JPWO2010119851A1 - Orally disintegrating tablets - Google Patents
Orally disintegrating tablets Download PDFInfo
- Publication number
- JPWO2010119851A1 JPWO2010119851A1 JP2011509290A JP2011509290A JPWO2010119851A1 JP WO2010119851 A1 JPWO2010119851 A1 JP WO2010119851A1 JP 2011509290 A JP2011509290 A JP 2011509290A JP 2011509290 A JP2011509290 A JP 2011509290A JP WO2010119851 A1 JPWO2010119851 A1 JP WO2010119851A1
- Authority
- JP
- Japan
- Prior art keywords
- mass
- particles
- coating
- orally disintegrating
- drug
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000006191 orally-disintegrating tablet Substances 0.000 title claims abstract description 34
- 239000002245 particle Substances 0.000 claims abstract description 86
- 239000011248 coating agent Substances 0.000 claims abstract description 78
- 229940079593 drug Drugs 0.000 claims abstract description 46
- 239000003814 drug Substances 0.000 claims abstract description 46
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 32
- 235000019640 taste Nutrition 0.000 claims abstract description 29
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims abstract description 22
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims abstract description 22
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims abstract description 22
- 229960000913 crospovidone Drugs 0.000 claims abstract description 21
- 230000008961 swelling Effects 0.000 claims abstract description 17
- 239000007900 aqueous suspension Substances 0.000 claims abstract description 12
- 238000000576 coating method Methods 0.000 claims description 47
- 239000007787 solid Substances 0.000 claims description 24
- 239000007788 liquid Substances 0.000 claims description 3
- 239000000725 suspension Substances 0.000 abstract 1
- 239000003826 tablet Substances 0.000 description 36
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 30
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 26
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 26
- 239000000047 product Substances 0.000 description 21
- 230000000873 masking effect Effects 0.000 description 17
- 239000001856 Ethyl cellulose Substances 0.000 description 16
- 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 16
- 235000019325 ethyl cellulose Nutrition 0.000 description 16
- 229920001249 ethyl cellulose Polymers 0.000 description 16
- 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 15
- 229960001948 caffeine Drugs 0.000 description 15
- 210000000214 mouth Anatomy 0.000 description 15
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 14
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- 239000001087 glyceryl triacetate Substances 0.000 description 13
- 235000013773 glyceryl triacetate Nutrition 0.000 description 13
- 235000010355 mannitol Nutrition 0.000 description 13
- 229960005489 paracetamol Drugs 0.000 description 13
- 238000002360 preparation method Methods 0.000 description 13
- 229960002622 triacetin Drugs 0.000 description 13
- 229930195725 Mannitol Natural products 0.000 description 12
- 239000000594 mannitol Substances 0.000 description 12
- 229960001855 mannitol Drugs 0.000 description 12
- 239000004014 plasticizer Substances 0.000 description 12
- 229920002261 Corn starch Polymers 0.000 description 11
- 239000008120 corn starch Substances 0.000 description 11
- 229940099112 cornstarch Drugs 0.000 description 11
- 239000006185 dispersion Substances 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- 229920002472 Starch Polymers 0.000 description 9
- 235000019658 bitter taste Nutrition 0.000 description 9
- 238000011156 evaluation Methods 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 8
- 239000008213 purified water Substances 0.000 description 8
- 235000019698 starch Nutrition 0.000 description 8
- 239000008107 starch Substances 0.000 description 8
- 239000004386 Erythritol Substances 0.000 description 7
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 239000007910 chewable tablet Substances 0.000 description 7
- 235000019414 erythritol Nutrition 0.000 description 7
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 7
- 229940009714 erythritol Drugs 0.000 description 7
- 235000000346 sugar Nutrition 0.000 description 7
- 229920003169 water-soluble polymer Polymers 0.000 description 7
- 235000003599 food sweetener Nutrition 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 239000003765 sweetening agent Substances 0.000 description 6
- 108010011485 Aspartame Proteins 0.000 description 5
- 239000004376 Sucralose Substances 0.000 description 5
- WMGSQTMJHBYJMQ-UHFFFAOYSA-N aluminum;magnesium;silicate Chemical compound [Mg+2].[Al+3].[O-][Si]([O-])([O-])[O-] WMGSQTMJHBYJMQ-UHFFFAOYSA-N 0.000 description 5
- 239000000605 aspartame Substances 0.000 description 5
- 235000010357 aspartame Nutrition 0.000 description 5
- 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 5
- 229960003438 aspartame Drugs 0.000 description 5
- -1 epilysole Chemical compound 0.000 description 5
- 230000000704 physical effect Effects 0.000 description 5
- 235000019408 sucralose Nutrition 0.000 description 5
- 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 5
- 150000008163 sugars Chemical class 0.000 description 5
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 4
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 4
- 239000007884 disintegrant Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 239000003205 fragrance Substances 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 238000005507 spraying Methods 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 3
- 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 3
- 230000001055 chewing effect Effects 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
- 230000000052 comparative effect Effects 0.000 description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 210000003296 saliva Anatomy 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 2
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 2
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 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
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 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
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 235000019596 Masking bitterness Nutrition 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
- 229920000881 Modified starch Polymers 0.000 description 2
- 244000228451 Stevia rebaudiana Species 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
- 229930006000 Sucrose Natural products 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 2
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 2
- 235000010724 Wisteria floribunda Nutrition 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- 235000010358 acesulfame potassium Nutrition 0.000 description 2
- 229960004998 acesulfame potassium Drugs 0.000 description 2
- 239000000619 acesulfame-K Substances 0.000 description 2
- 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 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 235000013339 cereals Nutrition 0.000 description 2
- 229940068682 chewable tablet Drugs 0.000 description 2
- 239000007931 coated granule Substances 0.000 description 2
- 239000011247 coating layer Substances 0.000 description 2
- 230000006866 deterioration Effects 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-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
- 239000000314 lubricant Substances 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- CPJSUEIXXCENMM-UHFFFAOYSA-N phenacetin Chemical compound CCOC1=CC=C(NC(C)=O)C=C1 CPJSUEIXXCENMM-UHFFFAOYSA-N 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 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 2
- 229940085605 saccharin sodium Drugs 0.000 description 2
- 238000010008 shearing Methods 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 229960002920 sorbitol Drugs 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 150000005846 sugar alcohols Chemical class 0.000 description 2
- 239000000892 thaumatin Substances 0.000 description 2
- 235000010436 thaumatin 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
- 239000001069 triethyl citrate Substances 0.000 description 2
- 235000013769 triethyl citrate Nutrition 0.000 description 2
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 2
- 235000013311 vegetables Nutrition 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- AJZJIYUOOJLBAU-CEAXSRTFSA-N (2r,3r)-2,3-dihydroxybutanedioic acid;n,n,2-trimethyl-3-phenothiazin-10-ylpropan-1-amine Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.C1=CC=C2N(CC(CN(C)C)C)C3=CC=CC=C3SC2=C1.C1=CC=C2N(CC(CN(C)C)C)C3=CC=CC=C3SC2=C1 AJZJIYUOOJLBAU-CEAXSRTFSA-N 0.000 description 1
- YQSHYGCCYVPRDI-UHFFFAOYSA-N (4-propan-2-ylphenyl)methanamine Chemical compound CC(C)C1=CC=C(CN)C=C1 YQSHYGCCYVPRDI-UHFFFAOYSA-N 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
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-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
- LBKUQHSINDZGJA-UHFFFAOYSA-N 1-phenylpropan-1-ol;hydrochloride Chemical compound Cl.CCC(O)C1=CC=CC=C1 LBKUQHSINDZGJA-UHFFFAOYSA-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
- PVXPPJIGRGXGCY-DJHAAKORSA-N 6-O-alpha-D-glucopyranosyl-alpha-D-fructofuranose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@](O)(CO)O1 PVXPPJIGRGXGCY-DJHAAKORSA-N 0.000 description 1
- RLFWWDJHLFCNIJ-UHFFFAOYSA-N Aminoantipyrine Natural products CN1C(C)=C(N)C(=O)N1C1=CC=CC=C1 RLFWWDJHLFCNIJ-UHFFFAOYSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- DBAKFASWICGISY-BTJKTKAUSA-N Chlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 DBAKFASWICGISY-BTJKTKAUSA-N 0.000 description 1
- UDKCHVLMFQVBAA-UHFFFAOYSA-M Choline salicylate Chemical compound C[N+](C)(C)CCO.OC1=CC=CC=C1C([O-])=O UDKCHVLMFQVBAA-UHFFFAOYSA-M 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- BALXUFOVQVENIU-GNAZCLTHSA-N Ephedrine hydrochloride Chemical compound Cl.CN[C@@H](C)[C@H](O)C1=CC=CC=C1 BALXUFOVQVENIU-GNAZCLTHSA-N 0.000 description 1
- 235000001453 Glycyrrhiza echinata Nutrition 0.000 description 1
- 244000303040 Glycyrrhiza glabra Species 0.000 description 1
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 description 1
- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 description 1
- BIVBRWYINDPWKA-VLQRKCJKSA-L Glycyrrhizinate dipotassium Chemical compound [K+].[K+].O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C(O)=O)C([O-])=O)[C@@H]1O[C@H](C([O-])=O)[C@@H](O)[C@H](O)[C@H]1O BIVBRWYINDPWKA-VLQRKCJKSA-L 0.000 description 1
- HSRJKNPTNIJEKV-UHFFFAOYSA-N Guaifenesin Chemical compound COC1=CC=CC=C1OCC(O)CO HSRJKNPTNIJEKV-UHFFFAOYSA-N 0.000 description 1
- 229920003114 HPC-L Polymers 0.000 description 1
- 229920003116 HPC-SSL Polymers 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 235000019501 Lemon oil Nutrition 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 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
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 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
- 239000004698 Polyethylene Substances 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- UKNGDQSYPNBJAO-UHFFFAOYSA-N Tiaramide hydrochloride Chemical compound Cl.C1CN(CCO)CCN1C(=O)CN1C(=O)SC2=CC=C(Cl)C=C21 UKNGDQSYPNBJAO-UHFFFAOYSA-N 0.000 description 1
- NTCYWJCEOILKNG-ROLPUNSJSA-N [(1r,2s)-1-hydroxy-1-phenylpropan-2-yl]-dimethylazanium;chloride Chemical compound Cl.CN(C)[C@@H](C)[C@H](O)C1=CC=CC=C1 NTCYWJCEOILKNG-ROLPUNSJSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- JUGOREOARAHOCO-UHFFFAOYSA-M acetylcholine chloride Chemical compound [Cl-].CC(=O)OCC[N+](C)(C)C JUGOREOARAHOCO-UHFFFAOYSA-M 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-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
- 229960003556 aminophylline Drugs 0.000 description 1
- FQPFAHBPWDRTLU-UHFFFAOYSA-N aminophylline Chemical compound NCCN.O=C1N(C)C(=O)N(C)C2=C1NC=N2.O=C1N(C)C(=O)N(C)C2=C1NC=N2 FQPFAHBPWDRTLU-UHFFFAOYSA-N 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- VEQOALNAAJBPNY-UHFFFAOYSA-N antipyrine Chemical compound CN1C(C)=CC(=O)N1C1=CC=CC=C1 VEQOALNAAJBPNY-UHFFFAOYSA-N 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
- 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
- 230000015572 biosynthetic process Effects 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
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 229950008138 carmellose Drugs 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229940046978 chlorpheniramine maleate Drugs 0.000 description 1
- 229960002688 choline salicylate Drugs 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229960004415 codeine phosphate Drugs 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 229960005168 croscarmellose Drugs 0.000 description 1
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 229960003596 cyproheptadine hydrochloride Drugs 0.000 description 1
- ZPMVNZLARAEGHB-UHFFFAOYSA-N cyproheptadine hydrochloride (anhydrous) Chemical compound Cl.C1CN(C)CCC1=C1C2=CC=CC=C2C=CC2=CC=CC=C21 ZPMVNZLARAEGHB-UHFFFAOYSA-N 0.000 description 1
- 229960003782 dextromethorphan hydrobromide Drugs 0.000 description 1
- PGZIKUPSQINGKT-UHFFFAOYSA-N dialuminum;dioxido(oxo)silane Chemical compound [Al+3].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O.[O-][Si]([O-])=O PGZIKUPSQINGKT-UHFFFAOYSA-N 0.000 description 1
- 229960000920 dihydrocodeine Drugs 0.000 description 1
- RBOXVHNMENFORY-DNJOTXNNSA-N dihydrocodeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC RBOXVHNMENFORY-DNJOTXNNSA-N 0.000 description 1
- 229940101029 dipotassium glycyrrhizinate Drugs 0.000 description 1
- 229940120889 dipyrone Drugs 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229960002534 ephedrine hydrochloride Drugs 0.000 description 1
- 229960003072 epinephrine hydrochloride Drugs 0.000 description 1
- SBNKFTQSBPKMBZ-UHFFFAOYSA-N ethenzamide Chemical compound CCOC1=CC=CC=C1C(N)=O SBNKFTQSBPKMBZ-UHFFFAOYSA-N 0.000 description 1
- 229960004667 ethyl cellulose Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 235000021552 granulated sugar Nutrition 0.000 description 1
- 229960002146 guaifenesin Drugs 0.000 description 1
- 229920001519 homopolymer Polymers 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 239000001341 hydroxy propyl starch Substances 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 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 1
- 235000013828 hydroxypropyl starch Nutrition 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 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 description 1
- 229960000991 ketoprofen Drugs 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
- 229940010454 licorice Drugs 0.000 description 1
- 229940087305 limonene Drugs 0.000 description 1
- 235000001510 limonene Nutrition 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 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
- 230000018984 mastication Effects 0.000 description 1
- 238000010077 mastication Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229960003464 mefenamic acid Drugs 0.000 description 1
- HYYBABOKPJLUIN-UHFFFAOYSA-N mefenamic acid Chemical compound CC1=CC=CC(NC=2C(=CC=CC=2)C(O)=O)=C1C HYYBABOKPJLUIN-UHFFFAOYSA-N 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- DJGAAPFSPWAYTJ-UHFFFAOYSA-M metamizole sodium Chemical compound [Na+].O=C1C(N(CS([O-])(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 DJGAAPFSPWAYTJ-UHFFFAOYSA-M 0.000 description 1
- 229920003145 methacrylic acid copolymer Polymers 0.000 description 1
- 229940117841 methacrylic acid copolymer Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- LZULAZTXJLWELL-UHFFFAOYSA-N methyl hex-5-ynoate Chemical compound COC(=O)CCCC#C LZULAZTXJLWELL-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960002900 methylcellulose Drugs 0.000 description 1
- 229940051020 methylephedrine hydrochloride Drugs 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- 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 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
- 229960005301 pentazocine Drugs 0.000 description 1
- VOKSWYLNZZRQPF-GDIGMMSISA-N pentazocine Chemical compound C1C2=CC=C(O)C=C2[C@@]2(C)[C@@H](C)[C@@H]1N(CC=C(C)C)CC2 VOKSWYLNZZRQPF-GDIGMMSISA-N 0.000 description 1
- 229960003893 phenacetin Drugs 0.000 description 1
- 229960005222 phenazone Drugs 0.000 description 1
- 229960002895 phenylbutazone Drugs 0.000 description 1
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 235000019814 powdered cellulose Nutrition 0.000 description 1
- 229920003124 powdered cellulose Polymers 0.000 description 1
- 229960002789 procaterol hydrochloride Drugs 0.000 description 1
- 229940100486 rice starch Drugs 0.000 description 1
- 229960002052 salbutamol Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 229960004025 sodium salicylate Drugs 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 229940057070 sugarcane extract Drugs 0.000 description 1
- 229940032330 sulfuric acid Drugs 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 description 1
- 229960000401 tranexamic acid Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 229940100445 wheat starch 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- 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
- A61K31/60—Salicylic acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
Landscapes
- Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Medicinal Preparation (AREA)
Abstract
種々の不快な味を有する薬物に適用ができ、食感が良好で、崩壊性がよく、薬物の不快な味がマスキングされた口腔内崩壊錠を提供する。(A)不快な味を有する薬物がコーティング剤で被覆された薬物粒子と、(B)平均粒径50μm以下、膨潤量が5(g)water/(g)product以上、及び5質量%水懸濁液の粘度(25℃)が20mPa・s以下であるクロスポビドン粒子とを含有する口腔内崩壊錠。Disclosed is an orally disintegrating tablet which can be applied to drugs having various unpleasant tastes, has a good texture, has good disintegration, and masks the unpleasant taste of drugs. (A) Drug particles in which a drug having an unpleasant taste is coated with a coating agent, (B) an average particle size of 50 μm or less, a swelling amount of 5 (g) water / (g) product or more, and 5% by mass water suspension An orally disintegrating tablet containing crospovidone particles having a viscosity (25 ° C.) of a suspension of 20 mPa · s or less.
Description
本発明は、不快な味を有する薬物粒子を含有する口腔内崩壊錠に関するものであり、詳細には、食感が良好で、崩壊性がよく、薬物の不快な味がマスキングされた口腔内崩壊錠に関するものである。 The present invention relates to an orally disintegrating tablet containing drug particles having an unpleasant taste, and in particular, an oral disintegration in which the texture is good, the disintegration is good, and the unpleasant taste of the drug is masked It relates to locks.
近年、種々薬物のチュアブル錠または口腔内崩壊錠といった水無しで服用させる錠剤への適用が図られている。しかし、苦味等不快な味を有する薬物に関しては、チュアブル錠または口腔内崩壊錠への配合が比較的閾値の高いもの、すなわち不快な味の弱いものに限定されているのが実情である。従って、様々な強さの不快な味を有する薬物に汎用され、チュアブル錠または口腔内崩壊錠の特性を損なうことがなく、かつバイオアベイラビリティを低下させることのない、実用レベルのマスキング技術が望まれている。 In recent years, application to various tablets such as chewable tablets or orally disintegrating tablets that can be taken without water has been attempted. However, regarding drugs having an unpleasant taste such as a bitter taste, the fact is that the incorporation into chewable tablets or orally disintegrating tablets is limited to those having a relatively high threshold, that is, those having an unpleasant taste. Therefore, there is a demand for a masking technique at a practical level that is widely used for drugs with various unpleasant tastes, does not impair the characteristics of chewable tablets or orally disintegrating tablets, and does not reduce bioavailability. ing.
不快な味を有する薬物は数多く存在するが、薬物の不快な味の強さによってマスキング方法が異なる。具体的にはフレーバー、甘味剤等を添加する等嬌味によってマスキングする方法や、薬物粒子に高分子基剤等を用いたコーティングを施すことによるマスキング方法等が知られている。嬌味によるマスキングの方法においては、その方法のみでの不快な味のマスキングは困難であり、ごく限られた薬物にしか適用できない。従って不快な味の閾値が低い薬物をマスキングするには、高分子基剤等によるコーティングによって、口腔内における薬物の放出を抑制する必要がある。 There are many drugs having an unpleasant taste, but the masking method differs depending on the intensity of the unpleasant taste of the drug. Specifically, a masking method by adding a flavor, a sweetening agent, or the like, and a masking method by coating a drug particle with a polymer base or the like is known. In the method of masking by taste, masking of unpleasant taste by that method alone is difficult, and it can be applied only to limited drugs. Therefore, in order to mask a drug having a low unpleasant taste threshold, it is necessary to suppress the release of the drug in the oral cavity by coating with a polymer base or the like.
不快な味の閾値が低い薬物にコーティングを施しチュアブル錠または口腔内崩壊錠とする場合、通常のコーティング量では、製造時における打錠圧によるコーティング膜の微細な割れや、服用時における口腔内での咀嚼や摩擦による剥れ等の影響で、十分に不快な味の抑制ができない場合がある。これを解決するためには、通常よりも厚いコーティング層とする方法が考えられるが、その結果、消化管内における薬物の十分な放出を確保できず、通常製剤と比較するとバイオアベイラビリティが低下してしまうという問題がある。 When a drug with a low unpleasant taste threshold is coated to make a chewable tablet or orally disintegrating tablet, the normal coating amount may cause fine cracks in the coating film due to tableting pressure during production, In some cases, it is not possible to sufficiently suppress unpleasant taste due to the effect of chewing or peeling due to friction. In order to solve this, a method of making the coating layer thicker than usual can be considered, but as a result, sufficient release of the drug in the gastrointestinal tract cannot be ensured, and bioavailability is reduced as compared with a normal preparation. There is a problem.
本発明は上記事情に鑑みなされたもので、種々の不快な味を有する薬物に適用ができ、食感が良好で、崩壊性がよく、薬物の不快な味がマスキングされた口腔内崩壊錠を提供することを目的とする。
なお、本発明において、チュアブル錠は、錠剤を口腔内に含み、咀嚼により、あるいは唾液との接触や舌と上顎間のシェア(摩擦)によって、錠剤を口腔内で崩壊・溶解させ服用する錠剤である。口腔内崩壊錠は、錠剤を口腔内に含み、主に唾液との接触や舌と上顎間のシアーによって崩壊・溶解させる錠剤である(咀嚼を否定するものではない)。このように、通常、チュアブル錠と口腔内崩壊錠は、何れも咀嚼や唾液との接触、上顎と舌間のシェアで錠剤を口腔内で崩壊させる錠剤であり、水で服用する錠剤よりも薬物の不快な味を感じやすい点で本発明の共通する課題を有するものであって、明確には区別されない。
以下、本発明において、チュアブル錠及び口腔内崩壊錠を、特に断りがない限り、統合して「口腔内崩壊錠」と記す。The present invention has been made in view of the above circumstances, and is an orally disintegrating tablet that can be applied to drugs having various unpleasant tastes, has a good texture, good disintegration, and masks the unpleasant taste of drugs. The purpose is to provide.
In the present invention, the chewable tablet is a tablet containing the tablet in the oral cavity, which is taken by being disintegrated / dissolved in the oral cavity by chewing or by contact with saliva or shearing (friction) between the tongue and upper jaw. is there. An orally disintegrating tablet is a tablet that contains a tablet in the oral cavity and is disintegrated and dissolved mainly by contact with saliva and by shearing between the tongue and upper jaw (mastication is not denied). As described above, chewable tablets and orally disintegrating tablets are usually tablets that disintegrate in the oral cavity by chewing, contact with saliva, and sharing between the upper jaw and tongue, and are more effective than tablets taken with water. The present invention has a common problem in that it is easy to feel an unpleasant taste, and is not clearly distinguished.
Hereinafter, in the present invention, chewable tablets and orally disintegrating tablets are collectively referred to as “orally disintegrating tablets” unless otherwise specified.
本発明者らは、上記目的を達成するため鋭意検討した結果、崩壊剤として知られるクロスポビドンの中で、特定の物性を有するクロスポビドン、つまり、平均粒径50μm以下、膨潤量が5(g)water/(g)product以上、及び5質量%水懸濁液の粘度が20mPa・s以下であるクロスポビドン粒子が、錠剤の崩壊性(速度)を向上させるだけでなく、口腔内での咀嚼や摩擦による薬物粒子の被覆の壊れや剥れを抑制して薬物の不快な味マスキングに優れ、さらに口腔内で錠剤が崩壊する際、錠剤を構成する各粒子によるざらつき感を低減して食感を著しく向上させる作用を有することを知見し、本発明をなすに至ったものである。 As a result of intensive studies to achieve the above object, the present inventors have found that crospovidone having specific physical properties among crospovidones known as disintegrants, that is, an average particle size of 50 μm or less and a swelling amount of 5 (g ) Crospovidone particles having a water / (g) product of 5% by weight and a 5% by weight aqueous suspension with a viscosity of 20 mPa · s or less not only improve the disintegration (speed) of the tablet but also chew in the oral cavity. Prevents drug particles from being broken or peeled off due to friction and masking, resulting in an unpleasant taste masking of the drug. Further, when the tablet disintegrates in the mouth, the texture of each particle that makes up the tablet is reduced to reduce the texture. It has been found that it has the effect of significantly improving the above, and has led to the present invention.
従って、本発明は下記口腔内崩壊錠を提供する。
[1].(A)不快な味を有する薬物がコーティング剤で被覆された薬物粒子と、(B)平均粒径50μm以下、膨潤量が5(g)water/(g)product以上、及び5質量%水懸濁液の粘度(25℃)が20mPa・s以下であるクロスポビドン粒子とを含有する口腔内崩壊錠。
[2].(B)粒子の含有量が1〜20質量%である[1]記載の口腔内崩壊錠。
[3].(A)粒子中の、薬物に対するコーティング剤のコーティング率が、固形分として1〜60質量%である[1]又は[2]記載の口腔内崩壊錠。Accordingly, the present invention provides the following orally disintegrating tablets.
[1]. (A) Drug particles in which a drug having an unpleasant taste is coated with a coating agent, (B) an average particle size of 50 μm or less, a swelling amount of 5 (g) water / (g) product or more, and 5 mass% water suspension An orally disintegrating tablet comprising crospovidone particles having a viscosity (25 ° C.) of a turbid liquid of 20 mPa · s or less.
[2]. (B) The orally disintegrating tablet according to [1], wherein the content of the particles is 1 to 20% by mass.
[3]. (A) The orally disintegrating tablet according to [1] or [2], wherein the coating rate of the coating agent to the drug in the particles is 1 to 60% by mass as a solid content.
本発明によれば、種々の不快な味を有する薬物に適用ができ、食感が良好で、崩壊性がよく、薬物の不快な味がマスキングされた口腔内崩壊錠を提供することができる。 According to the present invention, it is possible to provide an orally disintegrating tablet which can be applied to drugs having various unpleasant tastes, has a good texture, has good disintegration, and masks the unpleasant taste of drugs.
以下、本発明について詳細に説明する。
本発明の口腔内崩壊錠は、(A)不快な味を有する薬物がコーティング剤で被覆された薬物粒子と、(B)平均粒径50μm以下、膨潤量が5(g)water/(g)product以上、及び5質量%水懸濁液の粘度(25℃)が20mPa・s以下であるクロスポビドン粒子とを含有するものである。Hereinafter, the present invention will be described in detail.
The orally disintegrating tablet of the present invention comprises (A) drug particles in which a drug having an unpleasant taste is coated with a coating agent, (B) an average particle size of 50 μm or less, and a swelling amount of 5 (g) water / (g) The product contains crospovidone particles having a product of 5 mass% or more and a viscosity (25 ° C.) of a 5 mass% water suspension of 20 mPa · s or less.
(A)薬物粒子
薬物粒子(薬物粒子(A))は、不快な味を有する薬物がコーティング剤で被覆されたものである。
不快な味を有する薬物としては、アセトアミノフェン、アスピリン、イブプロフェン、エテンザミド、フェナセチン、メフェナム酸、アンチピリン、フェニルブタゾン、スルピリン、ジクロフェナトリウム、ケトプロフェン、ナプロキセン、エピリゾール、塩酸チアラミド、インドメタシン、ペンタゾシン、塩化アセチルコリン、酒石酸アリメマジン、塩酸シプロヘプタジン、塩酸ジフェドラミン、マレイン酸クロルフェニラミン、リン酸コデイン、リン酸ジヒドロコデイン、臭化水素酸デキストロメトルファン、クエン酸ペントキシベリン、テオフィリン、アミノフィリン、塩酸エフェドリン、塩酸エピネフリン、硫酸サルブタモール、塩酸トリメトキノール、塩酸プロカテロール、塩酸メチルエフェドリン、塩酸フェニルプロパノールアミン、グアイフェネシン、トラネキサム酸、無水カフェイン、カフェイン、サリチル酸コリン、サリチル酸ナトリウム等が挙げられ、1種単独で又は2種以上を併用してもよい。中でも、アセトアミノフェン及びカフェインが好ましい。(A) Drug particles Drug particles (drug particles (A)) are obtained by coating a drug having an unpleasant taste with a coating agent.
Drugs with an unpleasant taste include acetaminophen, aspirin, ibuprofen, etenzamide, phenacetin, mefenamic acid, antipyrine, phenylbutazone, sulpyrine, sodium diclofenate, ketoprofen, naproxen, epilysole, thiaramide hydrochloride, indomethacin, pentazocine, chloride Acetylcholine, alimemazine tartrate, cyproheptadine hydrochloride, diphedramine hydrochloride, chlorpheniramine maleate, codeine phosphate, dihydrocodeine phosphate, dextromethorphan hydrobromide, pentoxyberine citrate, theophylline, aminophylline, ephedrine hydrochloride, epinephrine hydrochloride, sulfuric acid Salbutamol, Trimethquinol hydrochloride, Procaterol hydrochloride, Methylephedrine hydrochloride, Phenylpropanol hydrochloride Emissions, guaifenesin, tranexamic acid, caffeine anhydrous, caffeine, choline salicylate, sodium salicylate, and the like, may be used in combination alone or in admixture. Of these, acetaminophen and caffeine are preferable.
本発明におけるコーティング剤とは、薬物の表面に存在している成分をいい、水難溶性高分子化合物及び可塑剤からなるコーティング基剤を含むものである。この基剤を用いることにより、苦味マスキング性及び溶出性が向上する。なお、「水難溶性高分子化合物」とは、水10000mLに溶解する量が1g又は1mL未満である化合物をいう。水難溶性高分子化合物としては、具体的には、エチルセルロース、アミノアクリルメタクリレートコポリマー、メタクリル酸コポリマー等が挙げられる。これらは1種単独で又は2種以上を適宜組み合わせて用いることができる。中でも、使用性、臭いの点から、エチルセルロースが好ましい。水難溶性高分子化合物の含有量は、コーティングしやすさ、可塑性、溶出性等を考慮すると、コーティング剤の総固形分に対して40〜90質量%が好ましく、40〜80質量%がより好ましく、50〜70質量%が特に好ましい。 The coating agent in the present invention refers to a component present on the surface of a drug, and includes a coating base composed of a poorly water-soluble polymer compound and a plasticizer. By using this base, bitterness masking property and dissolution property are improved. The “poorly water-soluble polymer compound” refers to a compound whose amount dissolved in 10,000 mL of water is 1 g or less than 1 mL. Specific examples of the poorly water-soluble polymer compound include ethyl cellulose, aminoacryl methacrylate copolymer, and methacrylic acid copolymer. These can be used individually by 1 type or in combination of 2 or more types. Of these, ethyl cellulose is preferred from the viewpoint of usability and odor. The content of the poorly water-soluble polymer compound is preferably 40 to 90% by mass, more preferably 40 to 80% by mass, based on the total solid content of the coating agent, in consideration of ease of coating, plasticity, elution and the like. 50-70 mass% is especially preferable.
本発明におけるコーティング剤には可塑剤が含まれることが好ましい。可塑剤はコーティング剤を含む溶液に適度な展延性を与え、成膜しやすくする機能を有すると推測される。可塑剤としては、トリアセチン、クエン酸トリエチル等の医薬品添加物規格((株)薬事日報社)等の公定書に記載されているものが挙げられる。これらは、1種単独で又は2種以上を適宜組み合わせて用いることができる。成膜性を考慮するとトリアセチン、クエン酸トリエチルが好ましく、トリアセチンがさらに好ましい。可塑剤の含有量はコーティング剤の総固形分に対して5〜50質量%が好ましく、10〜40質量%がより好ましい。また、可塑剤:水難溶性高分子化合物の総固形分(質量比)=0.05:1〜0.5:1が好ましく、0.1:1〜0.4:1がより好ましい。 The coating agent in the present invention preferably contains a plasticizer. The plasticizer is presumed to have a function of imparting appropriate spreadability to the solution containing the coating agent and facilitating film formation. Examples of the plasticizer include those described in official documents such as standards for pharmaceutical additives such as triacetin and triethyl citrate (Pharmaceutical Daily Inc.). These can be used individually by 1 type or in combination of 2 or more types. Considering film formability, triacetin and triethyl citrate are preferable, and triacetin is more preferable. 5-50 mass% is preferable with respect to the total solid of a coating agent, and, as for content of a plasticizer, 10-40 mass% is more preferable. The total solid content (mass ratio) of the plasticizer: poorly water-soluble polymer compound is preferably 0.05: 1 to 0.5: 1, more preferably 0.1: 1 to 0.4: 1.
コーティング剤には、マスキング効果向上の点から、さらに溶出制御剤を配合してもよい。溶出制御剤としては、乳糖、トレハロース、白糖等の糖、マンニトール、エリスリトール、キシリトール、ソルビトール等の糖アルコール等が挙げられ、これらは1種単独で又は2種以上を適宜組み合わせて用いることができる。溶出制御剤は含まれなくてもよく、その含有量はコーティング剤の総固形分に対して0〜60質量%が好ましく、0〜50質量%がより好ましい。 In order to improve the masking effect, the coating agent may further contain an elution control agent. Examples of the elution control agent include sugars such as lactose, trehalose and sucrose, and sugar alcohols such as mannitol, erythritol, xylitol and sorbitol, and these can be used alone or in combination of two or more. The elution control agent may not be contained, and the content thereof is preferably 0 to 60% by mass, and more preferably 0 to 50% by mass with respect to the total solid content of the coating agent.
コーティング剤には甘味剤を配合してもよい。甘味剤としては、アスパルテーム、スクラロース、エリスリトール、アセスルファムカリウム、サッカリンナトリウム、ステビア抽出物、ソーマチン、サトウキビ抽出物、パラチノース加熱物、カンゾウ等が挙げられ、1種単独で又は2種以上を適宜組み合わせて用いることができる。中でも、アスパルテーム、スクラロースが好ましい。甘味剤の含有量はコーティング剤の総固形分に対して0〜50質量%が好ましい。 A sweetener may be blended in the coating agent. Examples of sweeteners include aspartame, sucralose, erythritol, acesulfame potassium, saccharin sodium, stevia extract, thaumatin, sugarcane extract, heated palatinose, licorice, etc. Can do. Of these, aspartame and sucralose are preferable. The content of the sweetener is preferably 0 to 50% by mass with respect to the total solid content of the coating agent.
コーティング率は、薬物(被被覆物)に対して、固形分として1〜60質量%の範囲で設定するとよい。なお、コーティング率とは、薬物(被被覆物)100質量%とした場合のコーティング剤の質量%をいう。コーティング率は、1質量%以上で十分なマスキング効果が得られ、60質量%を超えると効果が飽和している上、薬物放出性が悪くなるおそれがある。安定なマスキング効果を得る点から、コーティング率の下限は3質量%以上がより好ましく、5質量%以上、特に8質量%以上がさらに好ましい。また、薬物放出性の点から、コーティング率は低く設定することが好ましく、具体的には、例えば、上限は50質量%以下が好ましく、40質量%以下、30質量%以下、25質量%以下、15質量%以下、10質量%以下とすることが好ましい。本発明では、特定のクロスポビドンを用いることにより、製造(特に打錠)時や服用時の衝撃や摩擦などの外力によるコーティングの劣化(割れ、剥れなど)が抑制されるので、低いコーティング率でも良好な味マスキング効果を得ることができる。 A coating rate is good to set in the range of 1-60 mass% as solid content with respect to a drug (coating material). In addition, a coating rate means the mass% of a coating agent when a drug (coating object) is 100 mass%. When the coating rate is 1% by mass or more, a sufficient masking effect is obtained, and when it exceeds 60% by mass, the effect is saturated and the drug release property may be deteriorated. From the viewpoint of obtaining a stable masking effect, the lower limit of the coating rate is more preferably 3% by mass or more, further preferably 5% by mass or more, and particularly preferably 8% by mass or more. Further, from the viewpoint of drug release, it is preferable to set the coating rate low. Specifically, for example, the upper limit is preferably 50% by mass or less, 40% by mass or less, 30% by mass or less, 25% by mass or less, It is preferable to set it as 15 mass% or less and 10 mass% or less. In the present invention, by using a specific crospovidone, coating deterioration (cracking, peeling, etc.) due to external force such as impact or friction during manufacture (especially tableting) or taking is suppressed, so a low coating rate However, a good taste masking effect can be obtained.
(A)粒子の平均粒径は75〜500μmが好ましく、150〜300μmがより好ましい。なお、本発明において、平均粒径は、1000μm、850μm、500μm、355μm、250μm、150μm、75μmの内径75mmのふるいを用い、サンプル量10gで、日局「粉体粒度測定法」第2法に基づき試験を行い測定した際の累積の50%粒子径とする。 (A) 75-500 micrometers is preferable and the average particle diameter of particle | grains has more preferable 150-300 micrometers. In the present invention, the average particle size is 1000 μm, 850 μm, 500 μm, 355 μm, 250 μm, 150 μm, and 75 μm sieves with an inner diameter of 75 mm. Based on the test and measurement, the cumulative particle size is 50%.
薬物粒子(A)の含有量は、服用性及び錠剤物性(硬度、摩損度、崩壊性等)の点から、口腔内崩壊錠に対して80質量%以下が好ましく、70質量%以下がより好ましく、65質量%以下が特に好ましい。下限は特に限定されず、前記上限以下の範囲で各薬物の有効性を考慮した設定含有量とすることができる。 The content of the drug particles (A) is preferably 80% by mass or less, more preferably 70% by mass or less with respect to the orally disintegrating tablet from the viewpoint of ingestion and tablet physical properties (hardness, friability, disintegration, etc.). 65 mass% or less is particularly preferable. The lower limit is not particularly limited, and can be a set content considering the effectiveness of each drug within the range below the upper limit.
(B)クロスポビドン粒子
本発明のクロスポビドン粒子(クロスポビドン粒子(B))は、(1)平均粒径50μm以下、(2)膨潤量が5(g)water/(g)product以上、及び(3)5質量%水懸濁液の粘度が20mPa・s以下である。クロスポビドンとは、架橋ポリビニルピロリドンであり、1−エテニル−2−ピロリジノンホモポリマーという化学名を有し架橋されている重合物である。(B) Crospovidone particles The crospovidone particles (crospovidone particles (B)) of the present invention have (1) an average particle size of 50 μm or less, (2) a swelling amount of 5 (g) water / (g) product or more, and (3) The viscosity of the 5% by mass aqueous suspension is 20 mPa · s or less. Crospovidone is a crosslinked polyvinylpyrrolidone, which is a polymer having a chemical name of 1-ethenyl-2-pyrrolidinone homopolymer and crosslinked.
口腔内崩壊錠は口腔内で(特に舌と上あごの間で)シェアをかけて崩壊させたり噛みくだいたりするため、その際のシェアや衝撃で薬物のコーティングが剥れ不快な味が出てしまうが、上記物性のクロスポビドン粒子(B)を配合した錠剤は、口腔内でシェアをかけた際にクリーミーに崩れ、摩擦や衝撃によるコーティング層への影響が抑制され、コーティングが劣化せずに崩壊でき、結果、食感が良好で、崩壊性がよく、薬物の不快な味のマスキング効果を高めることができる。 Orally disintegrating tablets disintegrate or chew in the mouth (especially between the tongue and upper jaw), causing the drug coating to peel off and unpleasant taste due to the share and impact However, tablets containing crospovidone particles (B) with the above physical properties collapse into creamy when applied in the oral cavity, and the influence on the coating layer due to friction and impact is suppressed, and the coating does not deteriorate. It can disintegrate and, as a result, has a good texture, good disintegration, and can enhance the masking effect of the unpleasant taste of the drug.
以下に、本発明で使用されるクロスポビドン粒子(B)の特性について説明する。
(1)平均粒径50μm以下
本発明で使用されるクロスポビドン粒子(B)の平均粒径は50μm以下であり、10〜50μmが好ましく、30μm以下がより好ましい。平均粒径が50μmを超えると、錠剤崩壊時におけるコーティング粒子間での摩擦を和らげザラツキを抑えるクッション的役割を果たせず、またクロスポビドン粒子自体のザラつきも感じ、食感が悪くなる。また、10μm未満だと、流動性の悪化により混合均一性が悪くなるおそれがある。尚、平均粒子径はレーザー散乱回折法粒度分布測定装置(ベックマン・コールター(株)製、LS 13 320)により測定する。Below, the characteristic of the crospovidone particle | grains (B) used by this invention is demonstrated.
(1) Average particle diameter of 50 μm or less The average particle diameter of the crospovidone particles (B) used in the present invention is 50 μm or less, preferably 10 to 50 μm, more preferably 30 μm or less. If the average particle size exceeds 50 μm, the friction between the coating particles at the time of tablet disintegration is reduced and the cushioning role for suppressing the roughness is not achieved, and the roughness of the crospovidone particles themselves is also felt, resulting in poor texture. On the other hand, when the thickness is less than 10 μm, the uniformity of mixing may be deteriorated due to the deterioration of fluidity. The average particle size is measured by a laser scattering diffraction particle size distribution analyzer (LS 13 320, manufactured by Beckman Coulter, Inc.).
(2)膨潤量が5(g)water/(g)product以上
本発明で使用されるクロスポビドン粒子(B)の膨潤量は5(g)water/(g)product以上であり、5〜20(g)water/(g)productが好ましく、5.5〜8.5(g)water/(g)productがより好ましい。膨潤量が5(g)water/(g)product未満の場合、水分の吸収が少なく、錠剤中で崩壊剤としての機能が十分でなく崩壊性が悪化する。また、20(g)water/(g)productを超えると、崩壊剤が水分を吸収しすぎ、口中の水分がなくなることにより食感が悪化するおそれがある。なお、本発明の膨潤量は、以下のようにして求めることができる。
(i)1g(M0)のサンプルと20℃の蒸留水50mLを遠心管に加え、振とうさせ15分間静止後、遠心分離(相対遠心加速度850[×g];15分)にかけ、上澄みを取り除き、膨潤したサンプルの質量(M1g)を測定し、概算の膨潤量M1(M1/M0)を算出する。
(ii)次に、蒸留水量を2M1mLに変えて(1)の操作を行い、膨潤したサンプルの質量(M2g)を測定し、正確な膨潤量M2(M2/M0)を算出する。この正確な膨潤量M2(M2/M0)が本発明の膨潤量である。(2) The swelling amount is 5 (g) water / (g) product or more The swelling amount of the crospovidone particles (B) used in the present invention is 5 (g) water / (g) product or more, and 5 to 20 (G) water / (g) product is preferable, and 5.5 to 8.5 (g) water / (g) product is more preferable. When the swelling amount is less than 5 (g) water / (g) product, the absorption of moisture is small, the function as a disintegrant is not sufficient in the tablet, and the disintegration property is deteriorated. Moreover, when it exceeds 20 (g) water / (g) product, there exists a possibility that a disintegrating agent may absorb a water | moisture content too much and food texture may deteriorate because the water | moisture content in a mouth is lose | eliminated. The swelling amount of the present invention can be determined as follows.
(I) Add 1 g (M0) sample and 50 mL of distilled water at 20 ° C. to a centrifuge tube, shake and let stand for 15 minutes, then centrifuge (relative centrifugal acceleration 850 [× g]; 15 minutes) and remove the supernatant. The mass (M1g) of the swollen sample is measured, and an approximate swelling amount M1 (M1 / M0) is calculated.
(Ii) Next, the amount of distilled water is changed to 2M1 mL, the operation of (1) is performed, the mass (M2g) of the swollen sample is measured, and an accurate swelling amount M2 (M2 / M0) is calculated. This exact swelling amount M2 (M2 / M0) is the swelling amount of the present invention.
(3)5質量%水懸濁液の粘度(25℃)が20mPa・s以下
本発明で使用されるクロスポビドン粒子(B)の5質量%水懸濁液の粘度(25℃)は20mPa・s以下である。下限は特に限定されないが、10mPa・s程度である。水懸濁液の粘度が20mPa・sを超えると、錠剤崩壊時に水分を吸収することによりゲル状に変化し、錠剤内部への水の浸入を防いでしまい、崩壊性が悪化する。粘度は、B型粘度計(東機産業(株)、RB−80L)を用いて、以下の条件(ローターNo.H−1、測定回転数30rpm、測定時間1分)で測定する。(3) The viscosity (25 ° C.) of the 5% by mass aqueous suspension is 20 mPa · s or less The viscosity (25 ° C.) of the 5% by mass aqueous suspension of the crospovidone particles (B) used in the present invention is 20 mPa · s. s or less. Although a minimum is not specifically limited, It is about 10 mPa * s. When the viscosity of the aqueous suspension exceeds 20 mPa · s, it absorbs moisture at the time of tablet disintegration and changes into a gel, which prevents water from entering the tablet and deteriorates disintegration. The viscosity is measured using a B-type viscometer (Toki Sangyo Co., Ltd., RB-80L) under the following conditions (rotor No. H-1, measurement rotation speed 30 rpm, measurement time 1 minute).
上述の(1)平均粒径50μm以下、(2)膨潤量が5(g)water/(g)product以上、及び(3)5質量%水懸濁液の粘度(25℃)が20mPa・s以下の条件を全て満たすクロスポビドンとしては、例えば、BASFジャパン(株)製コリドンCL−SF(平均粒子径15〜35μm、膨潤量7.5〜9.0(g)water/(g)product、5質量%水懸濁液の粘度(25℃)が15〜20mPa・s)や、BASFジャパン(株)製コリドンCL−F(平均粒子径25〜45μm、膨潤量5.0〜6.5(g)water/(g)product、5質量%水懸濁液の粘度(25℃)が110〜16mPa・s)等が挙げられる。 (1) Average particle size of 50 μm or less, (2) Swelling amount is 5 (g) water / (g) product or more, and (3) Viscosity (25 ° C.) of 5 mass% water suspension is 20 mPa · s. As crospovidone satisfying all the following conditions, for example, BASF Japan Co., Ltd. Kollidon CL-SF (average particle size 15-35 μm, swelling amount 7.5-9.0 (g) water / (g) product, Viscosity (25 ° C.) of a 5% by mass aqueous suspension is 15 to 20 mPa · s), BASF Japan Co., Ltd. Kollidon CL-F (average particle size 25 to 45 μm, swelling amount 5.0 to 6.5 ( g) water / (g) product, viscosity (25 ° C.) of 5 mass% aqueous suspension is 110 to 16 mPa · s), and the like.
本発明のクロスポビドン粒子(B)の含有量は、口腔内崩壊錠に対して1〜20質量%が好ましく、下限は2質量%以上がより好ましく、5質量%が特に好ましい。上限は15質量%以下がより好ましく、10質量%が特に好ましい。クロスポビドン粒子(B)を、20質量%を超えて配合すると、硬度及び摩損度が悪化するおそれがあり、1質量%未満であると崩壊性が悪化するおそれがある。 The content of the crospovidone particles (B) of the present invention is preferably 1 to 20% by mass relative to the orally disintegrating tablet, the lower limit is more preferably 2% by mass or more, and particularly preferably 5% by mass. The upper limit is more preferably 15% by mass or less, and particularly preferably 10% by mass. If the crospovidone particles (B) are added in an amount exceeding 20% by mass, the hardness and friability may be deteriorated, and if it is less than 1% by mass, the disintegration property may be deteriorated.
本発明の口腔内崩壊錠には、本発明の効果を損なわない範囲で、任意成分を配合することができる。任意成分としては、他の有効成分、賦形剤、本発明のクロスポリドン粒子(B)以外の崩壊剤、甘味剤、酸味剤、香料、滑沢剤、色素等を配合することができる。これらは1種単独で又は2種以上を適宜組み合わせ、適量を配合することができる。 In the orally disintegrating tablet of the present invention, an optional component can be blended within a range not impairing the effects of the present invention. As optional components, other active ingredients, excipients, disintegrants other than the crosspolydon particles (B) of the present invention, sweeteners, sour agents, fragrances, lubricants, pigments and the like can be blended. These may be used alone or in appropriate combination of two or more, and an appropriate amount may be blended.
他の有効成分としては、例えば、メタケイ酸アルミン酸マグネシウム、ケイ酸アルミン酸マグネシウム等の制酸剤が好適に配合し得る。これらは市販のものを用いることができ、ノイシリンUS2、ノイシリンUFL2(富士化学工業(株)製)等を用いることができる(含有量:口腔内崩壊錠に対して5〜20質量%)。 As other active ingredients, for example, antacids such as magnesium aluminate metasilicate and magnesium aluminate silicate can be suitably blended. These can use a commercially available thing, Neusilin US2, Neusilin UFL2 (made by Fuji Chemical Industry Co., Ltd.) etc. can be used (content: 5-20 mass% with respect to an orally disintegrating tablet).
賦形剤としては、セルロース類の粉体、糖類の粉体、デンプン類、二酸化ケイ素等の粉体等が挙げられる(含有量:口腔内崩壊錠に対して通常5〜60質量%)。セルロース類の粉体として具体的には、結晶セルロース、粉末セルロース、カルメロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、低置換度ヒドロキシプロピルセルロース、ヒドロキシメチルセルロース、メチルセルロース、エチルセルロース等が挙げられる。 Examples of the excipient include cellulose powder, saccharide powder, starch, silicon dioxide powder and the like (content: usually 5 to 60% by mass with respect to the orally disintegrating tablet). Specific examples of the cellulose powder include crystalline cellulose, powdered cellulose, carmellose, hydroxypropylcellulose, hydroxypropylmethylcellulose, low-substituted hydroxypropylcellulose, hydroxymethylcellulose, methylcellulose, and ethylcellulose.
糖類の粉体として具体的には、単糖類、二糖類以上の多糖類(砂糖(グラニュー糖等)、乳糖、麦芽糖、キシロース、異性化乳糖等)、糖アルコール(パラチニット、ソルビトール、ラクチトール、エリスリトール、キシリトール、還元澱粉糖化物、マルチトール、マンニトール等)、水飴、異性化糖類、オリゴ糖、スクロース、トレハロース、還元澱粉糖化物(還元澱粉分解物)等が好ましい。 Specific examples of the saccharide powder include monosaccharides, disaccharides and higher polysaccharides (sugar (granulated sugar, etc.), lactose, maltose, xylose, isomerized lactose, etc.), sugar alcohols (palatinite, sorbitol, lactitol, erythritol, Xylitol, reduced starch saccharified product, maltitol, mannitol, etc.), starch syrup, isomerized sugar, oligosaccharide, sucrose, trehalose, reduced starch saccharified product (reduced starch decomposed product) and the like are preferable.
デンプン類の粉体として具体的には、トウモロコシデンプン(コーンスターチ)、バレイショデンプン(ポテトスターチ)、コムギデンプン、コメデンプン等のデンプン、ヒドロキシプロピルスターチ、部分α化デンプン等のデンプン誘導体等が好ましく、トウモロコシデンプン(コーンスターチ)がより好ましい。 Specifically, the starch powder is preferably corn starch (corn starch), potato starch (potato starch), starch such as wheat starch or rice starch, starch derivative such as hydroxypropyl starch or partially pregelatinized starch, etc. Starch (corn starch) is more preferred.
崩壊剤としては、例えば、クロスカルメロース等を用いることができる。甘味剤としては、例えば、サッカリンナトリウム、アスパルテーム、ステビア、グリチルリチン酸ジカリウム、アセスルファムカリウム、ソーマチン、スクラロース等を用いることができる(含有量:口腔内崩壊錠に対して通常0.05〜10質量%)。酸味剤としては、例えば、クエン酸、酒石酸、リンゴ酸、コハク酸、フマル酸、乳酸又はそれらの塩等を用いることができる(含有量:口腔内崩壊錠に対して通常0.2〜3質量%)。香料としては、例えば、メントール、リモネン、植物精油(ハッカ油、ミント油、ライチ油、オレンジ油、レモン油等)等を用いることができる。 For example, croscarmellose can be used as the disintegrant. As a sweetening agent, saccharin sodium, aspartame, stevia, dipotassium glycyrrhizinate, acesulfame potassium, thaumatin, sucralose, etc. can be used (content: 0.05-10 mass% normally with respect to an orally disintegrating tablet), for example. As the sour agent, for example, citric acid, tartaric acid, malic acid, succinic acid, fumaric acid, lactic acid or a salt thereof can be used (content: usually 0.2 to 3 mass with respect to the orally disintegrating tablet). %). As a fragrance | flavor, menthol, limonene, vegetable essential oils (mint oil, mint oil, lychee oil, orange oil, lemon oil etc.) etc. can be used, for example.
滑沢剤としては、ステアリン酸マグネシウム、ステアリン酸カルシウム等を挙げることができる(含有量:口腔内崩壊錠に対して通常0.5質量%以下、好ましくは0.05〜0.2質量%)。 Examples of the lubricant include magnesium stearate and calcium stearate (content: usually 0.5% by mass or less, preferably 0.05 to 0.2% by mass with respect to the orally disintegrating tablet).
本発明の口腔内崩壊錠の製造方法について下記に示す。
(A)粒子は、例えば、一次平均粒径150〜300μmの薬物粒子に、水難溶性高分子化合物及び可塑剤を含むコーティング剤をコーティングすることにより、得ることができる。具体的には、水難溶性高分子化合物及び可塑剤を含むコーティング剤分散液又は溶液を、薬物粒子に噴霧することにより得ることができる。分散媒又は溶媒としては、水、エタノール等が挙げられる。It shows below about the manufacturing method of the orally disintegrating tablet of this invention.
(A) The particles can be obtained, for example, by coating drug particles having a primary average particle size of 150 to 300 μm with a coating agent containing a poorly water-soluble polymer compound and a plasticizer. Specifically, it can be obtained by spraying a coating agent dispersion or solution containing a poorly water-soluble polymer compound and a plasticizer onto drug particles. Examples of the dispersion medium or solvent include water and ethanol.
コーティングは流動層を有するコーティング装置により行われ、特に、ワースター法による装置が好ましい。ワースター法とは、流動層底部から上部に向かって原料粒子と噴霧液が同方向に流動する方法であり、タンジェンシャルボトムスプレー、ボトムスプレー等がある。ワースター法によるコーティング装置においては、粒子の凝集を抑制しやすいことから粗粉の抑制に適している。 The coating is performed by a coating apparatus having a fluidized bed, and a Waster method apparatus is particularly preferable. The Wurster method is a method in which the raw material particles and the spray liquid flow in the same direction from the bottom of the fluidized bed toward the top, and includes tangential bottom spray and bottom spray. The coating apparatus using the Wurster method is suitable for suppressing coarse powder because it is easy to suppress aggregation of particles.
コーティングを行う際の条件としては、特に限定されず、通常用いられている条件が使用できる。例えば、コーティング装置の排気温度は、20〜70℃が好ましく、給気温度は60〜90℃が好ましい。 Conditions for coating are not particularly limited, and commonly used conditions can be used. For example, the exhaust temperature of the coating apparatus is preferably 20 to 70 ° C, and the supply air temperature is preferably 60 to 90 ° C.
本発明の口腔内崩壊錠は、上記(A)粒子、(B)粒子及び任意成分を混合し、打錠することにより、得ることができる。打錠圧等の成型条件は、打錠機、成分の種類や含有量、錠剤の径等により異なるが、錠剤物性等を考慮して、適宜調整する。 The orally disintegrating tablet of the present invention can be obtained by mixing the above (A) particles, (B) particles and optional components, and tableting. Molding conditions such as tableting pressure vary depending on the tableting machine, the type and content of ingredients, the diameter of the tablet, etc., but are adjusted as appropriate in consideration of tablet physical properties and the like.
本発明の口腔内崩壊錠の大きさは特に限定されないが、直径6〜25mm程度が好ましく、その錠剤硬度は、3〜20kgfが好ましく、5〜15kgfがより好ましい。なお、錠剤硬度は、錠剤を金床の上に垂直に立て、移動プランジャーで錠剤に静的圧力を加え、錠剤が破壊されるまでに要する力を表し、錠剤硬度測定器(富山産業(株))を用いて測定することができる。また、口腔内崩壊速度は60秒未満が好ましく、30秒未満がより好ましい。なお、口腔内崩壊速度とは、錠剤を口腔内に入れ、舌と上顎でシアーをかけて錠剤が崩壊し終わるまでの時間をいう。 The size of the orally disintegrating tablet of the present invention is not particularly limited, but is preferably about 6 to 25 mm in diameter, and the tablet hardness is preferably 3 to 20 kgf, more preferably 5 to 15 kgf. The tablet hardness represents the force required for the tablet to break by standing upright on the anvil and applying static pressure to the tablet with a moving plunger. )). The oral disintegration rate is preferably less than 60 seconds, and more preferably less than 30 seconds. The oral disintegration rate refers to the time from when the tablet is put into the oral cavity until the tablet is disintegrated by applying shear with the tongue and upper jaw.
以下、実施例及び比較例を示し、本発明を具体的に説明するが、本発明は下記の実施例に制限されるものではない。なお、下記の例において特に明記のない場合は、組成の「%」は質量%を示す。 EXAMPLES Hereinafter, although an Example and a comparative example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example. In the following examples, unless otherwise specified, “%” in the composition represents mass%.
[調製例1:アセトアミノフェンコーティング粒子1(コーティング率8.8%)]
日局精製水にエチルセルロース30質量%水分散液(商品名セリオスコート:旭化成ケミカルズ)、糖類及び可塑剤を入れ、よく攪拌して、下表に記載する組成のコーティング剤溶液を得た。
<コーティング剤溶液組成>
エチルセルロース30質量%水分散液 178.3g
マンニトール 26.7g
トリアセチン 13.4g
日局精製水 249.6g
合計 468.0g
固形分濃度 (20%)
固形分に対するエチルセルロース濃度:57.1%
固形分に対するマンニトール濃度:28.6%
固形分に対するトリアセチン濃度:14.3%[Preparation Example 1: Acetaminophen coated particles 1 (coating rate 8.8%)]
A 30% by weight aqueous dispersion of ethyl cellulose (trade name: Serios Coat: Asahi Kasei Chemicals), sugars and a plasticizer were added to JP purified water, and stirred well to obtain a coating agent solution having the composition described in the table below.
<Coating agent solution composition>
Ethylcellulose 30 mass% aqueous dispersion 178.3 g
Mannitol 26.7g
Triacetin 13.4g
JP purified water 249.6g
Total 468.0g
Solid content (20%)
Ethylcellulose concentration based on solid content: 57.1%
Mannitol concentration based on solid content: 28.6%
Triacetin concentration based on solid content: 14.3%
次いで、流動層造粒機マルチプレックスMP−01ワースター仕様(パウレック社製)を用い、アセトアミノフェン粒子800gを入れ、これに給気温度65℃、排気温度28〜32℃になる風量で、上記で調製したコーティング剤溶液を、10g/minの速度で、アセトアミノフェン粒子に対するコーティング率8.8%になるように噴霧してコーティングを行った。これを給気80℃で30分間キュアリングし、アセトアミノフェンコーティング粒子1(平均粒径300μm)を得た。コーティング率8.8%であった。 Next, using a fluidized bed granulator multiplex MP-01 Wurster specification (manufactured by POWREC), 800 g of acetaminophen particles are added, and the air flow is 65 ° C. and the exhaust temperature is 28 to 32 ° C. The coating agent solution prepared in (1) was sprayed at a rate of 10 g / min so that the coating rate with respect to acetaminophen particles was 8.8%. This was cured at an air supply of 80 ° C. for 30 minutes to obtain acetaminophen coated particles 1 (average particle size 300 μm). The coating rate was 8.8%.
[調製例2:カフェインコーティング粒子1(コーティング率30.0%)]
日局精製水にエチルセルロース30質量%水分散液(商品名セリオスコート:旭化成ケミカルズ)、糖類及び可塑剤を入れ、よく攪拌して、下表に記載する組成のコーティング剤溶液を得た。
<コーティング剤溶液組成>
エチルセルロース30質量%水分散液 742.9g
マンニトール 111.4g
トリアセチン 55.7g
日局精製水 1040.0g
合計 1950.0g
固形分濃度 (20%)
固形分に対するエチルセルロース濃度:57.1%
固形分に対するマンニトール濃度:28.6%
固形分に対するトリアセチン濃度:14.3%[Preparation Example 2: Caffeine coated particles 1 (coating rate 30.0%)]
A 30% by weight aqueous dispersion of ethyl cellulose (trade name: Serios Coat: Asahi Kasei Chemicals), sugars and a plasticizer were added to JP purified water, and stirred well to obtain a coating agent solution having the composition described in the table below.
<Coating agent solution composition>
Ethylcellulose 30 mass% aqueous dispersion 742.9 g
Mannitol 111.4g
Triacetin 55.7g
JP purified water 1040.0g
Total 1950.0g
Solid content (20%)
Ethylcellulose concentration based on solid content: 57.1%
Mannitol concentration based on solid content: 28.6%
Triacetin concentration based on solid content: 14.3%
次いで、流動層造粒機マルチプレックスMP−01ワースター仕様(パウレック社製)を用い、カフェイン粒子1000gを入れ、これに給気温度80℃、排気温度35〜45℃になる風量で、上記で調製したコーティング剤溶液を、20g/minの速度で、カフェイン粒子に対するコーティング率30.0%になるように噴霧してコーティングを行った。これを給気80℃で30分間キュアリングし、カフェインコーティング粒子1(平均粒径370μm)を得た。コーティング率30.0%であった。 Next, using a fluidized bed granulator multiplex MP-01 Wurster specification (manufactured by POWREC), 1000 g of caffeine particles are added, and the air volume is 80 ° C. and the exhaust temperature is 35 to 45 ° C. Coating was performed by spraying the prepared coating agent solution at a rate of 20 g / min so that the coating rate with respect to caffeine particles was 30.0%. This was cured at an air supply of 80 ° C. for 30 minutes to obtain caffeine coating particles 1 (average particle size of 370 μm). The coating rate was 30.0%.
[調製例3:エリスリトール造粒品の調製]
エリスリトール(エリスリトール、三栄源エフ・エフ・アイ(株)製)3200gとトウモロコシデンプン(精製乾燥滅菌コーンスターチ、松谷化学工業(株)製)600gを混ぜ、スパイラーフローSFC−5型(フロイント産業(株)製)に入れ、給気温度90℃、排気温度35〜45℃で、ヒドロキシプロピルセルロース6質量%水溶液(HPC−L、日本曹達(株)製)を2400g噴霧し造粒した。[Preparation Example 3: Preparation of erythritol granulated product]
Erythritol (erythritol, Saneigen FFI Co., Ltd.) 3200g and corn starch (refined and sterilized cornstarch, Matsutani Chemical Industry Co., Ltd.) 600g are mixed, and Spirer Flow SFC-5 type (Freund Sangyo Co., Ltd.) 2400g of hydroxypropylcellulose 6 mass% aqueous solution (HPC-L, Nippon Soda Co., Ltd.) was sprayed and granulated at an air supply temperature of 90 ° C and an exhaust temperature of 35 to 45 ° C.
[調製例4:マンニトール造粒品の調製]
D−マンニトール(ロケットジャパン(株)製)900gを流動層造粒機マルチプレックスMP−01((株)パウレック製)に入れ、給気温度80℃、排気温度40〜50℃で、ヒドロキシプロピルセルロース12質量%水溶液(HPC−SSL、日本曹達(株)製)を600g噴霧し造粒した。[Preparation Example 4: Preparation of granulated mannitol]
900 g of D-mannitol (manufactured by Rocket Japan Co., Ltd.) was placed in a fluidized bed granulator multiplex MP-01 (manufactured by Paulek Co., Ltd.), and the supply temperature was 80 ° C., the exhaust temperature was 40-50 ° C., and hydroxypropylcellulose 600 g of 12% by mass aqueous solution (HPC-SSL, manufactured by Nippon Soda Co., Ltd.) was sprayed and granulated.
[調製例5:l−メントール/トウモロコシデンプン共粉砕品の調製]
l−メントール1000g及びトウモロコシデンプン(精製乾燥滅菌コーンスターチ、松谷化学工業(株)製)1000gをポリエチレン製の袋(0.6m×0.4m)に投入し、手で良く振り混ぜた。その混合物をφ1.0mmのスクリーンを装着した粉砕機((株)徳寿工作所製、フィオーレF−0型)に投入し20Hzの回転数で粉砕した。その後、粉砕物を目開き850μmの篩で篩過し、目開き850μmの篩を通過しなかった粒子を再度、同条件で粉砕し、目開き850μmの篩を通過した粒子と合わせてl−メントール/トウモロコシデンプン共粉砕品とした。[Preparation Example 5: Preparation of l-menthol / corn starch co-ground product]
1000 g of l-menthol and 1000 g of corn starch (refined and sterilized corn starch, manufactured by Matsutani Chemical Industry Co., Ltd.) were put into a polyethylene bag (0.6 m × 0.4 m) and shaken well by hand. The mixture was put into a pulverizer (Fiore F-0 type, manufactured by Tokuju Kogakusho Co., Ltd.) equipped with a φ1.0 mm screen and pulverized at a rotation speed of 20 Hz. Thereafter, the pulverized product was sieved with a sieve having an opening of 850 μm, and the particles that did not pass through the sieve with an opening of 850 μm were pulverized again under the same conditions and combined with the particles that passed through the sieve with an opening of 850 μm. / Corn starch co-ground product.
[実施例1〜22、比較例1〜7]
調製例1及び2で得られたアセトアミノフェンコーティング粒子1及びカフェインコーティング粒子1を使用し、表2〜4に示す量で各粉末を量り、混合後、ロータリー打錠機(菊水製作所製)で打錠し、直径14.7mmの錠剤を得た。打錠にあたっては錠剤硬度が約8kgf(8〜9kgf)となるように打錠圧を調整した。得られた錠剤について、下記評価を行った。結果を表中に併記する。[Examples 1 to 22, Comparative Examples 1 to 7]
Using the acetaminophen coated particles 1 and caffeine coated particles 1 obtained in Preparation Examples 1 and 2, each powder was weighed in the amounts shown in Tables 2 to 4, and mixed, and then a rotary tableting machine (manufactured by Kikusui Seisakusho). To obtain tablets with a diameter of 14.7 mm. In tableting, the tableting pressure was adjusted so that the tablet hardness was about 8 kgf (8-9 kgf). The following evaluation was performed about the obtained tablet. The results are also shown in the table.
<苦味のマスキング性>
(A)パネラー7人が錠剤1錠を口に含み、舌と上顎でシアーをかけて溶解した際に感じた苦味の強さを下記5段階で評価し平均値を算出した。評価点が3以下であれば許容できる。
(B)パネラー7人が錠剤1錠を口に含み奥歯で3回咀嚼した後、舌と上顎でシアーをかけて溶解した際に感じた苦味の強さを下記5段階で評価し平均値を算出した。評価点が3以下であれば許容できる。
[評価点]
1:苦味を感じない
2:苦味をやや感じる
3:苦味を少し感じる
4:苦味をかなり感じる
5:苦味を非常に感じる<Masking of bitterness>
(A) Seven panelists included one tablet in their mouths, and evaluated the bitterness intensity felt when they were dissolved by applying shear with the tongue and upper jaw, and the average value was calculated. If the evaluation score is 3 or less, it is acceptable.
(B) After 7 panelists put one tablet in their mouth and chewed with their back teeth three times, the bitterness intensity felt when they were melted by applying sheer on the tongue and upper jaw was evaluated in the following five levels, and the average value was calculated. Calculated. If the evaluation score is 3 or less, it is acceptable.
[Evaluation points]
1: Feel no bitterness 2: Feel bitterness slightly 3: Feel bitterness slightly 4: Feel bitterness considerably 5: Feel bitterness very much
<崩壊性>
パネラー7人が錠剤1錠を口に含み、舌と上顎でシアーをかけて錠剤が崩壊し終わるまでの時間を測定した。結果を下記評価基準で示す。崩壊時間が60秒以上だと、コーティング顆粒のコーティングが溶け、苦味マスキング性が劣る。
[評価基準]
○:崩壊時間が平均30秒未満
△:崩壊時間が平均30秒以上60秒未満
×:崩壊時間が平均60秒以上<Disintegration>
Seven panelists included one tablet in their mouth, sheered the tongue and upper jaw, and measured the time until the tablet had disintegrated. A result is shown by the following evaluation criteria. When the disintegration time is 60 seconds or more, the coating of the coated granule dissolves and the bitterness masking property is inferior.
[Evaluation criteria]
○: Collapse time average less than 30 seconds Δ: Collapse time average 30 seconds or more and less than 60 seconds ×: Collapse time average 60 seconds or more
<食感>
パネラー7人が錠剤1錠を口に含み、舌と上顎でシアーをかけて溶解した際に感じたザラツキの強さを下記5段階で評価し平均値を算出した。評価点が2以下であれば許容できる。ザラツキを強く感じるほど、舌と上顎で強くシアーをかけるので、コーティング顆粒同士の摩擦によりコーティングがはがれマスキング性が低下し、錠剤としての服用性が悪化する。
[評価点]
1:ザラツキを感じない
2:ザラツキをやや感じる
3:ザラツキを少し感じる
4:ザラツキをかなり感じる<Food texture>
Seven panelists included one tablet in their mouths, and evaluated the strength of the roughness when they were dissolved by applying shear with the tongue and upper jaw, and the average value was calculated. An evaluation score of 2 or less is acceptable. The stronger the feeling of roughness, the more sheer is applied to the tongue and upper jaw, so that the coating peels off due to the friction between the coated granules and the masking property is lowered, and the dosage as a tablet deteriorates.
[Evaluation points]
1: Does not feel rough 2: Feels slightly rough 3: Feels rough slightly 4: Feels rough
実施例及び比較例で使用した市販崩壊剤について、下記に示す。
[調製例6:アセトアミノフェンコーティング粒子2(コーティング率3.0%)]
日局精製水にエチルセルロース30質量%水分散液(商品名セリオスコート:旭化成ケミカルズ)、糖類及び可塑剤を入れ、よく攪拌して、下表に記載する組成のコーティング剤溶液を得た。
<コーティング剤溶液組成>
エチルセルロース30質量%水分散液 178.3g
マンニトール 26.7g
トリアセチン 13.4g
日局精製水 249.6g
合計 468.0g
固形分濃度 (20%)
固形分に対するエチルセルロース濃度:57.1%
固形分に対するマンニトール濃度:28.6%
固形分に対するトリアセチン濃度:14.3%[Preparation Example 6: Acetaminophen coated particles 2 (coating rate: 3.0%)]
A 30% by weight aqueous dispersion of ethyl cellulose (trade name: Serios Coat: Asahi Kasei Chemicals), sugars and a plasticizer were added to JP purified water, and stirred well to obtain a coating agent solution having the composition described in the table below.
<Coating agent solution composition>
Ethylcellulose 30 mass% aqueous dispersion 178.3 g
Mannitol 26.7g
Triacetin 13.4g
JP purified water 249.6g
Total 468.0g
Solid content (20%)
Ethylcellulose concentration based on solid content: 57.1%
Mannitol concentration based on solid content: 28.6%
Triacetin concentration based on solid content: 14.3%
次いで、流動層造粒機マルチプレックスMP−01ワースター仕様(パウレック社製)を用い、アセトアミノフェン粒子800gを入れ、これに給気温度65℃、排気温度28〜32℃になる風量で、上記で調製したコーティング剤溶液を、10g/minの速度で、アセトアミノフェン粒子に対するコーティング率3.0%になるように噴霧してコーティングを行った。これを給気80℃で30分間キュアリングし、アセトアミノフェンコーティング粒子2(平均粒径290μm)を得た。コーティング率3.0%であった。 Next, using a fluidized bed granulator multiplex MP-01 Wurster specification (manufactured by POWREC), 800 g of acetaminophen particles are added, and the air flow is 65 ° C. and the exhaust temperature is 28 to 32 ° C. Coating was performed by spraying the coating agent solution prepared in step 1 at a rate of 10 g / min so that the coating rate with respect to acetaminophen particles was 3.0%. This was cured at an air supply of 80 ° C. for 30 minutes to obtain acetaminophen coated particles 2 (average particle size of 290 μm). The coating rate was 3.0%.
[調製例7:カフェインコーティング粒子2(コーティング率50.0%)]
日局精製水にエチルセルロース30質量%水分散液(商品名セリオスコート:旭化成ケミカルズ)、糖類及び可塑剤を入れ、よく攪拌して、下表に記載する組成のコーティング剤溶液を得た。
<コーティング剤溶液組成>
エチルセルロース30質量%水分散液 1142.0g
マンニトール 171.6g
トリアセチン 85.8g
日局精製水 1600.6g
合計 3000.0g
固形分濃度 (20%)
固形分に対するエチルセルロース濃度:57.1%
固形分に対するマンニトール濃度:28.6%
固形分に対するトリアセチン濃度:14.3%[Preparation Example 7: Caffeine coating particle 2 (coating rate 50.0%)]
A 30% by weight aqueous dispersion of ethyl cellulose (trade name: Serios Coat: Asahi Kasei Chemicals), sugars and a plasticizer were added to JP purified water, and stirred well to obtain a coating agent solution having the composition described in the table below.
<Coating agent solution composition>
Ethylcellulose 30% by weight aqueous dispersion 1142.0 g
Mannitol 171.6g
Triacetin 85.8g
JP0.6 Purified Water 1600.6g
Total 3000.0g
Solid content (20%)
Ethylcellulose concentration based on solid content: 57.1%
Mannitol concentration based on solid content: 28.6%
Triacetin concentration based on solid content: 14.3%
次いで、流動層造粒機マルチプレックスMP−01ワースター仕様(パウレック社製)を用い、カフェイン粒子1000gを入れ、これに給気温度80℃、排気温度35〜45℃になる風量で、上記で調製したコーティング剤溶液を、20g/minの速度で、カフェイン粒子に対するコーティング率50.0%になるように噴霧してコーティングを行った。これを給気80℃で30分間キュアリングし、カフェインコーティング粒子2(平均粒径370μm)を得た。コーティング率50.0%であった。 Next, using a fluidized bed granulator multiplex MP-01 Wurster specification (manufactured by POWREC), 1000 g of caffeine particles are added, and the air volume is 80 ° C. and the exhaust temperature is 35 to 45 ° C. Coating was performed by spraying the prepared coating agent solution at a rate of 20 g / min so that the coating rate with respect to caffeine particles was 50.0%. This was cured at a supply air of 80 ° C. for 30 minutes to obtain caffeine coating particles 2 (average particle size of 370 μm). The coating rate was 50.0%.
[実施例23〜31]
調製例1、6及び7で得られたアセトアミノフェンコーティング粒子1、2及びカフェインコーティング粒子2を使用し、表5に示す量で各粉末を量り、混合後、ロータリー打錠機(菊水製作所製)で打錠し、直径14.7mm錠剤を得た。打錠にあたっては錠剤硬度が約8kgf(8〜9kgf)となるように打錠圧を調整した。得られた錠剤について、下記評価を行った。結果を表中に併記する。[Examples 23 to 31]
Using the acetaminophen coated particles 1 and 2 and caffeine coated particles 2 obtained in Preparation Examples 1, 6 and 7, each powder was weighed in the amounts shown in Table 5 and mixed, and then a rotary tableting machine (Kikusui Seisakusho) was used. Manufactured) to obtain a tablet having a diameter of 14.7 mm. In tableting, the tableting pressure was adjusted so that the tablet hardness was about 8 kgf (8-9 kgf). The following evaluation was performed about the obtained tablet. The results are also shown in the table.
<使用原料>
アセトアミノフェン(タイコヘルスケアジャパン(株)、SPECIAL GRANULAR)
カフェイン((株)静岡カフェイン工業所、無水カフェイン)
エチルセルロース水分散液(旭化成(株)、セリオスコートEC−30A)
トリアセチン(大八化学工業(株)、トリアセチン)
マンニトール(ロケットジャパン(株)、PEARLITOL 50C)
エリスリトール(三栄源エフ・エフ・アイ(株))
トウモロコシデンプン(松谷化学工業(株)、精製乾燥滅菌コーンスターチ)
l−メントール(東洋薄荷工業(株))
メタケイ酸アルミン酸マグネシウム(富士化学工業(株)ノイシリンUS2)
アスパルテーム(味の素(株)、KKアスパルテーム)
スクラロース(三栄源エフ・エフ・アイ(株)、食品添加物スクラロース)
ステアリン酸マグネシウム(太平化学産業(株)、ステアリン酸マグネシウム 植物性)
香料(高砂香料工業(株)ペパーミントミクロンZD−7741)<Raw materials>
Acetaminophen (Tyco Healthcare Japan Co., Ltd., SPECIAL GRANULAR)
Caffeine (Shizuoka Caffeine Industrial Co., Ltd., anhydrous caffeine)
Ethylcellulose aqueous dispersion (Asahi Kasei Corporation, Cerios Coat EC-30A)
Triacetin (Daihachi Chemical Industry Co., Ltd., Triacetin)
Mannitol (Rocket Japan, PEARLITOL 50C)
Erythritol (Saneigen FFI Co., Ltd.)
Corn starch (Matsutani Chemical Co., Ltd., refined and dried sterilized corn starch)
l-Menthol (Toyo Hikaru Industry Co., Ltd.)
Magnesium aluminate metasilicate (Fuji Chemical Co., Ltd. Neusilin US2)
Aspartame (Ajinomoto Co., Inc., KK Aspartame)
Sucralose (Sanyogen FFI Co., Ltd., food additive sucralose)
Magnesium stearate (Taihei Chemical Industry Co., Ltd., magnesium stearate vegetable)
Fragrance (Takasago Fragrance Industry Co., Ltd. Peppermint Micron ZD-7741)
クロスポビドンに関してコリドンCL−SF及びコリドンCL−Fを他の複数ロットを用いて実施例1〜28の実験を繰り返し行ったところ、同様の結果が得られた。その際のコリドンCL−SF及びコリドンCL−Fの物性は表6の通りであった。 When the experiment of Examples 1-28 was repeated using other lots of Kollidon CL-SF and Kollidon CL-F for crospovidone, similar results were obtained. Table 6 shows the physical properties of Kollidon CL-SF and Kollidon CL-F.
Claims (3)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2009097893 | 2009-04-14 | ||
JP2009097893 | 2009-04-14 | ||
PCT/JP2010/056555 WO2010119851A1 (en) | 2009-04-14 | 2010-04-13 | Orally disintegrating tablet |
Publications (1)
Publication Number | Publication Date |
---|---|
JPWO2010119851A1 true JPWO2010119851A1 (en) | 2012-10-22 |
Family
ID=42982513
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2011509290A Pending JPWO2010119851A1 (en) | 2009-04-14 | 2010-04-13 | Orally disintegrating tablets |
Country Status (2)
Country | Link |
---|---|
JP (1) | JPWO2010119851A1 (en) |
WO (1) | WO2010119851A1 (en) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP5828280B2 (en) * | 2011-12-28 | 2015-12-02 | ライオン株式会社 | Tablet and production method thereof |
WO2018021265A1 (en) * | 2016-07-27 | 2018-02-01 | 沢井製薬株式会社 | Additive composition for orally disintegrating tablet |
WO2018047789A1 (en) | 2016-09-06 | 2018-03-15 | 沢井製薬株式会社 | Orally disintegrating tablet additive composition |
JP2019182818A (en) * | 2018-04-17 | 2019-10-24 | ライオン株式会社 | Intraoral disintegrable tablet for removing tongue coating and method for removing tongue coating |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2005343800A (en) * | 2004-05-31 | 2005-12-15 | Lion Corp | Coated caffeine particle, solid preparation and sleepiness-preventing medicine |
JP2007524575A (en) * | 2003-01-30 | 2007-08-30 | エティファーム | Taste masking coated particles, preparation method thereof, and orally disintegrating tablets containing the coated particles |
WO2007136129A1 (en) * | 2006-05-23 | 2007-11-29 | Takeda Pharmaceutical Company Limited | Oral preparation comprising pioglitazone |
JP2008260712A (en) * | 2007-04-12 | 2008-10-30 | Nipro Corp | Main medicine particle and method for producing the same and intraoral disintegrable tablet |
WO2008149894A1 (en) * | 2007-06-06 | 2008-12-11 | Asahi Kasei Chemicals Corporation | Cellulose fine core particle, and method for production thereof |
WO2008148742A2 (en) * | 2007-06-06 | 2008-12-11 | Basf Se | Pharmaceutical formulation for the production of rapidly disintegrating tablets |
WO2008148734A1 (en) * | 2007-06-06 | 2008-12-11 | Basf Se | Pharmaceutical formulation for the production of chewable tablets and lozenges |
JP2009514845A (en) * | 2005-11-02 | 2009-04-09 | マクニール−ピーピーシー・インコーポレイテッド | Multi-layer coating technology for taste masking |
JP2009179604A (en) * | 2008-01-31 | 2009-08-13 | Kyorin Pharmaceut Co Ltd | Quickly disintegrating tablet in oral cavity |
-
2010
- 2010-04-13 JP JP2011509290A patent/JPWO2010119851A1/en active Pending
- 2010-04-13 WO PCT/JP2010/056555 patent/WO2010119851A1/en active Application Filing
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007524575A (en) * | 2003-01-30 | 2007-08-30 | エティファーム | Taste masking coated particles, preparation method thereof, and orally disintegrating tablets containing the coated particles |
JP2005343800A (en) * | 2004-05-31 | 2005-12-15 | Lion Corp | Coated caffeine particle, solid preparation and sleepiness-preventing medicine |
JP2009514845A (en) * | 2005-11-02 | 2009-04-09 | マクニール−ピーピーシー・インコーポレイテッド | Multi-layer coating technology for taste masking |
WO2007136129A1 (en) * | 2006-05-23 | 2007-11-29 | Takeda Pharmaceutical Company Limited | Oral preparation comprising pioglitazone |
JP2008260712A (en) * | 2007-04-12 | 2008-10-30 | Nipro Corp | Main medicine particle and method for producing the same and intraoral disintegrable tablet |
WO2008149894A1 (en) * | 2007-06-06 | 2008-12-11 | Asahi Kasei Chemicals Corporation | Cellulose fine core particle, and method for production thereof |
WO2008148742A2 (en) * | 2007-06-06 | 2008-12-11 | Basf Se | Pharmaceutical formulation for the production of rapidly disintegrating tablets |
WO2008148734A1 (en) * | 2007-06-06 | 2008-12-11 | Basf Se | Pharmaceutical formulation for the production of chewable tablets and lozenges |
JP2009179604A (en) * | 2008-01-31 | 2009-08-13 | Kyorin Pharmaceut Co Ltd | Quickly disintegrating tablet in oral cavity |
Non-Patent Citations (2)
Title |
---|
JPN6014009474; Volker Buhler, Kollidon Polyvinylpyrrolidone excipients for thepharmaceutical industry, Kollidon, 9t * |
JPN6014051247; 医薬品製剤化方略と新技術 , 2007, 319-322, 株式会社シーエムシー出版 * |
Also Published As
Publication number | Publication date |
---|---|
WO2010119851A1 (en) | 2010-10-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5352474B2 (en) | Orally disintegrating tablet and method for producing the same | |
JP5752227B2 (en) | Orally disintegrating tablets | |
JP5680898B2 (en) | Fast disintegrating tablets with reduced bitterness | |
WO2007074856A1 (en) | Method of producing solid preparation disintegrating in the oral cavity | |
JP5259880B2 (en) | Oral | |
JP5215172B2 (en) | Dry type quick-disintegrating tablet | |
JP6919119B2 (en) | A compressed solid pharmaceutical composition containing a γ-aminobutyric acid derivative substituted at the 3-position. | |
JP2010053047A (en) | Irbesartan-containing pharmaceutical composition with good elution property and orally disintegrable tablet | |
JP5870690B2 (en) | Orally disintegrating tablet and method for producing the same | |
WO2007086457A1 (en) | Quickly disintegrating tablet produced by direct dry-tabletting | |
JP4444626B2 (en) | Orally disintegrating tablets | |
JPWO2010119851A1 (en) | Orally disintegrating tablets | |
EP2591781B1 (en) | Particle coating preparation | |
WO2007086846A1 (en) | Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them | |
JP5664225B2 (en) | Unpleasant taste masking particles and oral preparations containing the same | |
JP5978335B2 (en) | Irbesartan-containing pharmaceutical composition with good dissolution and orally disintegrating tablet | |
JP5828280B2 (en) | Tablet and production method thereof | |
KR102060738B1 (en) | Bitter taste masked pharmaceutical formulation comprising esomeprazole free base or alkali salt thereof and preparation method thereof | |
JP2004026675A (en) | Particle for chewable type medicinal preparation, chewable type medicinal preparation using the same, and method for suppressing unpleasant taste of the same | |
JP4716063B2 (en) | Unpleasant taste masking particles and oral preparations containing the same | |
JP5275815B2 (en) | Orally disintegrating tablets and bitterness-suppressing preparations containing risperidone | |
TWI468189B (en) | Oral internal disintegrating tablet and its manufacturing method | |
JP5530716B2 (en) | Crude drug-containing tablet and method for producing herbal medicine-bearing particles for herbal medicine-containing tablet | |
JP5575119B2 (en) | Orally disintegrating tablets | |
JP2005139086A (en) | Quick-disintegration preparation |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130121 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140304 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20140430 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20140509 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140530 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20141209 |