present inventors earnestly examined in order to achieve the said objective, When (A) tabletting granules containing the drug chosen from ibuprofen, naproxen, and ketoprofen, (A) ibuprofen, naproxen, and ketopro A drug selected from a pen and a disintegrating agent selected from (B) low-substituted hydroxypropyl cellulose, carmellose, croscarmellose sodium, crospovidone and carboxymethyl starch sodium are represented by (B) / (A) By mixing in a range in which the mass ratio is 0.1 to 0.7 and making dry granulated granules instead of wet granulation, the tablets blended with these have excellent disintegration properties, and show excellent granular strength when tableting and disintegrate. The inventors have found that both the performance and the manufacturability can be achieved, and the present invention has been achieved.
따라서 본 발명은 하기 정제를 제공한다.The present invention therefore provides the following tablets.
[1]. (A) 이부프로펜, 나프록센 및 케토프로펜으로부터 선택되는 약물과, (B) 저치환도 히드록시프로필셀룰로오스, 카르멜로스, 크로스카르멜로스나트륨, 크로스포비돈 및 카르복시메틸스타치나트륨으로부터 선택되는 붕괴제를 함유하고, (B)/(A)로 표시되는 질량비가 0.1 내지 0.7이고, (A)성분과 (B)성분을 상기 비율로 혼합하고, 건식 조립한 건식 조립 과립을 포함하는 것을 특징으로 하는 정제.[One]. (A) a drug selected from ibuprofen, naproxen and ketoprofen, and (B) a disintegrating agent selected from low-substituted hydroxypropylcellulose, carmellose, croscarmellose sodium, crospovidone and carboxymethyl starch sodium. And a dry granulated granule having a mass ratio represented by (B) / (A) of 0.1 to 0.7, (A) component and (B) component mixed at the above ratio and dry granulated.
[2]. (A)성분이, 이부프로펜인 [1] 기재의 정제.[2]. (A) A component as described in [1] whose component is ibuprofen.
[3]. (B)성분이, 저치환도 히드록시프로필셀룰로오스, 카르멜로스 및 크로스카르멜로스나트륨으로부터 선택되는 [1] 또는 [2] 기재의 정제.[3]. (B) The tablet according to [1] or [2], wherein the component is selected from low-substituted hydroxypropyl cellulose, carmelose and croscarmellose sodium.
[4]. 상기 건식 조립 과립 중의 (A)성분과 (B)성분의 합계 함유량이, 40질량% 이상인 [1], [2] 또는 [3] 기재의 정제.[4]. The tablet as described in [1], [2], or [3] whose total content of (A) component and (B) component in the said dry granulated granule is 40 mass% or more.
[5]. 상기 건식 조립 과립의 평균 입경이, 45 내지 900㎛인 것을 특징으로 하는 [1] 내지 [4]의 어느 하나에 기재된 정제.[5]. The tablet according to any one of [1] to [4], wherein an average particle diameter of the dry granulated granules is 45 to 900 µm.
[6]. 상기 건식 조립 과립의 느슨한 부피밀도(loose bulk density)가, 0.3 내지 0.8g/㎤인 것을 특징으로 하는 [1] 내지 [5]의 어느 하나에 기재된 정제.[6]. The loose bulk density of the dry granulated granules is 0.3 to 0.8 g / cm 3, The tablet according to any one of [1] to [5].
본 발명에 의하면, 우수한 붕괴성을 가지며, 게다가 타정시에는 우수한 과립 강도를 나타내고, 붕괴성과 제조성을 양립 가능한, (A) 이부프로펜, 나프록센 및 케토프로펜으로부터 선택되는 특정한 프로피온산계 비스테로이드 항염증제를 함유하는 정제를 제공할 수 있다.According to the present invention, (A) containing a specific propionic acid-based nonsteroidal anti-inflammatory agent selected from ibuprofen, naproxen and ketoprofen, which has excellent disintegration property and shows excellent granular strength at the time of tableting and is compatible with disintegration and manufacturability. Tablets may be provided.
이하, 본 발명에 관해 상세히 설명한다.EMBODIMENT OF THE INVENTION Hereinafter, this invention is demonstrated in detail.
본 발명의 정제는, (A) 이부프로펜, 나프록센 및 케토프로펜으로부터 선택되는 약물과, (B) 저치환도 히드록시프로필셀룰로오스, 카르멜로스, 크로스카르멜로스나트륨, 크로스포비돈 및 카르복시메틸스타치나트륨으로부터 선택되는 붕괴제를 함유하고, (B)/(A)로 표시되는 질량비가 0.1 내지 0.7이고, (A)성분과 (B)성분을 상기 비율로 혼합하고, 건식 조립한 건식 조립 과립을 포함하는 것이다.The tablet of the present invention is prepared from (A) a drug selected from ibuprofen, naproxen and ketoprofen, and (B) low-substituted hydroxypropyl cellulose, carmellose, croscarmellose sodium, crospovidone and carboxymethyl starch sodium. It contains the disintegrating agent selected, The mass ratio represented by (B) / (A) is 0.1-0.7, The dry granulated granules which mixed (A) component and (B) component in the said ratio, and were dry granulated will be.
이하, (I) 건식 조립 과립, (Ⅱ) 건식 조립 과립의 제조 방법, (Ⅲ) 정제, (Ⅳ) 정제의 제조 방법의 순서로 설명한다.Hereinafter, it demonstrates in order of the manufacturing method of (I) dry granulation granules, (II) dry granulation granules, (III) tablet, and (IV) tablet manufacturing method.
(I) 건식 조립 과립(I) dry granulated granules
(A) 이부프로펜, 나프록센 및 케토프로펜으로부터 선택되는 약물과, (B) 저치환도 히드록시프로필셀룰로오스, 카르멜로스, 크로스카르멜로스나트륨, 크로스포비돈 및 카르복시메틸스타치나트륨으로부터 선택되는 붕괴제를 함유하고, (B)/(A)로 표시되는 질량비가 0.1 내지 0.7이고, (A)성분과 (B)성분을 상기 비율로 혼합하고, 건식 조립한 것이다.(A) a drug selected from ibuprofen, naproxen and ketoprofen, and (B) a disintegrating agent selected from low-substituted hydroxypropylcellulose, carmellose, croscarmellose sodium, crospovidone and carboxymethyl starch sodium. And the mass ratio represented by (B) / (A) is 0.1-0.7, (A) component and (B) component are mixed at the said ratio, and are dry granulated.
(A) 이부프로펜, 나프록센 및 케토프로펜으로부터 선택되는 약물(A) a drug selected from ibuprofen, naproxen and ketoprofen
이부프로펜, 나프록센 및 케토프로펜은, 프로피온산계 비스테로이드 항염증제이고, 우수한 소염, 진통, 해열 작용을 갖는 것이다. 이 중에서도, 이부프로펜이 바람직하다. 이들은 1종 단독으로 또는 2종 이상을 적절히 조합시켜서 사용할 수 있다.Ibuprofen, naproxen and ketoprofen are propionic acid nonsteroidal anti-inflammatory agents and have excellent anti-inflammatory, analgesic and antipyretic effects. Among these, ibuprofen is preferable. These can be used individually by 1 type or in combination of 2 or more types.
(B) 저치환도 히드록시프로필셀룰로오스, 카르멜로스, 크로스카르멜로스나트륨, 크로스포비돈 및 카르복시메틸스타치나트륨으로부터 선택되는 붕괴제(B) a disintegrant selected from low-substituted hydroxypropyl cellulose, carmellose, croscarmellose sodium, crospovidone and carboxymethyl starch sodium
이 중에서도, 목적으로 하는 효과의 점에서, 저치환도 히드록시프로필셀룰로오스, 카르멜로스, 크로스카르멜로스나트륨이 바람직하다. 이들은 1종 단독으로 또는 2종 이상을 적절히 조합시켜서 사용할 수 있다.Among these, low substitution hydroxypropyl cellulose, carmellose, and croscarmellose sodium are preferable at the point of the target effect. These can be used individually by 1 type or in combination of 2 or more types.
건식 조립 과립 중의 (B)/(A)로 표시되는, (A)성분에 대한 (B)성분의 함유 질량비는, 0.1 내지 0.7이고, 0.2 내지 0.7이 바람직하고, 0.3 내지 0.7이 보다 바람직하다. (B)/(A)가 0.7을 초과하면, 붕괴성이 역으로 약간 저하되는데다가, 분체가 부피가 커져서 제조가 곤란해진다.The content mass ratio of (B) component with respect to (A) component represented by (B) / (A) in dry granulated granules is 0.1-0.7, 0.2-0.7 are preferable and 0.3-0.7 are more preferable. If (B) / (A) exceeds 0.7, the disintegration property is slightly lowered inversely, and the powder becomes bulky, making production difficult.
건식 조립 과립 중의 (A)성분과 (B)성분의 합계 함유량은, 상기 과립 중의 유효 성분인 (A)성분 농도(AI)의 점에서 높은 쪽이 바람직하다. 구체적으로는, 40질량% 이상이 바람직하고, 50질량% 이상이 보다 바람직하다. 상한은 특별한 제한 없이, 100질량%라도 좋다. 건식 조립 과립 중에 (A)성분, (B)성분 이외의 성분을 고비율로 배합하는 경우, 배합 성분의 종류에 의해서는, 붕괴가 극단적으로 지연되는 경우가 있다. 특히, 히드록시프로필셀룰로오스, 폴리비닐피롤리돈, 히드록시프로필메틸셀룰로오스 등의 수용성 결합제 등을 고비율(10질량% 이상)로 배합하는 경우, 특히 강한 전단력으로 혼합한 경우에는, 붕괴성이 극단적으로 지연되기 때문에, 이들은 건식 조립 과립 중 10질량% 미만 또는 무배합으로 하는 것이 바람직하다.It is preferable that the total content of (A) component and (B) component in dry granulated granules is higher from the point of (A) component concentration (AI) which is an active ingredient in the said granule. 40 mass% or more is specifically, preferable, and 50 mass% or more is more preferable. The upper limit may be 100 mass% without particular limitation. When mix | blending components other than (A) component and (B) component in dry granulation granules at high ratio, disintegration may be extremely retarded depending on the kind of compounding component. In particular, when water-soluble binders such as hydroxypropyl cellulose, polyvinylpyrrolidone, and hydroxypropyl methyl cellulose and the like are mixed at a high ratio (10 mass% or more), especially when mixed with a strong shearing force, disintegration is extremely extreme. Since it is delayed by, it is preferable to make these into less than 10 mass% or no blend in dry granulated granules.
건식 조립 과립에는, 상기 (A)성분과 (B)성분 외에, 본 발명의 효과를 손상시키지 않는 범위, 정제의 물성 및 보존 안정성을 손상시키지 않는 범위에서, 그 밖의 생리활성 성분이나 첨가제를 1종 단독으로 또는 2종 이상을 적절히 조합시켜서, 적량 배합하여도 좋다.In the dry granulated granules, in addition to the components (A) and (B), one other bioactive component or additive may be used in a range that does not impair the effects of the present invention and does not impair the physical properties and storage stability of the tablet. You may mix it suitably individually or in combination of 2 or more types.
생리활성(生理活性) 성분으로서는, 예를 들면, (A)성분 이외의 해열 진통 성분(예를 들면, 피록시캄, 멜록시캄, 암피록시캄, 셀로콕시브, 로페콕시브, 티아라미드, 아세트아미노펜, 메텐자미드, 술피린 등), 진정 최면 성분(예를 들면, 알릴이소프로필아세틸 요소, 브롬발레릴 요소 등), 항히스타민 성분(예를 들면, 염산 이소티펜딜, 염산 디페닐피랄린, 염산 디펜히드라민, 염산 디페테롤 염산 트리프롤리딘, 염산 트리펠레나민, 염산 톤질아민, 염산 페네타진, 염산 메트딜라진, 살리실산 디펜히드라민, 디페닐디술폰산 카르비녹사민, 주석산 알리메마진, 탄닌산 디펜히드라민, 테오쿨산 디페닐피랄린, 나파디실산 메브히드롤린, 프로메타진메틸렌2살리실산염, 말레인산 카르비녹사민, dl-말레인산 클로르페니라민, d-말레인산 클로르페니라민, 인산 디페테롤), 중추 흥분 성분(예를 들면, 안식향산 나트륨카페인, 카페인, 무수 카페인 등), 진해 거담 성분(코데인 인산염, 덱스트로메토르판 취화수소산염, 디메모르판 인산염, 티페피딘히벤즈산염, 메톡시페나민 염산염, 트리메토퀴놀 염산염, 카르보시스테인, 아세틸시스테인, 에틸시스테인, dl-메틸에페드린, 브롬헥신 염산염, 세라펩타제, 염화 리소자임, 암브록솔, 테오필린, 아미노피린), 제산제(건조 수산화 알루미늄 겔, 알루미늄글리시네이트), 비타민 성분(예를 들면, 비타민B1 및 그 유도체 및 그들의 염류, 비타민B2 및 그 유도체 및 그들의 염류, 비타민C 및 그 유도체 및 그들의 염류, 헤스페리딘 및 그 유도체 및 그들의 염류 등) 등을 들 수 있다. 이들의 약효 성분은, 1종 단독으로 또는 2종 이상을 적절히 조합시켜서 사용할 수 있다.As a physiologically active component, for example, antipyretic analgesic components other than (A) component (for example, pyroxycamp, meloxycam, ampicoxycam, cellocoxib, rofecoxib, tiaramid, Acetaminophen, methenezamide, sulfirin, etc.), soothing hypnotic components (e.g., allylisopropylacetyl urea, bromberyl urea, etc.), antihistamine components (e.g. isotifendil hydrochloride, diphenylpyral hydrochloride) , Diphenhydramine hydrochloride, difeterol hydrochloride triprolidine hydrochloride, tripelenamine hydrochloride, tonalamine hydrochloride, penetazine hydrochloride, metdilazine hydrochloride, diphenhydramine salicylic acid diphenhydramine, carbinoxamine amine, tartaric acid alimazine , Diphenhydramine tantanate, diphenylpyraline theoic acid, nahydric acid mebhydroline, promethazinemethylene disalicylate, maleic acid carbinoxamine, dl-maleic acid chlorpheniramine, d-maleic acid chlorpheniramine, difeteate phosphate ), Central excitatory constituents (e.g. sodium benzoate, caffeine, caffeine anhydride, etc.), antitussive expectorant constituents (codeine phosphate, dextromethorphan hydrochloride, dimemorphan phosphate, tifepidine benzate, methoxy Phenamine hydrochloride, trimethoquinol hydrochloride, carbocysteine, acetylcysteine, ethylcysteine, dl-methylephedrine, brohexine hydrochloride, cerapeptase, lysozyme chloride, ambroxol, theophylline, aminopyrin), antacid (dry aluminum hydroxide gel , Aluminum glycinate), vitamin components (for example, vitamin B 1 and its derivatives and salts thereof, vitamin B 2 and its derivatives and salts thereof, vitamin C and its derivatives and salts thereof, hesperidin and its derivatives and salts thereof Etc.) can be mentioned. These drug active ingredients can be used individually by 1 type or in combination of 2 or more types.
첨가제로서는, 예를 들면, 결합제, 부형제, 활택제, 항료, 색소, 감미제, 산미료 등을 들 수 있다. 구체적으로는, 결합제로서는, 전분, α화 전분, 자당, 젤라틴, 아라비아고무 분말, 메틸셀룰로오스, 풀룰란, 덱스트린, 히드록시프로필셀룰로오스(단, 건식 과립 중에 10질량% 미만) 등을 들 수 있다. 부형제로서는, 젖당, 콘스타치, 결정 셀룰로오스(세오라스 등), 분당(粉糖), 만니톨, 경질 무수규산, L-시스테인 등을 사용할 수 있다. 활택제로서는, 스테아린산 마그네슘, 스테아린산 칼슘, 푸마르산 스테아릴나트륨, 경질 무수규산, 폴리에틸렌글리콜, 활석, 스테아린산, 자당지방산 에스테르 등을 들 수 있다. 항료로서는, 멘톨, 리모넨, 식물 정유(박하유, 민트유, 라이치유, 오렌지유, 레몬유 등) 등을 들 수 있다. 감미제로서는, 사카린나트륨, 아스파르탐, 스테비아, 글리시리진산 2칼륨, 아세슬팜칼륨, 타우마틴, 수크랄로스 등을 들 수 있다. 산미료로서는, 구연산, 주석산, 사과산, 호박산, 푸마르산, 젖산 또는 그들의 염 등을 사용할 수 있다. 그 중에서도 자당 지방산 에스테르가 바람직하다.As an additive, a binder, an excipient, a lubricant, a coloring agent, a pigment, a sweetener, an acidulant, etc. are mentioned, for example. Specific examples of the binder include starch, alpha starch, sucrose, gelatin, gum arabic powder, methyl cellulose, pullulan, dextrin, hydroxypropyl cellulose (but less than 10% by mass in dry granules). As the excipient, lactose, corn starch, crystalline cellulose (Seoras, etc.), powdered sugar, mannitol, hard silicic anhydride, L-cysteine and the like can be used. Examples of the lubricant include magnesium stearate, calcium stearate, sodium stearyl fumarate, hard silicic anhydride, polyethylene glycol, talc, stearic acid and sucrose fatty acid ester. Menthol, limonene, vegetable essential oil (mint oil, mint oil, lychee oil, orange oil, lemon oil, etc.) etc. are mentioned as a chemical. Examples of the sweetening agent include sodium saccharin, aspartame, stevia, dipotassium glycyrrhinate, acesulfame potassium, taumartin, sucralose and the like. As the acidulant, citric acid, tartaric acid, malic acid, succinic acid, fumaric acid, lactic acid or salts thereof can be used. Especially, sucrose fatty acid ester is preferable.
건식 조립 과립의 평균 입경은 제조성에 문제가 없는 범위에서 임의로 설정할 수 있지만, 45 내지 900㎛가 바람직하고, 74 내지 700㎛가 보다 바람직하고, 95 내지 550㎛가 더욱 바람직하다. 건식 조립 과립의 입경이 45㎛ 미만이면, (A)성분의 종류에 의해서는 타정시에 충전 불량이나 부착 등의 장해가 생기는 경우가 있다. 또한, 본 발명의 평균 입경은, 개수평균(個數平均) 지름을 의미하고, 레이저 회절식 입자 분포 측정 장치(예를 들면 BECKMAN COULTER사 제 LS13 320)를 사용하여 개수%(미디언 지름)에 의해 산출할 수 있다.Although the average particle diameter of dry granulated granules can be arbitrarily set in the range which does not have a problem in manufacturability, 45-900 micrometers is preferable, 74-700 micrometers is more preferable, 95-550 micrometers is still more preferable. If the particle size of dry granulated granules is less than 45 micrometers, the kind of (A) component may produce the impairment of a filling, adhesion, etc. at the time of tableting. In addition, the average particle diameter of this invention means the number average diameter, and it uses the laser diffraction type particle | grain distribution measuring apparatus (for example, LS13 320 by BECKMAN COULTER company) to number% (median diameter). It can calculate by
상기 건식 조립 과립의 느슨한 부피밀도는 제조성에 문제가 없는 범위에서 임의로 설정할 수 있지만, 0.3 내지 0.8g/㎤가 바람직하고, 0.43 내지 0.71g/㎤가 보다 바람직하고, 0.5 내지 0.7g/㎤가 더욱 바람직하다. 느슨한 부피밀도가 너무 높으면, 과립 내 공극률이 현저하게 저하되고, 과립 내에 물이 침투하기 어려워지고, 신속한 붕괴성이 불충분하게 될 우려가 있다. 한편, 부피밀도가 너무 낮아지면, 과립의 입경이 너무 작아지기 때문에, 정제로 한 때 정제 내의 공극률이 저하되고, 신속한 붕괴성이 불충분하게 될 우려가 있다. 또한, 느슨한 부피밀도는, 피검 분체를 100㎖의 용기에 태핑하지 않고서 충전한 때의 중량 변화(태핑하지 않고서 분체를 충전한 때의 용기의 중량 - 빈 용기의 중량)(g)를, 용기의 체적으로 나눈 값으로서 산출하였다. 측정은 3회 행하고, 그 평균치를 그 과립의 느슨한 부피밀도로 하였다.The loose bulk density of the dry granulated granules may be arbitrarily set within a range without problems in manufacturability, but 0.3 to 0.8 g / cm 3 is preferable, 0.43 to 0.71 g / cm 3 is more preferable, and 0.5 to 0.7 g / cm 3 further desirable. If the loose bulk density is too high, there is a fear that the porosity in the granules is remarkably lowered, water is difficult to penetrate into the granules, and rapid disintegration is insufficient. On the other hand, if the bulk density becomes too low, the particle size of the granules becomes too small, and when tablets are used, the porosity in the tablets decreases, and there is a fear that rapid disintegration is insufficient. In addition, the loose bulk density indicates the weight change (weight of the container at the time of filling the powder without tapping-the weight of the empty container) (g) when the test powder is filled without tapping the 100 ml container. It calculated as the value divided by the volume. The measurement was performed three times, and the average value was made into the loose bulk density of the granules.
(Ⅱ) 건식 조립 과립의 제조 방법(II) Method of producing dry granulated granules
건식 조립 과립은, (A)성분과, (B)성분과, 임의 성분을 혼합하고, 예를 들면, 롤러 콤팩터 등의 압축 조립 기등으로, 롤러 압축함에 의해 제조할 수 있다. 롤 압력은 적절히 선정되지만, 3 내지 11MPa가 바람직하고, 분체 공급 스크루 회전 속도는 1 내지 7rpm의 범위가 바람직하다. 롤 압력을 조정함으로써, 목적으로 하는 느슨한 부피밀도의 것을 얻을 수 있다. 상기 롤러 압축에 의해 얻어진 플레이크를, 해쇄?정립기 등을 사용하여, 해쇄(解碎)?정립(整粒)하고, 목적으로 하는 평균 입경의 것을 얻을 수 있다.Dry granulated granules can be manufactured by mixing (A) component, (B) component, and arbitrary components, for example, by roller compaction by compression granulators, such as a roller compactor. Although a roll pressure is suitably selected, 3-11 Mpa is preferable, and the powder supply screw rotation speed has the preferable range of 1-7 rpm. By adjusting roll pressure, the thing of the loose bulk density of the objective can be obtained. The flake obtained by the said roller compression is pulverized and grained using a crushing-crusher, etc., and the thing of the target average particle diameter can be obtained.
(Ⅲ) 정제(III) tablet
본 발명의 정제는 상기 건식 조립 과립을 포함하는 것이다. 건식 조립 과립의 함유량은, 정제 1정 중 5 내지 95질량%가 바람직하고, 30 내지 70질량%가 더 바람직하다. 정제로서는, 단일의 층으로 이루어지는 단층정이라도 좋고, 복수의 층이 적층된 다층정이라도 좋지만, 붕괴성, 제조의 용이성 등 때문에 단층정인 것이 바람직하다.The tablet of the present invention comprises the dry granulated granules. 5-95 mass% is preferable in one tablet, and, as for content of dry granulated granules, 30-70 mass% is more preferable. As tablets, single-layered crystals composed of a single layer may be used, or multilayered tablets in which a plurality of layers are laminated may be used. However, single-layered crystals are preferable because of disintegration, ease of manufacture and the like.
정제 1정 중의 (A)성분의 비율은 제조성에 문제가 없는 범위에서 임의로 설정할 수 있지만, 붕괴성 및 제조성의 관점에서, 10 내지 90질량%의 범위가 바람직하고, 10 내지 60질량%가 더 바람직하고, 10 내지 40질량%가 더욱 바람직하다. 1정 중의 (A)성분의 비율이 10질량% 미만이면, 정제의 붕괴성은 우수한 것이지만, 정제가 대형화하여 복용에 곤란을 초래하게 된다. 또한, 1정 중의 (A)성분의 비율이 너무 높으면, (A)성분의 종류에 의해서는 부착 등의 타정 장해가 생기는 일이 있다.Although the ratio of (A) component in 1 tablet of tablets can be arbitrarily set in the range which does not have a problem in manufacturability, the range of 10-90 mass% is preferable from a viewpoint of disintegration and manufacturability, and 10-60 mass% is more preferable. And 10-40 mass% is more preferable. If the ratio of the component (A) in one tablet is less than 10% by mass, the disintegration property of the tablet is excellent, but the tablet becomes larger and causes difficulty in taking. Moreover, when the ratio of (A) component in one tablet is too high, tableting disorders, such as adhesion, may arise with the kind of (A) component.
정제의 치수는 특별히 한정되지 않고, (A)성분의 함유량 및 용량 등을 고려하여 적절히 결정할 수 있지만, 정제의 취급하기 쉬움이나 삼킴성의 관점에서, 정제의 지름으로서 5 내지 14㎜φ가 바람직하고, 7 내지 12㎜φ가 보다 바람직하다. 또한, 1정당의 정제 질량으로서는 150 내지 700㎎ 정도가 적절하다.The size of the tablet is not particularly limited, and may be appropriately determined in consideration of the content and capacity of the component (A), but from the viewpoint of ease of handling and swallowability of the tablet, 5 to 14 mmφ is preferable as the diameter of the tablet, 7-12 mm (phi) is more preferable. In addition, as a tablet mass per tablet, about 150-700 mg is suitable.
정제 중에는, 상기 건식 조립 과립에서 예시한, 생리활성 성분이나 첨가제를, 본 발명의 효과를 손상시키지 않는 범위, 정제의 물성 및 보존 안정성을 손상시키지 않는 범위에서, 1종 단독으로 또는 2종 이상을 적절히 조합시켜서, 적량 배합하여도 좋다. 예를 들면, 부형제를 배합하는 경우, 정제 중 10 내지 80질량%, 바람직하게는 30 내지 70질량%이다. 활택제를 배합하는 경우, 정제 중 0.01 내지 5질량%, 바람직하게는 0.1 내지 3질량%이다. 또한, 저치환도 히드록시프로필셀룰로오스, 카르멜로스, 크로스카르멜로스나트륨, 크로스포비돈, 카르복시메틸스타치나트륨 등의 붕괴제를, 본 발명의 과립 성분((B) 성분)과는 별도로 정제에 배합하여도 좋다. 붕괴제를 배합하는 경우는, 정제 중 0.1 내지 30질량%, 바람직하게는 1 내지 10질량%이다.In tablets, one or two or more of the bioactive components and additives exemplified in the dry granulated granules may be used alone or in a range that does not impair the effects of the present invention and that does not impair the physical properties and storage stability of the tablet. You may combine suitably and mix suitably. For example, when mix | blending an excipient, it is 10-80 mass% in tablet, Preferably it is 30-70 mass%. When mix | blending a lubricant, it is 0.01-5 mass% in tablets, Preferably it is 0.1-3 mass%. In addition, disintegrating agents such as low-substituted hydroxypropyl cellulose, carmellose, croscarmellose sodium, crospovidone, and carboxymethyl starch sodium, may be blended in a tablet separately from the granulation component ((B) component) of the present invention. Also good. When mix | blending a disintegrating agent, it is 0.1-30 mass% in tablet, Preferably it is 1-10 mass%.
또한, 정제는, 필요에 따라 코팅제에 의해 코팅 처리를 시행하여도 좋다. 이들의 코팅제로서는, 본 발명이 목적으로 하는 붕괴성을 현저하게 손상시키지 않는 것을 선택하는 것이 바람직하고, 그 중에서도, 수용성 고분자 화합물, 가소제가 바람직하다. 구체적으로는, 수용성 고분자 화합물로서는, 카르멜로스, 히드록시프로필셀룰로오스, 히드록시프로필메틸셀룰로오스, 저치환도 히드록시프로필셀룰로오스, 히드록시메틸셀룰로오스, 메틸셀룰로오스, 에틸셀룰로오스 등의 셀룰로오스류; 아라비아고무, 카르복시비닐 폴리머, 포비돈, 크로스포비돈, 폴리비닐알코올, 폴리아크릴산, 단당류, 2당류 이상의 다당류(설탕(그래뉴당 등)), 젖당, 맥아당, 크실로오스, 이성화 젖당 등), 당알코올(팔라티닛, 소르비톨, 락티톨, 에리트리톨, 크실리톨, 환원전분당화물, 말티톨, 만니톨), 물엿, 이성화(異性化) 당류, 올리고당, 수크로스, 트레할로스, 환원전분당화물(환원전분 분해물) 등을 들 수 있다. 가소제로서는, 구연산 트리에틸, 트리아세틴 등의 일본약국방(일본 히로카와 서점) 및 의약품 첨가물 규격(일본 (주)약사일보사) 등의 공정서(公定書)에 기재되어 있는 것을 들 수 있다. 이들은 1종 단독으로 또는 2종 이상을 적절히 조합시켜서 사용할 수 있다. 코팅제의 사용량은, 정제 전체에 대해 0.5 내지 1. 5질량% 정도로 하면 좋다.In addition, the tablet may be subjected to a coating treatment with a coating agent as necessary. As these coating agents, it is preferable to select those which do not significantly impair the disintegrability aimed at by the present invention, and among these, water-soluble high molecular compounds and plasticizers are preferable. Specific examples of the water-soluble high molecular compound include celluloses such as carmellose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, low-substituted hydroxypropyl cellulose, hydroxymethyl cellulose, methyl cellulose and ethyl cellulose; Gum arabic, carboxyvinyl polymer, povidone, crospovidone, polyvinyl alcohol, polyacrylic acid, monosaccharides, disaccharides or more polysaccharides (sugars, etc.), lactose, maltose, xylose, isomerized lactose Palatine, sorbitol, lactitol, erythritol, xylitol, reduced starch sugars, maltitol, mannitol), starch syrup, isomerized sugars, oligosaccharides, sucrose, trehalose, reduced starch sugars (reduced starch decomposition products) Etc. can be mentioned. Examples of the plasticizer include those described in the Japanese Pharmacopoeia Defense (Japanese Hirokawa Bookstore) such as triethyl citrate and triacetin and the pharmaceutical additive standards (Pharmaceutical Company, Japan). These can be used individually by 1 type or in combination of 2 or more types. What is necessary is just to use the coating agent about 0.5-1.5 mass% with respect to the whole tablet.
본 발명의 정제는, 해열 진통약이나 감기약으로서 사용할 수 있고, 마시기 쉬움, 유효성 발휘의 점에서, 위 중에서 붕괴하는 위 내 붕괴성 정제인 것이 바람직하다.The tablet of the present invention can be used as an antipyretic analgesic drug or a cold medicine, and in view of ease of drinking and effect display, it is preferable that the tablet be disintegratable in the stomach.
(Ⅳ) 정제의 제조 방법(IV) Manufacturing method of tablet
본 발명의 정제는, 건식 조립 과립과 과립 외 첨가물(임의 성분)을 혼합하고, 타정 함에 의해 얻을 수 있다. 혼합은, 보올레 믹서, 더블콘 믹서, V형 믹서, 컨테이너 블렌더 등의 공지의 혼합기를 이용하여 행할 수 있다.The tablet of this invention can be obtained by mixing dry granulated granules and the non-granular additive (optional component), and tableting. Mixing can be performed using well-known mixers, such as a bolore mixer, a double cone mixer, a V-type mixer, and a container blender.
단층정의 정제의 경우, 건식 조립 과립과 과립 외 첨가물(임의 성분)을 혼합하고, 얻어진 혼합물을 타정함에 의해 단층정의 정제를 조제할 수 있다. 타정은 공지의 타정 성형기, 예를 들면 LIBRA(제품명, 일본 (주)기쿠스이제작소 제), HP-AP-MS형(제품명, 일본 (주)전철공소 제) 등의 로터리식의 타정 성형기 등을 이용할 수 있다. 타정압은, 정제의 인장 강도가 75 내지 250N/㎠가 되도록 조정하면 좋다.In the case of the tablet of a monolayer tablet, the tablet of a monolayer tablet can be prepared by mixing dry granulated granules and the non-granular additive (optional component), and tableting the obtained mixture. The tableting may be a well-known tablet forming machine, for example, a rotary tableting machine such as LIBRA (product name, manufactured by Kikusui Co., Ltd.) and HP-AP-MS type (product name, manufactured by Japan Electric Railway Corporation). It is available. A tableting pressure may be adjusted so that the tensile strength of a tablet may be 75-250 N / cm <2>.
다층정의 정제인 경우, 건식 조립 과립 및 과립 외 첨가물의 어느 한쪽을 제 1층에 배합하고, 다른쪽을 제 2층에 배합할 수 있지만, 과립 외 첨가물을 제 1층으로 하고, 그 위에 건식 조립 과립을 제 2층으로서 적층한 후, 상저(上杵)와 하저(下杵)의 사이에서 압축 성형한 것이 바람직하다.In the case of multi-layer tablets, dry granulated granules and one of the non-granular additives may be blended into the first layer and the other may be blended into the second layer, but the non-granular additives may be the first layer and dry granulated thereon. It is preferable to laminate | stack granules as a 2nd layer, and to carry out compression molding between the upper and lower bottoms.
[실시예][Example]
이하, 실시예 및 비교예를 나타내어, 본 발명을 구체적으로 설명하지만, 본 발명은 하기한 실시예로 제한되는 것은 아니다. 또한, 하기한 예에서 특별한 명기가 없는 경우는, 표 중의 각 성분의 양은 순분 환산한 양이고, (%)는 질량%, 비율은 질량비이다.Hereinafter, although an Example and a comparative example are shown and this invention is demonstrated concretely, this invention is not limited to the following Example. In addition, in the following example, when there is no special specification, the quantity of each component in a table | surface is the quantity converted into pure parts, (%) is the mass%, and a ratio is the mass ratio.
[실시예 1 내지 8][Examples 1 to 8]
(A) 약물과 (B) 붕괴제를 혼합한 후, 압축 조립기(롤러 콤팩터 : 일본 TURBO공업사 제)를 이용하여, 롤 압력은 7.0MPa, 분체 공급 스크루 회전 속도 3.0rpm의 조건으로 롤러 압축하였다. 롤러 압축에 의해 얻어진 플레이크를 해쇄?정립기(피오레: 일본 도쿠주공작소사 제)로 해쇄?정립하여, 건식 조립 과립을 얻었다. 실시예에서 얻어진 건식 조립 과립의 평균 입경은 모두 95 내지 550㎛, 느슨한 부피밀도는 0.5 내지 0.7g/㎤이다.After mixing (A) drug and (B) disintegrating agent, the roller pressure was roller-compressed using a compression granulator (Roller Compactor: manufactured by TURBO Industries, Ltd.) under the conditions of 7.0 MPa and a powder feed screw rotation speed of 3.0 rpm. . The flakes obtained by roller compacting were pulverized and granulated by a crushing and sizing machine (Fiore: manufactured by Tokuju Kogyo Co., Ltd.) to obtain dry granulated granules. The average particle diameter of the dry granulated granules obtained in the examples was 95 to 550 µm, and the loose bulk density was 0.5 to 0.7 g / cm 3.
얻어진 건식 압축 조립 과립과, 표 중의 과립 외 첨가물(스테아린산 마그네슘을 제외한다)을 혼합기(보올레 컨테이너 믹서: 일본 코토부키 기연공업사 제)로 20분간 혼합하였다. 혼합 후, 스테아린산 마그네슘을 첨가하고, 다시 10분간 혼합하여, 타정용 과립으로 하였다.The dry compressed granulated granules obtained and the non-granular additives (excluding magnesium stearate) in the table were mixed for 20 minutes by a mixer (boole container mixer: manufactured by Kotobuki Co., Ltd.). After mixing, magnesium stearate was added and mixed again for 10 minutes to obtain a granulation tablet.
이 타정용 과립을, 타정기(일본 기쿠스이제작소 제 : 리부라)를 이용하여 타정하였다. 정제 지름은 φ9.0㎜로 하고, 정제의 인장 강도는 200N/㎠가 되도록 타정압을 조정하였다. 얻어진 정제에 대해 붕괴 시험을 행하여, 붕괴성을 평가하였다. 또한, 실시 예의 정제는 타정기에의 부착이나 정제의 캡핑, 타정 분체의 구(臼) 내에의 충전 불량 등의 장해가 없고, 제조성이 우수한 것이었다.This tableting granules were tableted using a tableting machine (manufactured by Nippon Kikusui Co., Ltd .: Ribura). The tablet diameter was φ9.0 mm, and the tableting pressure was adjusted so that the tablet had a tensile strength of 200 N / cm 2. The disintegration test was done about the obtained tablet and the disintegration property was evaluated. In addition, the tablet of the Example was excellent in manufacturability without obstacles, such as adhesion to a tableting machine, capping of a tablet, and poor filling of the tablet powder.
또한, 건식 조립 과립의 평균 입자는, 레이저 회절식 입자 분포 측정 장치(BECKMAN COULTER사 제 LS13 320)로 측정하고, 개수%에 의해 비율을 산출하였다.In addition, the average particle of the dry granulated granules was measured by the laser diffraction particle | grain distribution measuring apparatus (LS13 320 by BECKMAN COULTER company), and ratio was computed by the number%.
[붕괴 시험][Collapse test]
제15정일본약국방에 수재(收載)된 정제의 붕괴 시험법에 준하여, 6정의 붕괴 시간을 측정하고 그 평균치를 구하였다. 평균치로부터 결과를 하기에 의거하여 나타낸다.The disintegration time of six tablets was measured and the average value was calculated | required according to the disintegration test method of the tablet hand-held by the 15th Japanese Pharmacy. The results are shown based on the following from the average values.
◎ : 붕괴 시간 45초 미만◎: less than 45 seconds decay time
○ : 붕괴 시간 45초 이상 60초 미만○: decay time 45 seconds or less less than 60 seconds
△ : 붕괴 시간 60초 이상 120초 미만(Triangle | delta): More than 60 second of collapse time
× : 붕괴 시간 120초 이상×: decay time 120 seconds or more
상기 실시예로부터 분명한 바와 같이, (A)성분과 (B)성분을 건식 조립하여 얻은 과립을 사용한 정제는 우수한 붕괴성을 나타내었다. 특히 (A)성분으로서 이부프로펜을 사용한 때에 양호한 붕괴성을 나타내었다. 또한 (B)성분으로서 저치환도 히드록시프로필셀룰로오스, 카르멜로스, 크로스카르멜로스나트륨을 사용한 때에도 우수한 붕괴성을 나타내었다. 이들 중에서도, 저치환도 히드록시프로필셀룰로오스, 카르멜로스를 사용한 때의 붕괴성이 보다 우수하고, 저치환도 히드록시프로필셀룰로오스를 사용한 때가 가장 붕괴성이 우수하였다. 또한 실시예 8에 표시한 바와 같이, (A), (B)성분 이외에 히드록시프로필셀룰로오스를 첨가제로서 공(共)배합한 건식 조립 과립에서도 우수한 붕괴성을 나타내었다.As is apparent from the above examples, tablets using granules obtained by dry granulating the component (A) and the component (B) showed excellent disintegration properties. In particular, when ibuprofen was used as (A) component, favorable disintegration was shown. Also, when the low-substituted hydroxypropyl cellulose, carmellose and croscarmellose sodium were used as the component (B), excellent disintegration property was also shown. Among these, the disintegration property at the time of using low-substituted hydroxypropyl cellulose and carmellose was more excellent, and the low substitution degree was the most excellent at the time of using hydroxypropyl cellulose. Moreover, as shown in Example 8, the excellent granulated granules which co-blended hydroxypropyl cellulose as an additive other than (A) and (B) component showed the outstanding disintegration property.
[비교예 1]Comparative Example 1
(A) 약물로서 이부프로펜을 선택하고, (B) 붕괴제와의 혼합 분체를 조제한 후, 히드록시프로필셀룰로오스 수용액을 사용하여, (A) 및 (B) 혼합 분체를 습식 교반 조립하였다. 건조 후, 이 조립 과립을 해쇄?정립기(피오레: 일본 도쿠주공작소사 제)로 해쇄?정립하여, 과립을 얻었다. 얻어진 과립과, 표 중의 과립 외 첨가물(스테아린산 마그네슘을 제외한다)을 혼합기(보올레 컨테이너 믹서: 일본 코토부키 기연공업사 제)로 20분간 혼합하였다. 혼합 후, 스테아린산 마그네슘을 첨가하고, 다시 10분간 혼합하여, 타정용 과립으로 하였다.(A) Ibuprofen was selected as a drug, (B) the mixed powder with a disintegrating agent was prepared, and (A) and (B) mixed powder were wet-stirred and granulated using the aqueous solution of hydroxypropyl cellulose. After drying, the granulated granules were disintegrated and granulated with a crushing and sizing machine (Fiore: manufactured by Tokuju Kogyo Co., Ltd.) to obtain granules. The obtained granules and the extragranular additives (except magnesium stearate) in the table were mixed for 20 minutes by a mixer (boole container mixer: manufactured by Kotobuki Co., Ltd.). After mixing, magnesium stearate was added and mixed again for 10 minutes to obtain a granulation tablet.
이 타정용 과립을, 타정기(일본 기쿠스이제작소 제: 리부라)를 이용하여 타정하였다. 정제 지름은 φ9.0㎜로 하고, 정제의 인장 강도는 200N/㎠가 되도록 타정압을 조정하였다. 얻어진 정제에 대해 붕괴 시험을 행하여, 붕괴성을 평가하였다.The tableting granules were tableted using a tableting machine (manufactured by Nippon Kikusui Co., Ltd .: Ribura). The tablet diameter was φ9.0 mm, and the tableting pressure was adjusted so that the tablet had a tensile strength of 200 N / cm 2. The disintegration test was done about the obtained tablet and the disintegration property was evaluated.
[참고예 1, 2][Reference Examples 1 and 2]
(A) 약물로서 아세트아미노펜, 아스피린을 선택하고, (B) 붕괴제와의 혼합 분체를 조제한 후, 히드록시프로필셀룰로오스 수용액을 사용하여, (A) 및 (B) 혼합 분체를 습식 교반 조립하였다. 건조 후, 이 조립 과립을 해쇄?정립기(피오레: 일본 도쿠주공작소사 제)로 해쇄?정립하여, 과립을 얻었다. 얻어진 과립과, 표 중의 과립 외 첨가물(스테아린산 마그네슘을 제외한다)을 혼합기(보올레 컨테이너 믹서: 일본 코토부키 기연공업사 제)로 20분간 혼합하였다. 혼합 후, 스테아린산 마그네슘을 첨가하고, 다시 10분간 혼합하여, 타정용 과립으로 하였다.(A) Acetaminophen and aspirin were selected as a drug, and (B) mixed powder with a disintegrating agent was prepared, and (A) and (B) mixed powder were wet-stirred and granulated using the aqueous solution of hydroxypropyl cellulose. After drying, the granulated granules were disintegrated and granulated with a crushing and sizing machine (Fiore: manufactured by Tokuju Kogyo Co., Ltd.) to obtain granules. The obtained granules and the extragranular additives (except magnesium stearate) in the table were mixed for 20 minutes by a mixer (boole container mixer: manufactured by Kotobuki Co., Ltd.). After mixing, magnesium stearate was added and mixed again for 10 minutes to obtain a granulation tablet.
이 타정용 과립을, 타정기(일본 기쿠스이제작소 제: 리부라)를 이용하여 타정하였다. 정제 지름은 φ9.0㎜로 하고, 정제의 인장 강도는 200N/㎠가 되도록 타정압을 조정하였다. 얻어진 정제에 대해 붕괴 시험을 행하여, 붕괴성을 평가하였다.The tableting granules were tableted using a tableting machine (manufactured by Nippon Kikusui Co., Ltd .: Ribura). The tablet diameter was φ9.0 mm, and the tableting pressure was adjusted so that the tablet had a tensile strength of 200 N / cm 2. The disintegration test was done about the obtained tablet and the disintegration property was evaluated.
[비교예 2]Comparative Example 2
(A) 약물로서 이부프로펜을 선택하고, (B) 붕괴제와의 혼합 분체를 조제한 후, 정제수를 첨가하고, (A) 및 (B) 혼합 분체를 교반하였다. 건조 후, 이 과립을 해쇄?정립기(피오레: 일본 도쿠주공작소사 제)로 해쇄?정립하였다. 얻어진 과립과, 표 중의 과립 외 첨가물(스테아린산 마그네슘을 제외한다)을 혼합기(보올레 컨테이너 믹서: 일본 코토부키 기연공업사 제)로 20분간 혼합하였다. 혼합 후, 스테아린산 마그네슘을 첨가하고, 다시 10분간 혼합하여, 타정용 과립으로 하였다.(A) Ibuprofen was selected as a drug, (B) mixed powder with a disintegrating agent was prepared, purified water was added, and (A) and (B) mixed powder were stirred. After drying, the granules were crushed and granulated by a crushing and sizing machine (Fiore: manufactured by Tokuju Kogyo Co., Ltd.). The obtained granules and the extragranular additives (except magnesium stearate) in the table were mixed for 20 minutes by a mixer (boole container mixer: manufactured by Kotobuki Co., Ltd.). After mixing, magnesium stearate was added and mixed again for 10 minutes to obtain a granulation tablet.
이 타정용 과립을, 타정기(일본 기쿠스이제작소 제: 리부라)를 이용하여 타정에 제공하였다. 그러나 물만으로 습식 교반 조립을 행한 과립은, 과립 강도가 약하고, 또한 유동성도 불량이고, 정상적으로 타정을 할 수가 없었다.The tableting granules were subjected to tableting using a tableting machine (manufactured by Nippon Kikusui Co., Ltd .: Ribura). However, the granules which wet-granulated only with water had weak granule strength, poor fluidity, and could not be tableted normally.
비교예 1에 나타내는 바와 같이, (A), (B)성분을, 히드록시프로필셀룰로오스 수용액을 사용하여 습식 교반 조립한 경우에는 붕괴성이 현저하게 지연되었다.As shown in the comparative example 1, when wet-stirring granulated (A) and (B) components using the hydroxypropyl cellulose aqueous solution, disintegration remarkably retarded.
참고예 1, 2에 나타내는 바와 같이, (A)성분으로서, (A)성분 이외의 성분(아세트아미노펜, 아스피린)을 사용한 때에는, 습식 교반 조립 과립을 사용한 경우에도 붕괴성이 지연되는 일이 없고, 우수한 붕괴성을 나타내고, 본 발명의 (A)성분에서 보이는 바와 같은 과제는 생기지 않았다. 또한, 수용성 결합제를 사용하지 않고 물만으로 습식 교반 조립을 행한 과립은, 과립 강도가 약하고, 또한 유동성도 불량이고, 정상적으로 타정을 행할 수가 없었다(비교예 2).As shown in Reference Examples 1 and 2, when the components (acetaminophen, aspirin) other than the component (A) were used as the component (A), even when wet agitation granules were used, disintegration was not delayed. Excellent disintegration was shown and the problem as seen with (A) component of this invention did not arise. Moreover, the granules which wet-granulated only with water without using a water-soluble binder had weak granule strength, poor fluidity, and could not be tableted normally (Comparative Example 2).
이상의 것으로부터, 본 발명의 (A)성분의 조립 과립을 포함하는 정제에서는, 우수한 정제 붕괴성을 발휘하는데다가, (A)성분을 건식 조립 과립으로 배합한 것이 매우 유용하다고 말할 수 있다.In view of the above, in the tablet containing granulated granules of the component (A) of the present invention, it can be said that it is very useful to combine the (A) component with the dry granulated granules while exhibiting excellent tablet disintegration properties.
[실시예 9 내지 13][Examples 9 to 13]
(A)성분과 (B)성분의 배합 비율을 바꾸고, 상기 실시예와 같은 방법으로 건식 조립 과립을 얻었다. 얻어진 건식 조립 과립을 표 3에서 표시하는 배합 비율이 되도록 혼합하여, 타정용 과립을 얻었다. 얻어진 타정용 과립을 상기 실시예와 같은 조건으로 타정하여, 정제의 붕괴성을 평가하였다. 또한, 실시 예의 정제는 타정기에의 부착이나 정제의 캡핑, 타정 분체의 구(臼) 내에의 충전 불량 등의 장해가 없고, 제조성이 우수한 것이었다.The compounding ratio of (A) component and (B) component was changed and dry granulated granules were obtained by the method similar to the said Example. The obtained dry granulated granules were mixed so as to have a blending ratio shown in Table 3 to obtain tablet granules. The obtained tableting granules were tableted under the same conditions as in the above examples, and the disintegration properties of the tablets were evaluated. In addition, the tablet of the Example was excellent in manufacturability without obstacles, such as adhesion to a tableting machine, capping of a tablet, and poor filling of the tablet powder.
또한, 실시예 9 내지 13에서의 건식 조립 과립의 평균 입경은 모두 100 내지 550㎛, 느슨한 부피밀도는 0.5 내지 0.7g/㎤이다.In addition, the average particle diameter of the dry granulated granules in Examples 9-13 is 100-550 micrometers, and loose bulk density is 0.5-0.7 g / cm <3>.
실시예 9 내지 13과 같이, (B)/(A)=0.1 내지 0.7의 범위에서 우수한 붕괴성을 나타내었다. (B)/(A)=0.2 이상에서 양호한 붕괴성을 나타내고, (B)/(A)=0.25 이상에서 더욱 양호한 붕괴성을 나타내었다. (B)/(A)=0.7 이상에서는 붕괴성은 양호한 것이지만, 분체가 부피가 커져서, 제조가 곤란해졌다.As in Examples 9 to 13, excellent disintegration was shown in the range of (B) / (A) = 0.1 to 0.7. Good disintegration was shown at (B) / (A) = 0.2 or more, and more excellent disintegration was shown at (B) / (A) = 0.25 or more. In (B) / (A) = 0.7 or more, disintegration is favorable, but powder became large, and manufacture became difficult.
[실시예 14 내지 20][Examples 14 to 20]
건식 조립 과립의 평균 입경, 느슨한 부피밀도를 표 4에 기재한 바와 같이 바꾸고, 과립 외 첨가물과 혼합 후, 타정을 행하여, 정제를 얻었다. 이 정제에 관해 붕괴성을 평가하였다.The average particle diameter and loose bulk density of the dry granulated granules were changed as shown in Table 4, and after mixing with the non-granular additives, they were tableted to obtain tablets. The disintegration was evaluated for this tablet.
건식 조립 과립의 평균 입경이 45 내지 900㎛, 느슨한 부피밀도 0.4 내지 0.7의 범위로 한 정제는, 우수한 붕괴성을 나타내었다. 특히 평균 입경 74 내지 700㎛의 범위에서 보다 우수한 붕괴성을 나타내고, 평균 입경 약 95 내지 500㎛의 범위에서 더욱 우수한 붕괴성을 나타내었다.Tablets in which the dry granulated granules had an average particle diameter of 45 to 900 µm and a loose bulk density of 0.4 to 0.7 exhibited excellent disintegration properties. In particular, it showed better disintegration in the range of an average particle diameter of 74-700 micrometers, and showed further excellent disintegration in the range of an average particle diameter of about 95-500 micrometers.
[실시예 21]Example 21
(A)성분으로서 이부프로펜, (B)성분으로서 저치환도 히드록시프로필셀룰로오스를 선택하고, (A)성분 1500g과 (B)성분 600g과, 기타성분으로서 브롬헥신 염산염 40g을 혼합하고, 이 혼합 분체를 롤러 콤팩터로 롤 압력은 7.0MPa, 분체 공급 스크루 회전 속도 3.0rpm의 조건으로 롤러 압축하였다. 롤러 압축에 의해 얻어진 플레이크를 피오레로 해쇄?정립하여, 건식 조립 과립을 얻었다. 건식 조립 과립 외의 성분으로서, 덱스트로메토르판 취화수소산염 96g, 무수 카페인 150g, 클레마스틴푸마르산염 2.68g, 아스코르빈산 칼슘 200g, 건조 수산화 알루미늄 겔 400g, dl-염산 메틸에페드린 120g, 젖당 조립물 2969.12g, 크로스카르멜로스나트륨 162g을 보올레 컨테이너 믹서로 20분간 혼합하여, 건식 조립 과립 외의 혼합 분체 4099.8g을 얻었다.Choose ibuprofen as (A) component, low-substituted hydroxypropyl cellulose as (B) component, mix 1500 g of (A) components, 600 g of (B) components, and 40 g of brohexine hydrochloride as other components, and mix this powder The roller compactor was roller compacted under the conditions of a roll pressure of 7.0 MPa and a powder feed screw rotation speed of 3.0 rpm. The flakes obtained by roller compacting were pulverized and granulated with Fiore to obtain dry granulated granules. As components other than dry granulated granules, 96 g of dextromethorphan hydrochloride, 150 g of anhydrous caffeine, 2.68 g of clemastine fumarate, 200 g of calcium ascorbate, 400 g of dry aluminum hydroxide gel, 120 g of dl-methyl hydrochloride, lactose granulation 2969.12 g of water and 162 g of croscarmellose sodium were mixed for 20 minutes by a bolore container mixer to obtain 4099.8 g of mixed powder other than dry granulated granules.
이것에 건식 조립 과립 1284g을 가하고, 보올레 컨테이너 믹서로 혼합 후, 스테아린산 마그네슘을 16.2g 첨가하고, 다시 10분간 혼합하고, 표 5에 표시하는 조성의 타정용 분체를 얻었다. 이 타정용 분체를, 타정기(일본 기쿠스이제작소 제: 리부라)를 이용하여 타정하였다. 정제 지름은 φ9.0㎜로 하고, 정제의 인장 강도는 200N/㎠가 되도록 타정압을 조정하였다. 얻어진 정제에 대해 붕괴 시험을 행하여, 붕괴성을 평가하였다.To this, 1284 g of dry granulated granules were added, and after mixing with a boule container mixer, 16.2 g of magnesium stearate was added, mixed for another 10 minutes, and a tableting powder having a composition shown in Table 5 was obtained. This tableting powder was compressed into tablets using a tableting machine (manufactured by Nippon Kikusui Co., Ltd .: Ribura). The tablet diameter was φ9.0 mm, and the tableting pressure was adjusted so that the tablet had a tensile strength of 200 N / cm 2. The disintegration test was done about the obtained tablet and the disintegration property was evaluated.
또한, 실시예 21에서의 건식 조립 과립의 평균 입경은 100 내지 550㎛, 느슨한 부피밀도는 0.5 내지 0.7g/㎤이다.Moreover, the average particle diameter of the dry granulated granules in Example 21 is 100-550 micrometers, and loose bulk density is 0.5-0.7 g / cm <3>.
[실시예 22][Example 22]
(A)성분으로서 이부프로펜, (B)성분으로서 저치환도 히드록시프로필셀룰로오스를 선택하고, (A)성분 3375g과 (B)성분 1350g을 혼합하고, 이 혼합 분체를 롤러 콤팩터로 롤 압력은 7.0MPa, 분체 공급 스크루 회전 속도 3.0rpm의 조건으로 롤러 압축하였다. 롤러 압축에 의해 얻어진 플레이크를 피오레로 해쇄?정립하여, 건식 조립 과립을 얻었다.Selected ibuprofen as (A) component and low-substituted hydroxypropyl cellulose as (B) component, 3375 g of (A) component and 1350 g of (B) component were mixed, and this mixed powder was rolled with a roller compactor in 7.0 The roller was compressed under the conditions of MPa and a powder feed screw rotation speed of 3.0 rpm. The flakes obtained by roller compacting were pulverized and granulated with Fiore to obtain dry granulated granules.
건식 조립 과립 외의 성분으로서 무수 카페인 375g, 건조 수산화 알루미늄 겔 1000g, 젖당 조립물 1442g, 크로스카르멜로스나트륨 30g을 보올레 컨테이너 믹서로 20분간 혼합하여, 건식 조립 과립 외의 혼합 분체 2850g을 얻었다.As components other than the dry granulated granules, 375 g of anhydrous caffeine, 1000 g of dry aluminum hydroxide gel, 1442 g of lactose granulated substance, and 30 g of croscarmellose sodium were mixed for 20 minutes by a bolore container mixer to obtain 2850 g of mixed powder other than the dry granulated granules.
이것에 건식 조립 과립 3150g을 가하고, 보올레 컨테이너 믹서로 혼합 후, 스테아린산 마그네슘을 3g 첨가하고, 다시 10분간 혼합하여, 표 6에 표시하는 조성의 타정용 분체를 얻었다. 이 타정용 분체를, 타정기(일본 기쿠스이제작소 제: 리부라)를 이용하여 타정하였다. 정제 지름은 φ9.0㎜로 하고, 정제의 인장 강도는 200N/㎠가 되도록 타정압을 조정하였다. 얻어진 정제에 대해 붕괴 시험을 행하여, 붕괴성을 평가하였다. To this, 3150 g of dry granulated granules were added, and after mixing with a polley container mixer, 3 g of magnesium stearate was added, followed by further mixing for 10 minutes to obtain a tableting powder having the composition shown in Table 6. This tableting powder was compressed into tablets using a tableting machine (manufactured by Nippon Kikusui Co., Ltd .: Ribura). The tablet diameter was φ9.0 mm, and the tableting pressure was adjusted so that the tablet had a tensile strength of 200 N / cm 2. The disintegration test was done about the obtained tablet and the disintegration property was evaluated.
또한, 실시예 22에서의 건식 조립 과립의 평균 입경은 100 내지 550㎛, 느슨한 부피밀도는 0.5 내지 0.7g/㎤이다.Moreover, the average particle diameter of the dry granulated granules in Example 22 is 100-550 micrometers, and loose bulk density is 0.5-0.7 g / cm <3>.
[실시예 23][Example 23]
(A)성분으로서 이부프로펜, (B)성분으로서 저치환도 히드록시프로필셀룰로오스를 선택하고, (A)성분 2600g과 (B)성분 1000g을 혼합하고, 또한 아세트아미노펜 2600g, 히드록시프로필셀룰로오스 200g, 경질 무수 규산 120g을 혼합하고, 이 혼합 분체를 롤러 콤팩터로 롤 압력은 7.0MPa, 분체 공급 스크루 회전 속도 3.0rpm의 조건으로 롤러 압축하였다. 롤러 압축에 의해 얻어진 플레이크를 피오레로 해쇄?정립하여, 건식 조립 과립을 얻었다.Choose ibuprofen as (A) component and low-substituted hydroxypropyl cellulose as (B) component, mix 2600 g of component (A) and 1000 g of (B) component, and also add 2600 g of acetaminophen, 200 g of hydroxypropyl cellulose, and hard 120 g of silicic anhydrides were mixed, and this mixed powder was roller-compressed with a roller compactor under the conditions of a roll pressure of 7.0 MPa and a powder feed screw rotation speed of 3.0 rpm. The flakes obtained by roller compacting were pulverized and granulated with Fiore to obtain dry granulated granules.
건식 조립 과립 외의 성분으로서 건조 수산화 알루미늄 겔 840g, 결정 셀룰로오스 1200g, 저치환도 히드록시프로필셀룰로오스 180g을 보올레 컨테이너 믹서로 20분간 혼합하여, 건식 조립 과립 외의 혼합 분체 2220g을 얻었다.As components other than the dry granulated granules, 840 g of dry aluminum hydroxide gel, 1200 g of crystalline cellulose, and 180 g of low-substituted hydroxypropyl cellulose were mixed for 20 minutes with a boule container mixer to obtain 2220 g of mixed powders other than the dry granulated granules.
이것에 건식 조립 과립 3858g을 가하고, 보올레 컨테이너 믹서로 혼합 후, 스테아린산 마그네슘을 12g 첨가하고, 다시 10분간 혼합하여, 타정용 분체를 얻었다. 이 타정용 분체를 타정기(일본 기쿠스이제작소 제: 리부라)를 이용하여 타정하였다. 정제 지름은 φ9.0㎜로 하고, 정제의 인장 강도는 200N/㎠가 되도록 타정압을 조정하였다. 얻어진 정제에 대해 붕괴 시험을 행하여, 붕괴성을 평가하였다.To this, 3858 g of dry granulated granules were added, and after mixing with a polley container mixer, 12 g of magnesium stearate was added and mixed for another 10 minutes to obtain a tableting powder. This tableting powder was compressed into tablets using a tableting machine (manufactured by Nippon Kikusui Co., Ltd .: Ribura). The tablet diameter was φ9.0 mm, and the tableting pressure was adjusted so that the tablet had a tensile strength of 200 N / cm 2. The disintegration test was done about the obtained tablet and the disintegration property was evaluated.
또한, 실시예 23에서의 건식 조립 과립의 평균 입경은 100 내지 550㎛, 느슨한 부피밀도는 0.5 내지 0.7이였다.In addition, the average particle diameter of the dry granulated granules in Example 23 was 100 to 550 µm, and the loose bulk density was 0.5 to 0.7.
[실시예 24]Example 24
(A)성분으로서 이부프로펜, (B)성분으로서 저치환도 히드록시프로필셀룰로오스를 선택하고, (A)성분 2600g과 (B)성분 1000g을 혼합하고, 또한 아세트아미노펜 2600g, 자당지방산 에스테르 200g, 카르멜로스1200g을 혼합하고, 이 혼합 분체를 롤러 콤팩터로 롤 압력은 7.0MPa, 분체 공급 스크루 회전 속도 3.0rpm의 조건으로 롤러 압축하였다. 롤러 압축에 의해 얻어진 플레이크를 피오레로 해쇄?정립하여, 건식 조립 과립을 얻었다.Choose ibuprofen as (A) component, and low-substituted hydroxypropyl cellulose as (B) component, mix 2600 g of component (A) and 1000 g of (B) component, and further, 2600 g of acetaminophen, 200 g of sucrose fatty acid ester, carmellose 1200 g was mixed, and this mixed powder was roller-compressed with the roller compactor on condition of 7.0 MPa and the powder feed screw rotation speed of 3.0 rpm. The flakes obtained by roller compacting were pulverized and granulated with Fiore to obtain dry granulated granules.
건식 조립 과립 외의 성분으로서 건조 수산화 알루미늄 겔 840g, 결정 셀룰로오스 1200g, 저치환도 히드록시프로필셀룰로오스 180g을 보올레 컨테이너 믹서로 20분간 혼합하여, 건식 조립 과립 외의 혼합 분체 2220g을 얻었다.As components other than the dry granulated granules, 840 g of dry aluminum hydroxide gel, 1200 g of crystalline cellulose, and 180 g of low-substituted hydroxypropyl cellulose were mixed for 20 minutes with a boule container mixer to obtain 2220 g of mixed powders other than the dry granulated granules.
이것에 건식 조립 과립 4200g을 가하고, 보올레 컨테이너 믹서로 혼합 후, 스테아린산 마그네슘을 12g 첨가하고, 다시 10분간 혼합하여, 타정용 분체를 얻었다. 이 타정용 분체를 타정기(일본 기쿠스이제작소 제: 리부라)를 이용하여 타정하였다. 정제 지름은 φ9.0㎜로 하고, 정제의 인장 강도는 200N/㎠가 되도록 타정압을 조정하였다. 얻어진 정제에 대해 붕괴 시험을 행하여, 붕괴성을 평가하였다.To this, 4200 g of dry granulated granules were added, 12 g of magnesium stearate was added and mixed for 10 minutes, after mixing with a ivory container mixer, to obtain a tableting powder. This tableting powder was compressed into tablets using a tableting machine (manufactured by Nippon Kikusui Co., Ltd .: Ribura). The tablet diameter was φ9.0 mm, and the tableting pressure was adjusted so that the tablet had a tensile strength of 200 N / cm 2. The disintegration test was done about the obtained tablet and the disintegration property was evaluated.
또한, 실시예 24에서의 건식 조립 과립의 평균 입경은 100 내지 550㎛, 느슨한 부피밀도는 0.5 내지 0.7이였다.Moreover, the average particle diameter of the dry granulated granules in Example 24 was 100-550 micrometers, and loose bulk density was 0.5-0.7.
실시예 및 비교예를 조제할 때에 사용한 원료를 이하에 나타낸다.The raw material used when preparing the Example and the comparative example is shown below.
이부프로펜: BASF사 제Ibuprofen: made by BASF
나프록센: TEVA PARMACEUTICAL사 제Naproxen: product made by TEVA PARMACEUTICAL company
아세트아미노펜: 일본 이와끼제약(주) 제Acetaminophen: Japan Iwaki Pharmaceutical Co., Ltd.
무수 카페인: 일본 시라트리 제약(주) 제Anhydrous caffeine: Japan Shiratree Pharmaceutical Co., Ltd.
저치환도 히드록시프로필셀룰로오스: 일본 신에쓰화학공업(주) 제, 상품명 「LH-31」Low-substituted hydroxypropyl cellulose: Shin-Etsu Chemical Co., Ltd. make, brand name "LH-31"
히드록시프로필셀룰로오스: 일본 니혼소다(주) 제, 상품명 「HPC-SSL」Hydroxypropyl cellulose: Nippon Nippon Soda Co., Ltd., brand name "HPC-SSL"
젖당 조립물: 일본 후로인토산업사 제, 상품명 「젖당G」Lactose granulated product: Japanese lactose company, brand name `` Lactose G ''
크로스카르멜로스나트륨: 일본 아사히가세이사 제, 상품명「키코레토ND-2SH」Croscarmellose sodium: product made in Asahi Kasei Co., Ltd., brand name "Kikoretto ND-2SH"
스테아린산 마그네슘: 일본 태평화학산업(주) 제Magnesium stearate: manufactured by Japan Taiping Chemical Industry Co., Ltd.
Claims (6)
(A)성분이, 이부프로펜인 것을 특징으로 하는 정제.The method of claim 1,
(A) A component is ibuprofen, The tablet characterized by the above-mentioned.
(B)성분이, 저치환도 히드록시프로필셀룰로오스, 카르멜로스 및 크로스카르멜로스나트륨으로부터 선택되는 것을 특징으로 하는 정제.3. The method according to claim 1 or 2,
(B) A component characterized by the low substitution hydroxypropyl cellulose, carmellose, and croscarmellose sodium.
상기 건식 조립 과립 중의 (A)성분과 (B)성분의 합계 함유량이, 40질량% 이상인 것을 특징으로 하는 정제.3. The method according to claim 1 or 2,
The total content of (A) component and (B) component in the said dry granulated granules is 40 mass% or more, The tablet characterized by the above-mentioned.
상기 건식 조립 과립의 평균 입경이, 45 내지 900㎛인 것을 특징으로 하는 정제.3. The method according to claim 1 or 2,
Tablets, characterized in that the average particle diameter of the dry granulated granules is 45 to 900㎛.
상기 건식 조립 과립이 느슨한 부피밀도(loose bulk density)가, 0.3 내지 0.8g/㎤인 것을 특징으로 하는 정제.3. The method according to claim 1 or 2,
Tablets, characterized in that the dry granulated granules have a loose bulk density of 0.3 to 0.8 g / cm 3.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JPJP-P-2010-287788 | 2010-12-24 | ||
JP2010287788 | 2010-12-24 |
Publications (2)
Publication Number | Publication Date |
---|---|
KR20120073111A true KR20120073111A (en) | 2012-07-04 |
KR101896700B1 KR101896700B1 (en) | 2018-09-07 |
Family
ID=46707660
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020110138800A KR101896700B1 (en) | 2010-12-24 | 2011-12-21 | Tablet |
Country Status (2)
Country | Link |
---|---|
JP (1) | JP5974469B2 (en) |
KR (1) | KR101896700B1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20180110826A (en) * | 2017-03-30 | 2018-10-11 | 한미약품 주식회사 | Pharmaceutical composition comprising ibuprofen and acetaminophen and preparation method thereof |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6140570B2 (en) * | 2013-08-13 | 2017-05-31 | ライオン株式会社 | Ibuprofen-containing tablet and method for producing the same |
JP6141472B2 (en) * | 2016-03-02 | 2017-06-07 | 大原薬品工業株式会社 | Method for producing valsartan-containing tablets |
WO2017195796A1 (en) * | 2016-05-10 | 2017-11-16 | 日本臓器製薬株式会社 | Method for manufacturing acetaminophen preparation |
JP7163015B2 (en) * | 2016-10-31 | 2022-10-31 | エスエス製薬株式会社 | oral solid composition |
US11458102B2 (en) * | 2017-11-09 | 2022-10-04 | Nippon Zoki Pharmaceutical Co., Ltd. | Acetaminophen preparation, and method for producing same |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS56110612A (en) | 1980-02-08 | 1981-09-01 | Yamanouchi Pharmaceut Co Ltd | Readily disintegrable and absorbable compression molded article of slightly soluble drug |
EP0172014B1 (en) * | 1984-08-17 | 1991-01-23 | The Upjohn Company | Formulations of ibuprofen |
WO1997030699A2 (en) * | 1996-02-21 | 1997-08-28 | The Boots Company Plc | Dosage form of ibuprofen |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ZA855250B (en) * | 1984-08-17 | 1986-02-26 | Upjohn Co | Stable,high dose,high bulk density ibuprofen granulations for tablet and capsule manufacturing |
JP4040878B2 (en) * | 1999-12-09 | 2008-01-30 | レキット ベンキーザー ヘルスケア (ユーケイ) リミテッド | Remedy |
JP4643899B2 (en) * | 2003-10-20 | 2011-03-02 | エスエス製薬株式会社 | Ibuprofen-containing tablet and method for producing the same |
JP4717414B2 (en) * | 2004-11-08 | 2011-07-06 | 富田製薬株式会社 | Low melting point drug-containing granule and tablet produced using the same |
JP2007137896A (en) * | 2007-02-23 | 2007-06-07 | Aska Pharmaceutical Co Ltd | Ibuprofen-containing pharmaceutical preparation |
-
2011
- 2011-12-12 JP JP2011270872A patent/JP5974469B2/en active Active
- 2011-12-21 KR KR1020110138800A patent/KR101896700B1/en active IP Right Grant
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS56110612A (en) | 1980-02-08 | 1981-09-01 | Yamanouchi Pharmaceut Co Ltd | Readily disintegrable and absorbable compression molded article of slightly soluble drug |
EP0172014B1 (en) * | 1984-08-17 | 1991-01-23 | The Upjohn Company | Formulations of ibuprofen |
WO1997030699A2 (en) * | 1996-02-21 | 1997-08-28 | The Boots Company Plc | Dosage form of ibuprofen |
Non-Patent Citations (1)
Title |
---|
[특허 문헌] |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20180110826A (en) * | 2017-03-30 | 2018-10-11 | 한미약품 주식회사 | Pharmaceutical composition comprising ibuprofen and acetaminophen and preparation method thereof |
Also Published As
Publication number | Publication date |
---|---|
JP2012144520A (en) | 2012-08-02 |
KR101896700B1 (en) | 2018-09-07 |
JP5974469B2 (en) | 2016-08-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Fini et al. | Fast dispersible/slow releasing ibuprofen tablets | |
JP2015147812A (en) | Method for producing orally disintegrating tablet | |
JP6062168B2 (en) | Formulation containing herbal medicine-derived component and method for producing the same | |
CA2861480C (en) | Oral composition comprising .alpha.,.alpha.,.alpha.-trifluorothymidine (ftd), 5-chloro-6-(2-iminopyrrolidine-1-yl)methyl-2,4(1h,3h)-pyrimidine dione hydrochloride (tpi) | |
KR20120073111A (en) | Tablet | |
JP6433066B2 (en) | Tablet and production method thereof | |
JP2007191419A (en) | Pimobendan preparation for oral administration | |
JP6090610B2 (en) | Tablet manufacturing method | |
JP5208729B2 (en) | Method for producing sustained-release tablets | |
JP5663238B2 (en) | Oral solid preparation and method for producing the same | |
JP2000336027A (en) | Method for suppressing debonding of multilayer tablet | |
KR101677775B1 (en) | Tablet for oral administration having excellent disintegrability and dissolvability | |
JP6407084B2 (en) | Tablet and production method thereof | |
JP7419057B2 (en) | Tablets and coated tablets | |
JP2000063269A (en) | Solid preparation | |
JP2017066133A (en) | Ibuprofen-containing solid preparation with high stability and quick-acting properties | |
JP2012046454A (en) | Tablet for internal use and method for producing the same | |
US10016471B2 (en) | Solid pharmaceutical compositions of brown algae | |
JP7515253B2 (en) | Solid pharmaceutical preparations | |
JPH02286614A (en) | Acetoaminophene preparation | |
JP2020094022A (en) | Excipient granules, tablet and method for producing tablet | |
JP6407085B2 (en) | Tablet and production method thereof | |
JP7425560B2 (en) | Method for manufacturing solid preparations | |
JP6895856B2 (en) | Method for manufacturing solid preparations and tablets | |
JP2023095091A (en) | Tablet comprising dry aluminum hydroxide gel |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A201 | Request for examination | ||
E902 | Notification of reason for refusal | ||
E90F | Notification of reason for final refusal | ||
E701 | Decision to grant or registration of patent right | ||
GRNT | Written decision to grant |