JP6812104B2 - Oral solid composition - Google Patents
Oral solid composition Download PDFInfo
- Publication number
- JP6812104B2 JP6812104B2 JP2015255829A JP2015255829A JP6812104B2 JP 6812104 B2 JP6812104 B2 JP 6812104B2 JP 2015255829 A JP2015255829 A JP 2015255829A JP 2015255829 A JP2015255829 A JP 2015255829A JP 6812104 B2 JP6812104 B2 JP 6812104B2
- Authority
- JP
- Japan
- Prior art keywords
- unpleasant taste
- polymer compound
- alkali metal
- metal salt
- acidic 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.)
- Active
Links
- 239000008247 solid mixture Substances 0.000 title claims description 22
- 229940079593 drug Drugs 0.000 claims description 64
- 239000003814 drug Substances 0.000 claims description 64
- 229920000642 polymer Polymers 0.000 claims description 49
- 150000001875 compounds Chemical class 0.000 claims description 48
- -1 alkali metal salt Chemical class 0.000 claims description 45
- 235000019640 taste Nutrition 0.000 claims description 45
- 230000002378 acidificating effect Effects 0.000 claims description 43
- 229910052783 alkali metal Inorganic materials 0.000 claims description 41
- 125000005395 methacrylic acid group Chemical group 0.000 claims description 26
- 229920001577 copolymer Polymers 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 18
- 230000000873 masking effect Effects 0.000 claims description 17
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 16
- 229960002373 loxoprofen Drugs 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 229910052751 metal Inorganic materials 0.000 claims description 4
- 239000002184 metal Substances 0.000 claims description 4
- WORCCYVLMMTGFR-UHFFFAOYSA-M loxoprofen sodium Chemical group [Na+].C1=CC(C(C([O-])=O)C)=CC=C1CC1C(=O)CCC1 WORCCYVLMMTGFR-UHFFFAOYSA-M 0.000 claims 4
- 150000003839 salts Chemical class 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 35
- 239000008187 granular material Substances 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 229920002678 cellulose Polymers 0.000 description 10
- 239000001913 cellulose Substances 0.000 description 10
- 238000005469 granulation Methods 0.000 description 10
- 230000003179 granulation Effects 0.000 description 10
- YMBXTVYHTMGZDW-UHFFFAOYSA-N loxoprofen Chemical compound C1=CC(C(C(O)=O)C)=CC=C1CC1C(=O)CCC1 YMBXTVYHTMGZDW-UHFFFAOYSA-N 0.000 description 10
- 239000002245 particle Substances 0.000 description 10
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 10
- 235000012239 silicon dioxide Nutrition 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 9
- 235000019658 bitter taste Nutrition 0.000 description 9
- 238000009472 formulation Methods 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- 238000002156 mixing Methods 0.000 description 7
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 6
- 239000001768 carboxy methyl cellulose Substances 0.000 description 6
- 239000006185 dispersion Substances 0.000 description 6
- 238000009775 high-speed stirring Methods 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 239000008213 purified water Substances 0.000 description 6
- 229920002261 Corn starch Polymers 0.000 description 5
- 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 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000011248 coating agent Substances 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 239000008120 corn starch Substances 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 238000004513 sizing Methods 0.000 description 5
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 5
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 5
- 239000000454 talc Substances 0.000 description 5
- 229910052623 talc Inorganic materials 0.000 description 5
- 235000012222 talc Nutrition 0.000 description 5
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 4
- 108010011485 Aspartame Proteins 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 239000004372 Polyvinyl alcohol Substances 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 4
- 235000010358 acesulfame potassium Nutrition 0.000 description 4
- 229960004998 acesulfame potassium Drugs 0.000 description 4
- 239000000619 acesulfame-K Substances 0.000 description 4
- 239000000605 aspartame Substances 0.000 description 4
- 235000010357 aspartame Nutrition 0.000 description 4
- 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 4
- 229960003438 aspartame Drugs 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 239000003205 fragrance Substances 0.000 description 4
- 230000007794 irritation Effects 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 229920002451 polyvinyl alcohol Polymers 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 239000001069 triethyl citrate Substances 0.000 description 4
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 4
- 235000013769 triethyl citrate Nutrition 0.000 description 4
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 3
- 229920000881 Modified starch Polymers 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 229920003144 amino alkyl methacrylate copolymer Polymers 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000007884 disintegrant Substances 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 230000037406 food intake Effects 0.000 description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 3
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 231100000017 mucous membrane irritation Toxicity 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- SJIXRGNQPBQWMK-UHFFFAOYSA-N 2-(diethylamino)ethyl 2-methylprop-2-enoate Chemical compound CCN(CC)CCOC(=O)C(C)=C SJIXRGNQPBQWMK-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 229920003134 Eudragit® polymer Polymers 0.000 description 2
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 235000019606 astringent taste Nutrition 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 238000000748 compression moulding Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000007771 core particle Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- GDCRSXZBSIRSFR-UHFFFAOYSA-N ethyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.CCOC(=O)C=C GDCRSXZBSIRSFR-UHFFFAOYSA-N 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 235000013373 food additive Nutrition 0.000 description 2
- 239000002778 food additive Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 239000007902 hard capsule Substances 0.000 description 2
- 210000000214 mouth Anatomy 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229940127557 pharmaceutical product Drugs 0.000 description 2
- 229920000058 polyacrylate Polymers 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 150000003138 primary alcohols Chemical class 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000007901 soft capsule Substances 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- 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 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 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
- 229920003119 EUDRAGIT E PO Polymers 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- 229920003149 Eudragit® E 100 Polymers 0.000 description 1
- 229920003143 Eudragit® FS 30 D Polymers 0.000 description 1
- 229920003139 Eudragit® L 100 Polymers 0.000 description 1
- 229920003135 Eudragit® L 100-55 Polymers 0.000 description 1
- 229920003138 Eudragit® L 30 D-55 Polymers 0.000 description 1
- 229920003163 Eudragit® NE 30 D Polymers 0.000 description 1
- 229920003157 Eudragit® RL 30 D Polymers 0.000 description 1
- 229920003151 Eudragit® RL polymer Polymers 0.000 description 1
- 229920003159 Eudragit® RS 100 Polymers 0.000 description 1
- 229920003161 Eudragit® RS 30 D Polymers 0.000 description 1
- 229920003141 Eudragit® S 100 Polymers 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 239000004373 Pullulan Substances 0.000 description 1
- 229920001218 Pullulan Polymers 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 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 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
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- WGCOQYDRMPFAMN-ZDUSSCGKSA-N [(3S)-3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]-pyrimidin-5-ylmethanone Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)O[C@@H]1CN(CCC1)C(=O)C=1C=NC=NC=1 WGCOQYDRMPFAMN-ZDUSSCGKSA-N 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 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 1
- GAMPNQJDUFQVQO-UHFFFAOYSA-N acetic acid;phthalic acid Chemical compound CC(O)=O.OC(=O)C1=CC=CC=C1C(O)=O GAMPNQJDUFQVQO-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
- NEDGUIRITORSKL-UHFFFAOYSA-N butyl 2-methylprop-2-enoate;2-(dimethylamino)ethyl 2-methylprop-2-enoate;methyl 2-methylprop-2-enoate Chemical compound COC(=O)C(C)=C.CCCCOC(=O)C(C)=C.CN(C)CCOC(=O)C(C)=C NEDGUIRITORSKL-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
- 229950008138 carmellose Drugs 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 229960004515 diclofenac potassium Drugs 0.000 description 1
- KXZOIWWTXOCYKR-UHFFFAOYSA-M diclofenac potassium Chemical compound [K+].[O-]C(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl KXZOIWWTXOCYKR-UHFFFAOYSA-M 0.000 description 1
- 229960001193 diclofenac sodium Drugs 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- XPNLOZNCOBKRNJ-UHFFFAOYSA-N ethyl prop-2-enoate;methyl 2-methylprop-2-enoate Chemical compound CCOC(=O)C=C.COC(=O)C(C)=C XPNLOZNCOBKRNJ-UHFFFAOYSA-N 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229920000578 graft copolymer Polymers 0.000 description 1
- 238000010438 heat treatment Methods 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
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
- 229960003943 hypromellose Drugs 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000004898 kneading Methods 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
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- DNKKLDKIFMDAPT-UHFFFAOYSA-N n,n-dimethylmethanamine;2-methylprop-2-enoic acid Chemical compound CN(C)C.CC(=C)C(O)=O.CC(=C)C(O)=O DNKKLDKIFMDAPT-UHFFFAOYSA-N 0.000 description 1
- 229960003940 naproxen sodium Drugs 0.000 description 1
- CDBRNDSHEYLDJV-FVGYRXGTSA-M naproxen sodium Chemical compound [Na+].C1=C([C@H](C)C([O-])=O)C=CC2=CC(OC)=CC=C21 CDBRNDSHEYLDJV-FVGYRXGTSA-M 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 239000006191 orally-disintegrating tablet Substances 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940088417 precipitated calcium carbonate Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 235000019423 pullulan Nutrition 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 1
- VTGPMVCGAVZLQI-UHFFFAOYSA-M sodium;2-[4-(2-methylpropyl)phenyl]propanoate;dihydrate Chemical compound O.O.[Na+].CC(C)CC1=CC=C(C(C)C([O-])=O)C=C1 VTGPMVCGAVZLQI-UHFFFAOYSA-M 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
本発明は、酸性薬物のアルカリ金属塩の不快な味を隠蔽した経口固形組成物に関し、更に詳細には、薬物の有する苦味や粘膜刺激性等の不快味を有効に隠蔽した安定な経口固形組成物に関する。 The present invention relates to an oral solid composition that conceals the unpleasant taste of an alkali metal salt of an acidic drug, and more specifically, a stable oral solid composition that effectively conceals the unpleasant taste of the drug such as bitterness and mucosal irritation. Regarding things.
従来、酸性薬物の溶解性を向上させるため、酸性薬物をアルカリ金属塩とした活性成分が医薬品として用いられている。医薬品に使用される酸性薬物のアルカリ金属塩は、溶解性が向上されているため、服用時に口腔内で苦味や粘膜刺激性などの不快味をよりいっそう生じることが多く、このような不快味を存在は、患者の服用感を低下させるという問題があった。 Conventionally, in order to improve the solubility of an acidic drug, an active ingredient using the acidic drug as an alkali metal salt has been used as a pharmaceutical product. Alkali metal salts of acidic drugs used in pharmaceutical products often cause more unpleasant tastes such as bitterness and mucosal irritation in the oral cavity when taken because of their improved solubility. The presence had the problem of reducing the patient's feeling of taking.
そのため、酸性薬物のアルカリ金属塩の不快な味をマスキングする方法として、さまざまな物質を用いた手法が取られてきたが良好なものはなかった。特に従来薬物のマスキングに用いられていたセルロース誘導体（例えば、特許文献１〜３参照）は、酸性薬物のアルカリ金属塩と組み合わせると、薬物が安定であっても、セルロース誘導体の分解が生じるため、製剤としては不安定なものとなり、更に、不快な味もマスキングができなくなってしまった。 Therefore, as a method of masking the unpleasant taste of alkali metal salts of acidic drugs, methods using various substances have been adopted, but none of them are good. In particular, when a cellulose derivative (see, for example, Patent Documents 1 to 3) conventionally used for masking a drug is combined with an alkali metal salt of an acidic drug, the cellulose derivative is decomposed even if the drug is stable. It became unstable as a formulation, and it became impossible to mask unpleasant tastes.
従って、本発明の課題は、不快な味を有する酸性薬物のアルカリ金属塩の苦味や刺激性を低減させ、服用時に不快感を与えない安定な経口固形組成物を提供することである。 Therefore, an object of the present invention is to provide a stable oral solid composition that reduces the bitterness and irritation of an alkali metal salt of an acidic drug having an unpleasant taste and does not cause discomfort when taken.
本発明者らは、酸性薬物のアルカリ金属塩の苦味や刺激性を防ぐ方法を開発すべく、種々の材料のマスキング作用を検索していたところ、酸性薬物のアルカリ金属塩を特定の高分子化合物でマスキングすることにより、苦味や刺激性が抑制され、安定性に優れ、服用感に優れた経口組成物が得られることを見出し、本発明を完成した。 The present inventors have searched for the masking action of various materials in order to develop a method for preventing the bitterness and irritation of the alkali metal salt of the acidic drug, and found that the alkali metal salt of the acidic drug is a specific polymer compound. The present invention has been completed by finding that by masking with, an oral composition having suppressed bitterness and irritation, excellent stability, and excellent ingestion feeling can be obtained.
すなわち、本発明は、不快な味を有する酸性薬物のアルカリ金属塩と、メタアクリル系高分子化合物とを含有することを特徴とする経口固形組成物である。 That is, the present invention is an oral solid composition characterized by containing an alkali metal salt of an acidic drug having an unpleasant taste and a methacrylic polymer compound.
また、本発明は、不快な味を有する酸性薬物のアルカリ金属塩を、メタアクリル系高分子化合物で皮膜することを特徴とする経口固形組成物の製造方法である。 The present invention is also a method for producing an oral solid composition, which comprises coating an alkali metal salt of an acidic drug having an unpleasant taste with a methacrylic polymer compound.
更に、本発明は、不快な味を有する酸性薬物のアルカリ金属塩と、メタアクリル系高分子化合物とを造粒することを特徴とする経口固形組成物の製造方法である。 Furthermore, the present invention is a method for producing an oral solid composition, which comprises granulating an alkali metal salt of an acidic drug having an unpleasant taste and a methacrylic polymer compound.
また更に、本発明は、経口固形組成物中に、不快な味を有する酸性薬物のアルカリ金属塩と、メタアクリル系高分子化合物とを含有させることを特徴とする不快な味を有する酸性薬物のアルカリ金属塩の不快な味のマスキング方法である。 Furthermore, the present invention relates to an acidic drug having an unpleasant taste, which comprises containing an alkali metal salt of an acidic drug having an unpleasant taste and a methacrylic polymer compound in an oral solid composition. It is a method of masking the unpleasant taste of alkali metal salts.
本発明の経口固形組成物は、配合されるメタアクリル系高分子化合物の作用により、不快な味を有する酸性薬物のアルカリ金属塩に起因する舌を麻痺させるような強烈な苦味や粘膜刺激性を防止することができる。 The oral solid composition of the present invention has a strong bitterness and mucosal irritation that paralyzes the tongue caused by the alkali metal salt of an acidic drug having an unpleasant taste by the action of the methacrylic polymer compound to be blended. Can be prevented.
更に、経口固形組成物の安定性が良好に保たれ、従って本発明によれば、服用性に優れた薬剤を患者に提供することができる。 Furthermore, the stability of the oral solid composition is kept good, and therefore, according to the present invention, it is possible to provide a patient with a drug having excellent ingestibility.
本発明の経口固形組成物（以下、「本発明組成物」という）に用いられる、不快な味を有する酸性薬物のアルカリ金属塩（以下、単に「薬物」ということもある）は、服用時に服用者が不快感や違和感等を覚える酸性薬物のアルカリ金属塩であれば特に限定されないが、例えば、イブプロフェンナトリウム、ロキソプロフェンナトリウム、ジクロフェナクカリウム、ジクロフェナクナトリウム、ナプロキセンナトリウム等が挙げられる。これら薬物の中でも、ロキソプロフェンナトリウムが好ましい。また、これら薬物は１種または２種以上を組み合わせて用いてもよい。 The alkali metal salt of an acidic drug having an unpleasant taste (hereinafter, may be simply referred to as “drug”) used in the oral solid composition of the present invention (hereinafter, “composition of the present invention”) is taken at the time of administration. The alkali metal salt of an acidic drug that causes discomfort or discomfort to the person is not particularly limited, and examples thereof include ibuprofen sodium, loxoprofen sodium, diclofenac potassium, diclofenac sodium, and naproxen sodium. Among these drugs, loxoprofen sodium is preferable. In addition, these drugs may be used alone or in combination of two or more.
本発明組成物において、薬物の含有量は、特に制限されるものではなく各薬物の経口投与での許容投与量等に応じて適宜決定することができる。例えば、薬剤がロキソプロフェンナトリウムである場合、本発明組成物における含有量は、１〜９８質量％（以下、単に「％」という）、好ましくは２〜９０％である。 In the composition of the present invention, the content of the drug is not particularly limited and can be appropriately determined according to the permissible dose of each drug by oral administration and the like. For example, when the drug is loxoprofen sodium, the content in the composition of the present invention is 1 to 98% by mass (hereinafter, simply referred to as "%"), preferably 2 to 90%.
一方、本発明組成物において薬物の苦味や刺激性等の不快味のマスキング剤として用いられるメタクリル酸系高分子化合物としては、例えば、胃溶性メタクリル酸系高分子化合物、水不溶性メタクリル酸系高分子化合物、腸溶性メタクリル酸系高分子化合物等が挙げられる。これらメタクリル酸系高分子化合物は、１種または２種以上を組み合わせて用いてもよい。 On the other hand, examples of the methacrylic acid-based polymer compound used as a masking agent for unpleasant tastes such as bitterness and irritation of drugs in the composition of the present invention include gastrosoluble methacrylic acid-based polymer compounds and water-insoluble methacrylic acid-based polymers. Examples thereof include compounds and enteric methacrylic acid-based polymer compounds. These methacrylic acid-based polymer compounds may be used alone or in combination of two or more.
胃溶性メタクリル酸系高分子化合物としては、例えば、メタクリル酸メチル−メタクリル酸ブチル−メタクリル酸ジメチルアミノエチル共重合体（別名アミノアルキルメタクリレートコポリマーＥ：例えば、オイドラギットＥＰＯ、オイドラギットＥ１００）、メタクリル酸メチル−メタクリル酸ジエチルアミノエチル共重合体（例えば、コリコートスマートシール ３０Ｄ）等が挙げられる。 Examples of the gastrosoluble methacrylic acid-based polymer compound include methyl methacrylate-butyl methacrylate-dimethylaminoethyl methacrylate copolymer (also known as aminoalkylmethacrylate copolymer E: for example, Eudragit EPO and Eudragit E100) and methyl methacrylate-. Examples thereof include a diethylaminoethyl methacrylate copolymer (for example, Coricort Smart Seal 30D).
水不溶性メタクリル酸系高分子化合物としては、例えば、アクリル酸エチル−メタクリル酸メチル共重合体（別名アクリル酸エチル−メタクリル酸メチルコポリマー分散液：例えば、オイドラギットＮＥ３０Ｄ）、アクリル酸エチル−メタクリル酸メチル−メタクリル酸塩化トリメチルアンモニウムエチル共重合体（別名アミノアルキルメタクリレートコポリマーＲＳ：例えば、オイドラギットＲＳ１００、オイドラギットＲＳＰＯ、オイドラギットＲＬ、オイドラギットＲＬＰＯ、および別名アミノアルキルメタクリレートコポリマーＲＳ水分散液：例えば、オイドラギットＲＳ３０Ｄ、オイドラギットＲＬ３０Ｄ）等が挙げられる。 Examples of the water-insoluble methacrylic acid-based polymer compound include ethyl acrylate-methyl methacrylate copolymer (also known as ethyl acrylate-methyl methacrylate copolymer dispersion: Eudragit NE30D) and ethyl acrylate-methyl methacrylate-. Trimethylammonium Methacrylate Copolymer (also known as Aminoalkyl Methacrylate Copolymer RS: For example, Eudragit RS100, Eudragit RSPO, Eudragit RL, Eudragit RLPO, and Also known as Aminoalkyl Methacrylate Copolymer RS Aqueous Dispersion: For example, Eudragit RS30D, Eudragit RL30D) And so on.
腸溶性メタクリル酸系高分子化合物としては、例えば、メタクリル酸・アクリル酸エチル共重合体（別名メタアクリレートコポリマーＬＤ：例えば、オイドラギットＬ３０Ｄ−５５、オイドラギットＬ１００−５５）、メタクリル酸・メタクリル酸メチル共重合体（別名メタアクリレートコポリマーＬ：例えば、オイドラギットＬ１００、別名メタアクリレートコポリマーＳ：例えば、オイドラギットＳ１００）アクリル酸メチル・メタクリル酸メチル・メタクリル酸コポリマー（例えばオイドラギットＦＳ３０Ｄ）等が挙げられる。 Examples of the enteric methacrylic acid-based polymer compound include a methacrylic acid / ethyl acrylate copolymer (also known as a methacrylate copolymer LD: for example, Eudragit L30D-55, Eudragit L100-55) and a methyl methacrylate / methyl methacrylate copolymer. Examples thereof include coalescing (also known as metal acrylate copolymer L: for example, Eudragit L100, also known as methacrylate copolymer S: for example, Eudragit S100), methyl acrylate, methyl methacrylate, and methacrylate copolymer (for example, Eudragit FS30D).
本発明組成物において、メタクリル酸系高分子化合物の含有量は、メタクリル酸系高分子化合物の種類によっても異なるが、通常、薬物１００質量部に対し、０.５〜２０００質量部配合することが好ましく、１〜５００質量部配合することがより好ましく、５〜２００質量部配合することが特に好ましい。 In the composition of the present invention, the content of the methacrylic acid-based polymer compound varies depending on the type of the methacrylic acid-based polymer compound, but it is usually blended in an amount of 0.5 to 2000 parts by mass with respect to 100 parts by mass of the drug. It is preferable to blend 1 to 500 parts by mass, and particularly preferably 5 to 200 parts by mass.
なお、本発明組成物は、不快な味を有する酸性薬物のアルカリ金属塩と、メタアクリル系高分子化合物を、どのような状態であってもこれら２成分が含有さえしていればマスキング効果は得られるため、常法に従い、上記必須成分である不快な味を有する酸性薬物のアルカリ金属塩とメタクリル酸系高分子化合物とを製剤化することができる。この製剤化の際には、上記２成分のほかに通常の経口医薬品に用いられる成分を、本発明の効果を損なわない限り配合してもよい。 In addition, the composition of the present invention has a masking effect as long as it contains an alkali metal salt of an acidic drug having an unpleasant taste and a methacrylic polymer compound in any state as long as these two components are contained. Therefore, according to a conventional method, an alkali metal salt of an acidic drug having an unpleasant taste and a methacrylic acid-based polymer compound, which are the essential components, can be formulated. At the time of this formulation, in addition to the above two components, components used in ordinary oral drugs may be blended as long as the effects of the present invention are not impaired.
通常の経口医薬品に用いられる成分としては、賦形剤、可塑剤、結合剤、崩壊剤、滑沢剤、矯味剤、香料、流動改善剤、甘味剤、コーティング剤等の製剤添加剤が挙げられる。これら製剤添加剤は、薬食審査発 １２０４第１号（薬事行政法令）、医薬品添加物辞典２００７（日本医薬品添加剤協会編集、薬事日報社）および第８版食品添加物公定書（日本食品添加物協会）に記載されているものを特に制限なく用いることができる。 Ingredients used in ordinary oral medicines include excipients, plasticizers, binders, disintegrants, lubricants, flavoring agents, flavors, flow improvers, sweeteners, coating agents and other formulation additives. .. These pharmaceutical additives are listed in 1204 No. 1 (Pharmaceutical Administration Law) issued by Pharmaceutical and Food Safety Examination, Pharmaceutical Additives Dictionary 2007 (edited by Japan Pharmaceutical Additives Association, Yakuji Nippo Co., Ltd.) and 8th Edition Food Additives Official Code (Japanese Food Additives) Those described in (Food Association) can be used without particular limitation.
上記製剤添加剤のうち、賦形剤としては、例えば、乳糖、デンプン、コーンスターチ、アルファー化デンプン、部分アルファー化デンプン、結晶セルロース、低置換度ヒドロキシプロピルセルロース、ヒドロキシプロピルセルロース、精製白糖、糖アルコール類、軽質無水ケイ酸、ケイ酸カルシウム、酸化チタン、沈降炭酸カルシウム等が挙げられる。これらの賦形剤は１種または２種以上を用いることができる。 Among the above-mentioned preparation additives, examples of excipients include lactose, starch, corn starch, pregelatinized starch, partially pregelatinized starch, crystalline cellulose, low-substituted hydroxypropyl cellulose, hydroxypropyl cellulose, purified sucrose, and sugar alcohols. , Light anhydrous silicic acid, calcium silicate, titanium oxide, precipitated calcium carbonate and the like. One or more of these excipients can be used.
また、結合剤としては、例えば、ゼラチン、アラビアゴム末、メチルセルロース、カルボキシメチルセルロース、カルボキシメチルセルロースナトリウム、ヒドロキシプロピルセルロース、ヒプロメロース、ポリビニルピロリドン、ポリビニルアルコール、ポリビニルアルコール・アクリル酸・メタクリル酸メチル共重合体、ポリビニルアルコール・ポリエチレングリコール・グラフトコポリマー、プルラン、デキストリン、カルボキシメチルセルロースカルシウム、カルボキシメチルセルロースナトリウム、セラック、カルボキシビニルポリマー、カルボキシメチルスターチナトリウム、カルボキシメチルエチルセルロース、酢酸フタル酸セルロース等が挙げられる。これらの結合剤は１種または２種以上を用いることができる。 Examples of the binder include gelatin, gum arabic powder, methyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl cellulose, hypromellose, polyvinylpyrrolidone, polyvinyl alcohol, polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer, and polyvinyl. Examples thereof include alcohol / polyethylene glycol / graft copolymer, pullulan, dextrin, carboxymethyl cellulose calcium, sodium carboxymethyl cellulose, cellac, carboxyvinyl polymer, sodium carboxymethyl starch, carboxymethyl ethyl cellulose and cellulose phthalate acetate. One kind or two or more kinds of these binders can be used.
更に、崩壊剤としては、例えば、クロスカルメロースナトリウム、クロスポビドン、クロスリンクドインソルブルポリビニルピロリドン、カルメロースカルシウム、カルボキシメチルスターチナトリウム、バレイショデンプン、コーンスターチ、アルファー化デンプン等が挙げられる。これらの崩壊剤は１種または２種以上を用いることができる。 Further, examples of the disintegrant include croscarmellose sodium, crospovidone, cross-linked insolvable polyvinylpyrrolidone, carmellose calcium, sodium carboxymethyl starch, potato starch, corn starch, pregelatinized starch and the like. One or more of these disintegrants can be used.
また更に、滑沢剤としては、例えば、タルク、ステアリン酸、ステアリン酸マグネシウム、ステアリン酸カルシウム、ショ糖脂肪酸エステル類、ポリエチレングリコール等が挙げられる。これらの滑沢剤は１種または２種以上を用いることができる。 Furthermore, examples of the lubricant include talc, stearic acid, magnesium stearate, calcium stearate, sucrose fatty acid esters, polyethylene glycol and the like. One or more of these lubricants can be used.
更にまた、矯味剤としては、例えば、リンゴ酸、クエン酸、酒石酸などを挙げることができる。 Furthermore, examples of the flavoring agent include malic acid, citric acid, tartaric acid and the like.
なお、本発明組成物の製剤化においては、不快な味を有する酸性薬物のアルカリ金属塩にメタアクリル系高分子化合物の皮膜を施したもの、または不快な味を有する酸性薬物のアルカリ金属塩とメタアクリル系高分子化合物とを造粒したものを利用することにより、単にこれら２成分を含有する場合よりも、マスキング効果が高まるので好ましい。 In the formulation of the composition of the present invention, an alkali metal salt of an acidic drug having an unpleasant taste is coated with a film of a methacrylic polymer compound, or an alkali metal salt of an acidic drug having an unpleasant taste. It is preferable to use a granulated product of a metal acrylic polymer compound because the masking effect is enhanced as compared with the case where these two components are simply contained.
不快な味を有する酸性薬物のアルカリ金属塩にメタアクリル系高分子化合物の皮膜を施すには、不快な味を有する酸性薬物のアルカリ金属塩を、メタアクリル系高分子化合物で被覆すればよい。 In order to apply a film of the methacrylic polymer compound to the alkali metal salt of the acidic drug having an unpleasant taste, the alkali metal salt of the acidic drug having an unpleasant taste may be coated with the methacrylic polymer compound.
本発明組成物の製剤化において、不快な味を有する酸性薬物のアルカリ金属塩を、メタアクリル系高分子化合物で被覆したものを利用する場合、例えば、薬物および必要に応じて任意成分を混合・造粒・乾燥・整粒し、得られた粉粒物に、水または低級アルコールおよび両者の混合水溶液等適切な溶媒で溶解または分散したメタアクリル系高分子化合物を流動層中で噴霧し、皮膜を施す方法等を挙げることができる。 In the formulation of the composition of the present invention, when an alkali metal salt of an acidic drug having an unpleasant taste is coated with a methacrylic polymer compound, for example, the drug and an arbitrary component are mixed as necessary. A methacrylic polymer compound dissolved or dispersed in an appropriate solvent such as water or a lower alcohol and a mixed aqueous solution of both is sprayed on the obtained powder or granules after granulation, drying and sizing in a fluidized layer to form a film. The method of applying the above can be mentioned.
なお、低級アルコールとしては、エタノール、イソプロパノール等のＣ２〜３の第１級アルコールを使用することができる。複数のメタアクリル系高分子化合物を用いる場合は、これらを併せて溶媒に溶解または分散させ噴霧してもよく、または、各メタアクリル系高分子化合物をそれぞれ単独で溶媒に溶解または分散させ、複数回に分けて噴霧を行ってもよい。 As the lower alcohol, C 2-3 primary alcohols such as ethanol and isopropanol can be used. When a plurality of methacrylic polymer compounds are used, they may be dissolved or dispersed in a solvent together and sprayed, or each methacrylic polymer compound may be independently dissolved or dispersed in a solvent to obtain a plurality. Spraying may be performed in batches.
また、本発明組成物の製剤化において、不快な味を有する酸性薬物のアルカリ金属塩とメタアクリル系高分子化合物とを造粒したものを利用する場合、例えば、薬物および必要に応じて任意成分を混合し、この混合物に、水または低級アルコールおよび両者の混合水溶液等適切な溶媒で溶解または分散した高分子化合物を添加し、これを高速撹拌造粒法、流動層造粒法等の公知の造粒方法に従って造粒する方法、薬物および高分子化合物並びに必要に応じて任意成分を混合し、この混合物を２軸エクストルーダ−等のエクストルーダ−を用いて、混合・混練・加圧・加熱・冷却・押出し、造粒する方法等を挙げることができる。 Further, in the formulation of the composition of the present invention, when a mixture of an alkali metal salt of an acidic drug having an unpleasant taste and a methacrylic polymer compound is used, for example, a drug and an optional component if necessary. To this mixture, a polymer compound dissolved or dispersed in an appropriate solvent such as water or a lower alcohol and a mixed aqueous solution of both is added, and this is known as a high-speed stirring granulation method, a fluidized layer granulation method, or the like. A method of granulating according to a granulation method, a drug and a polymer compound, and if necessary, an arbitrary component is mixed, and this mixture is mixed, kneaded, pressurized, heated, and cooled using an extruder such as a twin-screw extruder. -The method of extruding and granulating can be mentioned.
なお、低級アルコールとしては、エタノール、イソプロパノール等のＣ２〜３の第１級アルコールを使用することができる。複数の高分子を用いる場合は、これらを併せて溶媒に溶解または分散させ造粒してもよく、または、各高分子をそれぞれ単独で溶媒に溶解または分散させ、複数回に分けて造粒を行ってもよい。 As the lower alcohol may be used ethanol, the primary alcohols of C 2 ~ 3 of isopropanol. When a plurality of polymers are used, they may be dissolved or dispersed in a solvent together for granulation, or each polymer may be individually dissolved or dispersed in a solvent and granulated in a plurality of times. You may go.
更に、本発明組成物の製剤化においては、不快な味を有する酸性薬物のアルカリ金属塩にメタアクリル系高分子化合物の皮膜を施したものと、不快な味を有する酸性薬物のアルカリ金属塩とメタアクリル系高分子化合物とを造粒したものを組み合わせたものも利用できる。 Further, in the formulation of the composition of the present invention, an alkali metal salt of an acidic drug having an unpleasant taste is coated with a film of a methacrylic polymer compound, and an alkali metal salt of an acidic drug having an unpleasant taste. A combination of granulated metal acrylic polymer compounds can also be used.
上記方法としては、例えば、薬物と必要に応じて任意成分を混合し、この混合物に、水または低級アルコールおよび両者の混合水溶液等適切な溶媒で溶解または分散したメタアクリル系高分子化合物を添加し、これを高速撹拌造粒法、流動層造粒法等の公知の造粒方法に従って造粒するか、薬物および高分子化合物並びに必要に応じて任意成分を混合し、この混合物を２軸エクストルーダ−等のエクストルーダーを用いて、混合・混練・加圧・加熱・冷却・押出し、造粒して得られた造粒物に、水または低級アルコールおよび両者の混合水溶液等適切な溶媒で溶解または分散したメタアクリル系高分子化合物を流動層中で噴霧し、皮膜を施す方法等を挙げることができる。 As the above method, for example, a drug and an arbitrary component are mixed as necessary, and a methacrylic polymer compound dissolved or dispersed in an appropriate solvent such as water or a lower alcohol and a mixed aqueous solution of both is added to the mixture. , This is granulated according to a known granulation method such as a high-speed stirring granulation method or a fluidized layer granulation method, or a drug and a polymer compound and an optional component are mixed as necessary, and this mixture is mixed with a biaxial extruder. Dissolve or disperse in a granulated product obtained by mixing, kneading, pressurizing, heating, cooling, extruding, and granulating using an extruder such as water or a lower alcohol and an appropriate solvent such as a mixed aqueous solution of both. Examples thereof include a method of spraying a methacrylic polymer compound in a fluidized layer to form a film.
斯くして製剤化された本発明組成物は、そのままでもよいが、必要に応じて、篩分け等により整粒して顆粒とすることもできる。この顆粒の粒子径は、平均粒子径が２０〜１０００μｍ程度であり、好ましくは５０〜７００μｍである。なお、顆粒の平均粒子径は、質量・体積分布により測定される値である。 The composition of the present invention thus formulated may be used as it is, but may be sized into granules by sieving or the like, if necessary. The average particle size of the granules is about 20 to 1000 μm, preferably 50 to 700 μm. The average particle size of the granules is a value measured by mass / volume distribution.
また、本発明組成物は、必要に応じて、種々の剤形にすることができ、例えば、上記で得られた顆粒を、常法に従って、分包し分包顆粒剤として、カプセルに充填し硬カプセル剤または軟カプセル剤として、あるいは、打錠することにより錠剤として調製することができる。これら、分包顆粒剤、硬カプセル剤、軟カプセル剤、錠剤を調製する際には、必要に応じて、更に、上記した製剤添加剤を加えることもできる。 In addition, the composition of the present invention can be made into various dosage forms as needed. For example, the granules obtained above are packaged according to a conventional method and filled into capsules as a packaged granule. It can be prepared as a hard capsule or a soft capsule, or as a tablet by tableting. When preparing these packaged granules, hard capsules, soft capsules, and tablets, the above-mentioned formulation additives can be further added, if necessary.
本発明組成物は、上記剤形の中でも錠剤とすることが好ましい。錠剤は、例えば、上記で造粒された顆粒および必要により加えた充填粉末成分を、単発式打錠機、ロータリー式打錠機等を用いて圧縮成型することにより製造することができる。このときの圧縮成型時の圧力は、１〜１１０ＫＮが好ましく、より好ましくは２〜９０ＫＮである。また、打錠後の錠剤は、その直径が、約７〜１５ｍｍ程度の丸型錠剤の服用しやすいものとすることが好ましい。 The composition of the present invention is preferably a tablet among the above dosage forms. Tablets can be produced, for example, by compression-molding the granules granulated above and the filling powder component added as necessary using a single-shot tableting machine, a rotary tableting machine, or the like. The pressure during compression molding at this time is preferably 1 to 110 KN, more preferably 2 to 90 KN. Further, it is preferable that the tablet after tableting is easy to take as a round tablet having a diameter of about 7 to 15 mm.
このようにして製造された本発明組成物を含有する顆粒、カプセル剤、錠剤は、製造コストも低く、加工し易いものであり、さらには、不快な味を有する酸性薬物のアルカリ金属塩を含有するものの、これと組み合わせて配合される高分子化合物のために、苦味や収斂味が抑制され、服用感に優れたものである。そのうえ、安定性も優れている。 The granules, capsules, and tablets containing the composition of the present invention thus produced are low in production cost, easy to process, and further contain an alkali metal salt of an acidic drug having an unpleasant taste. However, because of the polymer compound blended in combination with this, bitterness and astringent taste are suppressed, and the feeling of ingestion is excellent. Besides, it is also excellent in stability.
以上説明した本発明組成物の特に好ましい態様としては、下記に示す組成物を挙げることができる。
酸性薬物のアルカリ金属塩 １５〜９０％
メタアクリル系高分子化合物 １〜５０％
As a particularly preferable embodiment of the composition of the present invention described above, the composition shown below can be mentioned.
Alkali metal salts of acidic drugs 15-90%
Metallic polymer compound 1-50%
次に、実施例および比較例を示し、本発明をさらに具体的に説明するが、本発明はこれらに何ら制約されるものではない。 Next, Examples and Comparative Examples will be shown and the present invention will be described in more detail, but the present invention is not limited thereto.
実 施 例 １
＜発明品１＞
ロキソプロフェンナトリウム水和物６８１ｇ、結晶セルロース８５ｇ（旭化成ケミカルズ社製）、低置換度ヒドロキシプロピルセルロース２００ｇ、軽質無水ケイ酸２０ｇ、ポリビニルアルコール（部分けん化物）１４ｇを高速攪拌式混合造粒機を用いて混合した。この混合物に精製水１００ｇを添加し、造粒した。続いて、造粒物を流動層乾燥機を用いて乾燥し、整粒機を用いて整粒し、平均粒子径が３８０μｍの顆粒を得た。この乾燥顆粒２００ｇを取り、流動層中でメタクリル酸メチル・メタクリル酸ジエチルアミノエチル共重合体分散液（固形分３０％）４８８ｇ、クエン酸トリエチル２２.２ｇ、軽質無水ケイ酸７.２ｇ、カルボキシメチルセルロースナトリウム４.２ｇ、精製水３７８.４ｇを均一に混合したコーティング液を顆粒の質量増が４０％になるまで噴霧して被覆核粒子である発明品１を得た。
Example 1
<Invention 1>
Loxoprofen sodium hydrate 681 g, crystalline cellulose 85 g (manufactured by Asahi Kasei Chemicals Co., Ltd.), low-substituted hydroxypropyl cellulose 200 g, light anhydrous silicic acid 20 g, polyvinyl alcohol (partially saponified product) 14 g using a high-speed stirring mixing granulator. Mixed. 100 g of purified water was added to this mixture for granulation. Subsequently, the granules were dried using a fluidized bed dryer and sized using a sizing machine to obtain granules having an average particle diameter of 380 μm. Take 200 g of these dried granules, and in a fluidized bed, 488 g of a copolymer dispersion of methyl methacrylate and diethylaminoethyl methacrylate (solid content 30%), 22.2 g of triethyl citrate, 7.2 g of light anhydrous silicic acid, and sodium carboxymethyl cellulose. A coating solution obtained by uniformly mixing 4.2 g and 378.4 g of purified water was sprayed until the mass increase of the granules reached 40% to obtain Invention 1 which is a coated nucleus particle.
＜発明品２＞
発明品１と同様にしてメタクリル酸メチル・メタクリル酸ジエチルアミノエチル共重合体分散液（固形分３０％）４８８ｇ、クエン酸トリエチル２２.２ｇ、軽質無水ケイ酸７.２ｇ、カルボキシメチルセルロースナトリウム４.２ｇ、精製水３７８.４ｇを均一に混合したコーティング液を顆粒の質量増が３０％になるまで噴霧して被覆核粒子である発明品２を得た。
<Invention 2>
Similar to Invention 1, 488 g of methyl methacrylate / diethylaminoethyl methacrylate copolymer dispersion (solid content 30%), 22.2 g of triethyl citrate, 7.2 g of light anhydrous silicic acid, 4.2 g of sodium carboxymethyl cellulose, A coating solution in which 378.4 g of purified water was uniformly mixed was sprayed until the mass increase of the granules reached 30% to obtain Invention 2 as coated nuclei particles.
＜発明品３＞
発明品１と同様にしてメタクリル酸メチル・メタクリル酸ジエチルアミノエチル共重合体分散液（固形分３０％）４８８ｇ、クエン酸トリエチル２２.２ｇ、軽質無水ケイ酸７.２ｇ、カルボキシメチルセルロースナトリウム４.２ｇ、精製水３７８.４ｇを均一に混合したコーティング液を顆粒の質量増が２０％になるまで噴霧して被覆核粒子である発明品３を得た。
<Invention 3>
Similar to Invention 1, 488 g of methyl methacrylate / diethylaminoethyl methacrylate copolymer dispersion (solid content 30%), 22.2 g of triethyl citrate, 7.2 g of light anhydrous silicic acid, 4.2 g of sodium carboxymethyl cellulose, A coating solution in which 378.4 g of purified water was uniformly mixed was sprayed until the mass increase of the granules reached 20% to obtain Invention 3 which is a coated nucleus particle.
実 施 例 ２
＜発明品４＞
ロキソプロフェンナトリウム水和物６８.１ｇ、結晶セルロース３０ｇ、乳糖８１.９ｇを高速攪拌式混合造粒機を用いて混合した。この混合物にメタクリル酸メチル・メタクリル酸ジエチルアミノエチル共重合体分散液（固形分３０％）６５.７ｇ、クエン酸トリエチル０.３ｇの混合水溶液を数回に分けて添加し、造粒した。続いて、この造粒物を棚型乾燥機で乾燥し、整粒機を用いて整粒し、平均粒子径が４１７μｍの造粒物である発明品４を得た。
Example 2
<Invention 4>
68.1 g of loxoprofen sodium hydrate, 30 g of crystalline cellulose, and 81.9 g of lactose were mixed using a high-speed stirring type mixing granulator. A mixed aqueous solution of 65.7 g of a copolymer dispersion of methyl methacrylate and diethylaminoethyl methacrylate (solid content: 30%) and 0.3 g of triethyl citrate was added to this mixture in several portions to granulate. Subsequently, this granulated product was dried with a shelf-type dryer and sized using a sizing machine to obtain Invention 4 which is a granulated product having an average particle diameter of 417 μm.
比 較 例 １
＜比較品１＞
ロキソプロフェンナトリウム水和物６８１ｇ、結晶セルロース８５ｇ（旭化成ケミカルズ社製）、低置換度ヒドロキシプロピルセルロース２００ｇ、軽質無水ケイ酸２０ｇ、ポリビニルアルコール（部分けん化物）１４ｇを高速攪拌式混合造粒機を用いて混合した。この混合物に精製水１００ｇを添加し、造粒した。続いて、造粒物を流動層乾燥機を用いて乾燥し、整粒機を用いて整粒し、比較品１を得た。
Comparison example 1
<Comparison product 1>
Loxoprofen sodium hydrate 681 g, crystalline cellulose 85 g (manufactured by Asahi Kasei Chemicals Co., Ltd.), low-substituted hydroxypropyl cellulose 200 g, light anhydrous silicic acid 20 g, polyvinyl alcohol (partially saponified product) 14 g using a high-speed stirring mixing granulator. Mixed. 100 g of purified water was added to this mixture for granulation. Subsequently, the granulated product was dried using a fluidized bed dryer and sized using a sizing machine to obtain Comparative Product 1.
比 較 品 ２
＜比較品２＞
ロキソプロフェンナトリウム水和物６８.１ｇ、結晶セルロース３０ｇ、乳糖８１.９ｇヒドロキシプロピルセルロース２０ｇを高速攪拌式混合造粒機を用いて混合した。この混合物に精製水１０ｇを数回に分けて添加し、造粒した。続いて、この造粒物を棚型乾燥機で乾燥し、整粒機を用いて整粒し、比較品２を得た。
Comparative product 2
<Comparison product 2>
68.1 g of loxoprofen sodium hydrate, 30 g of crystalline cellulose, and 81.9 g of lactose and 20 g of hydroxypropyl cellulose were mixed using a high-speed stirring type mixing granulator. 10 g of purified water was added to this mixture in several portions to granulate. Subsequently, this granulated product was dried with a shelf-type dryer and sized using a sizing machine to obtain Comparative Product 2.
試 験 例 １
発明品１〜４、比較品１および２について、被験者５名を用い、不快な味の官能試験をそれぞれ下記マスキング評価基準に従って行った。それぞれの平均結果を併せて表１に示す。
Trial example 1
For Inventions 1 to 4 and Comparative Products 1 and 2, five subjects were used to perform a sensory test of unpleasant taste according to the following masking evaluation criteria. Table 1 shows the average results of each.
＜マスキング評価基準＞
（評点） （内容）
４点 ： マスキング効果が非常にある
３点 ： マスキング効果がある
２点 ： マスキング効果が少しある
１点 ： マスキング効果が僅かにある
０点 ： マスキング効果が全く無い
<Masking evaluation criteria>
(Score) (Content)
4 points: Very masking effect 3 points: Masking effect 2 points: Slight masking effect 1 point: Slight masking effect 0 points: No masking effect at all
表１の発明品１〜４の結果より、メタアクリル系高分子化合物を配合することにより、被覆核粒子および造粒物が安定になり、酸性薬物のアルカリ金属塩の不快な味を改善することが分かった。 From the results of Inventions 1 to 4 in Table 1, by blending the methacrylic polymer compound, the coated nucleus particles and the granulated product are stabilized, and the unpleasant taste of the alkali metal salt of the acidic drug is improved. I found out.
実 施 例 ３
分包顆粒：
実施例１で得た発明品１の被覆核粒子１２０ｇ、乳糖２００ｇ、トウモロコシデンプン１７７.５ｇ、アセスルファムカリウム０.５ｇ、アスパルテーム０.５ｇ、香料０.５ｇ、軽質無水ケイ酸０.５ｇ、タルク０.５ｇ、ステアリン酸マグネシウム０.５ｇを均一に混合し、１包あたり５００ｍｇとようにアルミヒートシールで分包して、ロキソプロフェンナトリウム水和物６８.１ｍｇを含有する分包顆粒を得た。
Actual example 3
Packaged granules:
120 g of coated nucleus particles of Invention 1 obtained in Example 1, 200 g of lactose, 177.5 g of corn starch, 0.5 g of acesulfame potassium, 0.5 g of aspartame, 0.5 g of fragrance, 0.5 g of light anhydrous silicic acid, 0 talc 0.5 g and 0.5 g of magnesium stearate were uniformly mixed and packaged with an aluminum heat seal so as to be 500 mg per packet to obtain packaged granules containing 68.1 mg of loxoprofen sodium hydrate.
実 施 例 ４
口腔内崩壊錠：
実施例１で得た発明品２の被覆核粒子１３０ｇ、結晶セルロース１５５.６ｇ、トウモロコシデンプン１００ｇ、アセスルファムカリウム４ｇ、アスパルテーム４ｇ、香料０.４ｇ、軽質無水ケイ酸２ｇ、タルク２ｇ、ステアリン酸マグネシウム２ｇを均一に混合し、質量６００ｍｇになるように、直径１２ｍｍφの臼杵でロータリー式打錠機を用いて圧縮成型し、ロキソプロフェンナトリウム水和物６８.１ｍｇを含有する厚さ約４.７ｍｍの口腔内崩壊錠を得た。
Example 4
Orally disintegrating lock:
130 g of coated core particles of Invention 2 obtained in Example 1, 155.6 g of crystalline cellulose, 100 g of corn starch, 4 g of acesulfame potassium, 4 g of aspartame, 0.4 g of fragrance, 2 g of light anhydrous silicic acid, 2 g of talc, 2 g of magnesium stearate. Is uniformly mixed and compression-molded using a rotary tableting machine with a mortar having a diameter of 12 mmφ so as to have a mass of 600 mg. In the oral cavity having a thickness of about 4.7 mm containing 68.1 mg of loxoprofen sodium hydrate. Obtained a disintegrating tablet.
実 施 例 ５
口腔内崩壊錠：
実施例１で得た発明品３の被覆核粒子１４０ｇ、結晶セルロース１５５.６ｇ、デンプン６０ｇ、マンニトール３０ｇ、アセスルファムカリウム４ｇ、アスパルテーム４ｇ、香料０.４ｇ、軽質無水ケイ酸２ｇ、タルク２ｇ、ステアリン酸マグネシウム２ｇを均一に混合し、質量６００ｍｇになるように、直径１２ｍｍφの臼杵でロータリー式打錠機を用いて圧縮成型し、ロキソプロフェンナトリウム水和物６８.１ｍｇを含有する厚さ約４.７ｍｍの口腔内崩壊錠を得た。
Example 5
Orally disintegrating lock:
140 g of coated core particles of Invention 3 obtained in Example 1, 155.6 g of crystalline cellulose, 60 g of starch, 30 g of mannitol, 4 g of acesulfame potassium, 4 g of aspartame, 0.4 g of fragrance, 2 g of light anhydrous silicic acid, 2 g of talc, stearic acid. 2 g of magnesium is uniformly mixed and compression-molded using a rotary tableting machine with a knitol having a diameter of 12 mmφ so as to have a mass of 600 mg, and a thickness of about 4.7 mm containing 68.1 mg of loxoprofene sodium hydrate is contained. An orally disintegrating tablet was obtained.
実 施 例 ６
分包顆粒：
実施例２で得た発明品４の被覆核粒子１２０ｇ、乳糖２００ｇ、トウモロコシデンプン１７７.５ｇ、アセスルファムカリウム０.５ｇ、アスパルテーム０.５ｇ、香料０.５ｇ、軽質無水ケイ酸０.５ｇ、タルク０.５ｇ、ステアリン酸マグネシウム０.５ｇを均一に混合し、１包あたり５００ｍｇとようにアルミヒートシールで分包して分包顆粒を得た。
Example 6
Packaged granules:
120 g of coated nucleus particles of Invention 4 obtained in Example 2, 200 g of lactose, 177.5 g of corn starch, 0.5 g of acesulfame potassium, 0.5 g of aspartame, 0.5 g of fragrance, 0.5 g of light anhydrous silicic acid, 0 talc 0.5 g and 0.5 g of magnesium stearate were uniformly mixed and packaged with an aluminum heat seal so as to be 500 mg per packet to obtain packaged granules.
本発明の経口組成物は、不快な味を有する薬物の苦味や収斂味が防止され、服用感に優れているので不快な味を有する薬物を有効成分とする各種薬剤等に好適に利用することができる。
以 上
Since the oral composition of the present invention prevents the bitterness and astringent taste of a drug having an unpleasant taste and is excellent in ingestion, it is preferably used for various drugs containing a drug having an unpleasant taste as an active ingredient. Can be done.
that's all
Claims (9)
前記不快な味を有する酸性薬物のアルカリ金属塩が、ロキソプロフェンナトリウムであり、
前記メタアクリル系高分子化合物が、メタクリル酸メチル−メタクリル酸ジエチルアミノエチル共重合体である、
ことを特徴とする経口固形組成物。 Contains an alkali metal salt of an acidic drug having an unpleasant taste and a methacrylic polymer compound,
The alkali metal salt of the acidic drug having an unpleasant taste is loxoprofen sodium.
The methacrylic acid-based polymer compound is a methyl methacrylate-diethylaminoethyl methacrylate copolymer.
An oral solid composition characterized by that.
前記不快な味を有する酸性薬物のアルカリ金属塩が、ロキソプロフェンナトリウムであり、
前記メタアクリル系高分子化合物が、メタクリル酸メチル−メタクリル酸ジエチルアミノエチル共重合体である、
ことを特徴とする経口固形組成物の製造方法。 A method for producing an oral solid composition in which an alkali metal salt of an acidic drug having an unpleasant taste is coated with a methacrylic polymer compound.
The alkali metal salt of the acidic drug having an unpleasant taste is loxoprofen sodium.
The methacrylic acid-based polymer compound is a methyl methacrylate-diethylaminoethyl methacrylate copolymer.
A method for producing an oral solid composition.
前記不快な味を有する酸性薬物のアルカリ金属塩が、ロキソプロフェンナトリウムであり、
前記メタアクリル系高分子化合物が、メタクリル酸メチル−メタクリル酸ジエチルアミノエチル共重合体である、
ことを特徴とする経口固形組成物の製造方法。 A method for producing an oral solid composition for granulating an alkali metal salt of an acidic drug having an unpleasant taste and a methacrylic polymer compound.
The alkali metal salt of the acidic drug having an unpleasant taste is loxoprofen sodium.
The methacrylic acid-based polymer compound is a methyl methacrylate-diethylaminoethyl methacrylate copolymer.
A method for producing an oral solid composition.
前記不快な味を有する酸性薬物のアルカリ金属塩が、ロキソプロフェンナトリウムであり、
前記メタアクリル系高分子化合物が、メタクリル酸メチル−メタクリル酸ジエチルアミノエチル共重合体である、
ことを特徴とする不快な味を有する酸性薬物のアルカリ金属塩の不快な味のマスキング方法。 It is a method for masking the unpleasant taste of an alkaline metal salt of an acidic drug having an unpleasant taste and containing a methacrylic polymer compound in the oral solid composition. hand,
The alkali metal salt of the acidic drug having an unpleasant taste is loxoprofen sodium.
The methacrylic acid-based polymer compound is a methyl methacrylate-diethylaminoethyl methacrylate copolymer.
A method of masking the unpleasant taste of an alkali metal salt of an acidic drug having an unpleasant taste.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2015255829A JP6812104B2 (en) | 2015-12-28 | 2015-12-28 | Oral solid composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2015255829A JP6812104B2 (en) | 2015-12-28 | 2015-12-28 | Oral solid composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2017119632A JP2017119632A (en) | 2017-07-06 |
| JP6812104B2 true JP6812104B2 (en) | 2021-01-13 |
Family
ID=59271442
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015255829A Active JP6812104B2 (en) | 2015-12-28 | 2015-12-28 | Oral solid composition |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP6812104B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20200028108A1 (en) | 2017-03-29 | 2020-01-23 | Hitachi Chemical Company, Ltd. | Charge transport material and use of same |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6144811A (en) * | 1984-08-10 | 1986-03-04 | Ss Pharmaceut Co Ltd | Sustained release diclofenac sodium pharmaceutical |
| US5075114A (en) * | 1990-05-23 | 1991-12-24 | Mcneil-Ppc, Inc. | Taste masking and sustained release coatings for pharmaceuticals |
| JP2849047B2 (en) * | 1994-12-19 | 1999-01-20 | 大正薬品工業株式会社 | Diclofenac sodium sustained-release preparation and its production method |
| JP5405752B2 (en) * | 2007-01-31 | 2014-02-05 | 大日本住友製薬株式会社 | Coated drug-containing particles and solid preparation containing the particles |
| JP5845173B2 (en) * | 2009-05-01 | 2016-01-20 | アデア ファーマスーティカルズ，インコーポレイテッド | Orally disintegrating tablet composition comprising a combination of a non-opioid and an opioid analgesic |
| JP2012528819A (en) * | 2009-06-04 | 2012-11-15 | ビーエーエスエフ ソシエタス・ヨーロピア | Orally disintegrating dosage form containing taste mask active ingredient |
| JP5680898B2 (en) * | 2010-08-10 | 2015-03-04 | 京都薬品工業株式会社 | Fast disintegrating tablets with reduced bitterness |
| JP5664225B2 (en) * | 2010-12-28 | 2015-02-04 | ライオン株式会社 | Unpleasant taste masking particles and oral preparations containing the same |
| JP6018911B2 (en) * | 2012-12-27 | 2016-11-02 | ライオン株式会社 | Granules, capsules |
| JP5619970B2 (en) * | 2013-08-05 | 2014-11-05 | 大原薬品工業株式会社 | Method for producing bioactive substance-containing particles |
-
2015
- 2015-12-28 JP JP2015255829A patent/JP6812104B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| JP2017119632A (en) | 2017-07-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5752227B2 (en) | Orally disintegrating tablets | |
| MX2007015377A (en) | An entacapone-containing oral dosage form. | |
| WO2011019043A1 (en) | Tablet that disintegrates rapidly in the mouth and that contains two or more types of particles | |
| JP7361833B2 (en) | Orally disintegrating tablet of 2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methylthiazole-5-carboxylic acid | |
| JP6768984B2 (en) | Zinc acetate hydrate tablet and its manufacturing method | |
| WO2012029838A1 (en) | Orally disintegrating tablet | |
| JP6812104B2 (en) | Oral solid composition | |
| JP7066351B2 (en) | Levodopa-containing miniaturized tablets with good sustained release | |
| JP2018083809A (en) | Production method of silodosin-containing particles and production method of orally disintegrating tablet containing silodosin | |
| JP5275815B2 (en) | Orally disintegrating tablets and bitterness-suppressing preparations containing risperidone | |
| JP6538321B2 (en) | Oral composition | |
| JP5978335B2 (en) | Irbesartan-containing pharmaceutical composition with good dissolution and orally disintegrating tablet | |
| JP6866153B2 (en) | Compression molding formulation | |
| JP6855387B2 (en) | Compression molding formulation | |
| JP7377943B2 (en) | Method for manufacturing solid preparations | |
| JP7308022B2 (en) | Orally disintegrating tablet with suppressed bitterness of fast-dissolving drug | |
| JP7023186B2 (en) | Orally disintegrating tablets containing dementia treatment | |
| JP5919173B2 (en) | Sustained release ambroxol hydrochloride orally disintegrating tablets | |
| JP6847190B2 (en) | Orally disintegrating tablets with improved ease of administration containing granules containing a flavoring agent | |
| JP6618595B1 (en) | Caffeine and hyoscyamine-containing pharmaceutical composition and method for producing the same | |
| JP7407364B2 (en) | Ramelteon-containing solid preparation | |
| JP6150564B2 (en) | Orally rapidly disintegrating tablets | |
| CN115803020A (en) | Orally disintegrating tablet containing milobalin besylate | |
| WO2019098327A1 (en) | Orally disintegrating tablet having suppressed bitterness of fast dissolving drug |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| RD01 | Notification of change of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7426 Effective date: 20161221 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20181219 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20190828 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190903 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20191031 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200331 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20200601 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200710 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20200710 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20201124 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20201216 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6812104 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |