TR201801726T4 - Rasekadotri̇l ve farmasöti̇k bi̇leşi̇mleri̇. - Google Patents
Rasekadotri̇l ve farmasöti̇k bi̇leşi̇mleri̇. Download PDFInfo
- Publication number
- TR201801726T4 TR201801726T4 TR2018/01726T TR201801726T TR201801726T4 TR 201801726 T4 TR201801726 T4 TR 201801726T4 TR 2018/01726 T TR2018/01726 T TR 2018/01726T TR 201801726 T TR201801726 T TR 201801726T TR 201801726 T4 TR201801726 T4 TR 201801726T4
- Authority
- TR
- Turkey
- Prior art keywords
- racecadotril
- disperse
- tablets
- taste
- masked
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title abstract description 3
- 238000000034 method Methods 0.000 claims abstract description 11
- 238000005550 wet granulation Methods 0.000 claims abstract description 8
- ODUOJXZPIYUATO-UHFFFAOYSA-N 2-[[2-[(acetylthio)methyl]-1-oxo-3-phenylpropyl]amino]acetic acid (phenylmethyl) ester Chemical compound C=1C=CC=CC=1COC(=O)CNC(=O)C(CSC(=O)C)CC1=CC=CC=C1 ODUOJXZPIYUATO-UHFFFAOYSA-N 0.000 claims description 37
- 229960002281 racecadotril Drugs 0.000 claims description 36
- 108700040249 racecadotril Proteins 0.000 claims description 36
- 229920001577 copolymer Polymers 0.000 claims description 12
- 235000019640 taste Nutrition 0.000 claims description 11
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 9
- 229930195725 Mannitol Natural products 0.000 claims description 9
- 239000000594 mannitol Substances 0.000 claims description 9
- 235000010355 mannitol Nutrition 0.000 claims description 9
- 229920000881 Modified starch Polymers 0.000 claims description 7
- 108010011485 Aspartame Proteins 0.000 claims description 6
- 239000000605 aspartame Substances 0.000 claims description 6
- 235000010357 aspartame Nutrition 0.000 claims description 6
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 6
- 229960003438 aspartame Drugs 0.000 claims description 6
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims description 6
- 235000003599 food sweetener Nutrition 0.000 claims description 6
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims description 6
- 239000003765 sweetening agent Substances 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 claims description 3
- 239000000619 acesulfame-K Substances 0.000 claims description 3
- 235000010358 acesulfame potassium Nutrition 0.000 claims description 2
- 229960004998 acesulfame potassium Drugs 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 229960000913 crospovidone Drugs 0.000 claims description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims 1
- 206010012735 Diarrhoea Diseases 0.000 abstract description 3
- 239000003826 tablet Substances 0.000 description 26
- LQIAZOCLNBBZQK-UHFFFAOYSA-N 1-(1,2-Diphosphanylethyl)pyrrolidin-2-one Chemical compound PCC(P)N1CCCC1=O LQIAZOCLNBBZQK-UHFFFAOYSA-N 0.000 description 8
- 239000006185 dispersion Substances 0.000 description 8
- 239000008187 granular material Substances 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 241000220223 Fragaria Species 0.000 description 6
- 235000016623 Fragaria vesca Nutrition 0.000 description 6
- 235000011363 Fragaria x ananassa Nutrition 0.000 description 6
- 229920000642 polymer Polymers 0.000 description 6
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 5
- 229920003085 Kollidon® CL Polymers 0.000 description 5
- 239000000796 flavoring agent Substances 0.000 description 5
- 235000019634 flavors Nutrition 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 230000000873 masking effect Effects 0.000 description 5
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 229920003163 Eudragit® NE 30 D Polymers 0.000 description 4
- -1 Racecadotril compound Chemical class 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 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 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
- 229920000058 polyacrylate Polymers 0.000 description 3
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000007919 dispersible tablet Substances 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 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 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical class CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229940127557 pharmaceutical product Drugs 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229940069328 povidone Drugs 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000007916 tablet composition Substances 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- KVHQNWGLVVERFR-ACMTZBLWSA-N (3s)-3-amino-4-[[(2s)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoic acid;6-methyl-2,2-dioxooxathiazin-4-one Chemical compound CC1=CC(=O)[NH2+]S(=O)(=O)O1.[O-]C(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 KVHQNWGLVVERFR-ACMTZBLWSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 229920002126 Acrylic acid copolymer Polymers 0.000 description 1
- 229910002012 Aerosil® Inorganic materials 0.000 description 1
- 244000144730 Amygdalus persica Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 229920003119 EUDRAGIT E PO Polymers 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 229920003149 Eudragit® E 100 Polymers 0.000 description 1
- 229920003153 Eudragit® NE polymer Polymers 0.000 description 1
- 229920003151 Eudragit® RL polymer Polymers 0.000 description 1
- 229920003152 Eudragit® RS polymer Polymers 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920001479 Hydroxyethyl methyl cellulose Polymers 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- 240000008790 Musa x paradisiaca Species 0.000 description 1
- 235000018290 Musa x paradisiaca Nutrition 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 235000006040 Prunus persica var persica Nutrition 0.000 description 1
- 235000011034 Rubus glaucus Nutrition 0.000 description 1
- 244000235659 Rubus idaeus Species 0.000 description 1
- 235000009122 Rubus idaeus Nutrition 0.000 description 1
- WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical compound [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 239000004376 Sucralose Substances 0.000 description 1
- 208000025371 Taste disease Diseases 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 239000013543 active substance Substances 0.000 description 1
- 229960001504 aspartame acesulfame Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 239000000625 cyclamic acid and its Na and Ca salt Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 239000001761 ethyl methyl cellulose Substances 0.000 description 1
- 235000010944 ethyl methyl cellulose Nutrition 0.000 description 1
- FSXVSUSRJXIJHB-UHFFFAOYSA-M ethyl prop-2-enoate;methyl 2-methylprop-2-enoate;trimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]azanium;chloride Chemical compound [Cl-].CCOC(=O)C=C.COC(=O)C(C)=C.CC(=C)C(=O)OCC[N+](C)(C)C FSXVSUSRJXIJHB-UHFFFAOYSA-M 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000008369 fruit flavor Substances 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 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
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 235000010449 maltitol Nutrition 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
- 229960001855 mannitol Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 235000019656 metallic taste Nutrition 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 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
- 230000007935 neutral effect Effects 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229960001462 sodium cyclamate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 235000019408 sucralose Nutrition 0.000 description 1
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229920003176 water-insoluble polymer Polymers 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/223—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of alpha-aminoacids
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- 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
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
-
- 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
- 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
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
- A61K9/5047—Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Emergency Medicine (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Tadı maskelenmiş rasekadotril ile diyare tedavisinde kullanılmak üzere yaş granülasyon yöntemi ile tadı maskelenmiş rasekadotril içeren tablet, dispers tablet (ağızda dağılan tablet), süspansiyon gibi farmasötik bileşimlerle ilgilidir.
Description
TARiFNAME
Teknik alan:
Mevcut bulus, tadi maskelenmis rasekadotril ile diyare tedavisinde kullanilmak üzere yas
granülasyon yöntemi kullanilarak tadi maskelenmis rasekadotril içeren farmasötik
bilesimlerle ilgilidir.
Onceki teknik:
Rasekadotril (Racecadotril) diyare tedavisinde kullanilan bir etkin maddedir (l). Ilk defa
US4513009 patentinde açiklanmistir. Rasekadotril ayni zamanda asetorfan (acetorphane)
ismiyle bilinir. Rasekadotril içeren farmasötik ürünler piyasada Hidrasec, Tiorfan, Tiorfix
Piyasada bulunan kapsül formu 100mg, tablet formu 175mg ve çocuklar için kullanilan
markalari ile bulunur.
sase formu 10mg veya 30mg Rasekadotril içerir.
EP pediatrik kullanimlarda tercih edilen Rasekadotril kuru toz
formülasyonunu kapsar. Formülasyonun özelligi uygun bir tasiyici ile hazirlanmis
Rasekadotril granülesinin kaplanmasi ve tatlandirici ile karistirilmasidir. Kaplama ajani
olarak akrilat veya metakrilat polimerleri, özellikle Eudragit NE 30D belirtilmistir. Prosese
göre önce bir miktar seker ile rasekadotril granülesi hazirlanir, granüle kaplama ajani ile
kaplanir; kaplanmis granüle kalan seker, aerosil ve tatlandirici ile karistirilir ve sase içine
EP Rasekadotril tablet formülasyonu, WO çocuklarda kullanim için
süspansiyon formülasyonu ile ilgilidir.
Bilindigi gibi çocuklarda ilaç kullaniminda kolaylik açisindan en fazla süspansiyon formu
tercih edilmektedir. Ancak rasekadotril hidrofobik bir madde oldugundan süspansiyon
formunda hazirlanmasinda zorluklar vardir. Keza kuru toz formülasyonlari gibi dozaj
formlarinda bazen doz uniformite sorunlari ile karsilasilmaktadir. Bu nedenle hem
çocuklara kolay verilebilecek, hem üretimi daha kolay olacak, hem de homojen doz
dagilimi saglayacak dispers tablet formu tercih edilmistir.
Dispers tabletler veya diger ismi ile agizda dagilan tabletler suda çabuk dagilan
tabletlerdir. Özelligi dagilma sürelerinin 1 dakikadan az, tercihen 40 saniye veya daha kisa
olmasidir. Agizda dagilabildiginden su ile yutulmasi gerekmez. Ayrica dispers tabletlerin
tadi ve sertligi kabul edilebilir olmalidir.
Bulusun açiklamasi:
Bulusa göre, tadi maskelenmis Rasekadotril içeren dispers tablet olup, özelligi
Rasekadotril etkin maddesinin herhangi bir eksipiyan ile karistirilmadan yas granülasyon
yöntemi kullanilarak etil akrilat - metil metakrilat kopolimeri ile kaplanarak tadinin
maskelenmis olmasi olup, etil akrilat - metil metakrilat polimer miktari Rasekadotril
miktarina göre agirlikça %1 - %10'dur.
Formülasyon yas granülasyon teknigi ile hazirlanmis ve dispers tablet (agizda dagilan
tablet) olarak basilmistir. Yas granülasyon islemi sirasinda Rasekadotril bilesigi herhangi
bir yardimci madde veya tasiyici ile karistirilmadan dogrudan yas granülasyona tabi
tutulmustur. Böylece Rasekadotril bilesiginin aci tadi maskelenmistir. Sadece Rasekadotril
bilesiginin tat maskeleyici bir materyal ile yas granülasyona tabi tutulmasi teknigin bilinen
durumunda yeni bir prosestir.
Yas granülasyon prosesi ile tat maskeleme için hidroksipropilmetil selüloz,
hidroksietilselL'iloz, hidroksimetilseli'iloz, hidroksipropilselüloz, hidroksietilmetil selüloz,
sodyum karboksimetilseli'iloz, etil selüloz, metil selüloz gibi selüloz polimerleri ile akrilik
asit polimerleri veya kopolimerleri kullanilabilir. Akrilat polimerleri olarak etil akrilat - metil
metakrilat kopolimeri, dimetil aminoetil metakrilat kopolimeri (Eudragit E 100, Eudragit E
12,5 ve Eudragit E PO) ile amonyum metakrilat kopolimeri (Eudragit RL ve Eudragit RS)
kullanilabilir. Yas granülasyon için suda disperse olabilen etil akrilat - metil metakrilat
kopolimeri seçilmistir. Kopolimer içeriginde etil akrilatin metil metakrilata orani yaklasik
2:1'dir. Etil akrilat ve metil metakrilat esasli nötral kopolimerin sulu dispersiyonu halinde
olan bu polimer piyasada Eudragit NE 30 D ticari adi ile bulunur. 8qu dispersiyonun kati
madde orani %30”dur. Bu polimer Avrupa Farmakopesinde %30'Iuk poliakrilat
dispersiyonu (Polyacrylat Dispersion 30 Percent) monografi, US/NF'de etil akrilat ve Metil
Metakrilat Kopolimer Dispersiyonu (Ethyl Acrylate and Methyl Methacrylate Copolymer
Dispersion) ismi ile yer almaktadir.
EP patentinde sase formunda kullanilan rasekadotrilin agirlikça %15
miktarinda etil akrilat-metil metakrilat kopolimeri kullanilmistir, ancak dagilabilir tablet
formülasyonunda, etil akrilat-metil metakrilat kopolimer orani, istenilen çözünme profili ve
tat maskelemesi elde etmek için rasekadotrilin agirlikça %1 - %10 araliginda
kullanilmistir.
Dispers tabletler Rasekadotril tabletler gibi 5 mg ila 175 mg arasinda Rasekadotril içerir.
Tercih edilen birim dozaj 30 mg'dir.
Yas granülasyona tabi tutularak tadi maskelenmis Rasekadotril, ara 'ürün olarak tablet,
dispers tablet, süspansiyon gibi farmasötik bilesimlerin hazirlanmasinda kullanilabilir.
Dispers tablet formülasyonu için yas granülasyon yöntemi ile tadi maskelenmis
Rasekadotril, asagida belirtilen yardimci maddeler ile karistirilarak tablet haline getirilir.
Seyreltici ve akiskanlik verici olarak mannitol, sorbitol, maltitol ve xylitol gibi polioller
kullanilabilir. Pearlitol ticari adi ile bilinen mannitol tercih edilmistir. Dispers tablette DC
mannitol %30-70 oraninda kullanilabilir. Tercihen yaklasik % 50 oraninda kullanilmistir.
Onceki tekniklerde Rasekadotril granülesi için seyreltici olarak seker kullanimi
bilinmektedir (EP1294372). Gelistirilen Rasekadotril dispers tablet yeni olarak mannitol
içermektedir.
Tabletlerde dagitici olarak kullanilan çesitli bilesikler mevcut olup, dagitici olarak süper
dagitici olarak bilinen Kollidon CL seçilmistir. Kollidon CL ticari adi ile bilinen çapraz bagli
povidon (çapraz bagli polivinilpirolidon), ayni zamanda krospovidon ve suda çözünmeyen
polivinilpirolidon olarak da bilinir. Dispers tablette povidon %5-25 oraninda kullanilmistir.
Tabletlerde ayrica baglayici, dagitici ve kaydirici özellikleri olan prejelatinize nisasta
kullanilmistir. Dispers tablette prejelatinize nisasta %5-30 oraninda kullanilmistir.
Tabletlerde kaydirici olarak çesitli stearat bilesikleri, stearik asit, hidrojene hint yagi gibi
bitkisel yaglar kullanilabilir. Dispers tabletlerde magnezyum stearatin bazik yapisindan
dolayi agizda biraktigi metalik tadi önlemek ve hasta uyuncunu artirabilmek amaciyla
kaydirici olarak sodyum stearil fumarat kullanilmistir.
Tatlandirici olarak sakkarin, sodyum siklamat, acesulfam potasyum, aspartam, sukraloz
gibi çesitli tatlandiricilar kullanilabilir. Tatlandirici sistemi olarak aspartam-asesulfam
potasyum karisimi seçilmistir. Dispers tablete uygun bir tad vermek için agirlikça yaklasik
miktarina orani agirlikça 522 oranindadir.
Aroma olarak ise muz, çilek, ahududu, seftali gibi meyve aromalari içinden çilek aromasi
seçilmistir.
Asagidaki örnekler bulusu açiklar, ancak kisitlamaz.
Rasekadotril 30 mg Dispers Tablet asagidaki birim formüle göre hazirlanmistir:
Maddeler (mg) (%)
Rasekadotril 30,0 12,50
Eudragit NE 30D 0,6 0,25
Aspartam 10,0 4,17
Kollidon CL 30,0 12,50
Mannitol 125,6 52,33
Ases'ülfam K 4,0 1,67
Prejelatinize nisasta 26,0 10,83
Çilek aromasi 9,0 3,75
Sodyum stearil fumarat 4,8 2,00
Toplam 240,0 100,00
Rasekadotril 0.8 mm elekten elenir ve üzerine saf su ile hazirlanmis Eudragit NE-30D
ilave edilerek yas granüle hazirlanir. Yas granüle elenip kurutulduktan sonra 'önce
aspartam, kollidon CL, mannitol, asesülfam K, prejelatinize nisasta ve çilek aromasi,
daha sonra sodyum stearil fumarat ile karistirilir ve tablet haline getirilir.
Rasekadotril 30 mg Dispers Tablet asagidaki birim formüle göre hazirlanmistir:
Maddeler (mg) (%)
Rasekadotril 30,0 12,50
Aspartam 10,0 4,17
Kollidon CL 30,0 12,50
Mannitol 123,8 51,58
Ases'ülfam K 4,0 1,67
Prejelatinize nisasta 26,0 10,83
Çilek aromasi 9,0 3,75
Sodyum stearil fumarat 4,8 2,00
Toplam 240,0 100,00
Rasekadotril 0.8 mm elekten elenir ve üzerine saf su ile hazirlanmis HPMC çözeltisi
ilave edilerek yas granüle hazirlanir. Yas granüle elenip kurutulduktan sonra önce
aspartam, kollidon CL, mannitol, ases'ülfam K, prejelatinize nisasta ve çilek aromasi,
daha sonra sodyum stearil fumarat ile karistirilir ve tablet haline getirilir.
Suda çözünen polimerin tat maskeleme etkinliginin suda çözünmeyen polimerden daha
az olmasi nedeni ile tad maskelemede kullanilan HPMC polimer miktari Eudragit NE
30Diye göre daha fazladir.
Claims (1)
- ISTEMLER Tadi maskelenmis Rasekadotril içeren dispers tablet olup, özelligi Rasekadotril etkin maddesinin herhangi bir eksipiyan ile karistirilmadan yas granülasyon yöntemi kullanilarak etil akrilat - metil metakrilat kopolimeri ile kaplanarak tadinin maskelenmis olmasi olup, etil akrilat - metil metakrilat polimer miktari Rasekadotril miktarina göre agirlikça %1 - %10'dur. Istem 1`e göre dispers tablet olup, tablet agirligina göre agirlikça %30-70 mannitol, %5- 25 krospovidon, % 5-30 prejelatinize nisasta ve %05-2 sodyum stearil fumarat içerir. Istem 2'e göre dispers tablet olup, tatlandirici olarak aspartam ve asesulfam potasyum Istem ?fe göre dispers tablet olup, aspartam miktarinin asesulfam potasyum miktarina Istem 1'e göre dispers tablet olup, tablet içerigi 5 - 175 mg Rasekadotril içerir. Istem 5'e göre dispers tablet olup, 30 mg Rasekadotril içerir.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR201215298 | 2012-12-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TR201801726T4 true TR201801726T4 (tr) | 2018-03-21 |
Family
ID=49876340
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TR2018/01726T TR201801726T4 (tr) | 2012-12-26 | 2013-12-17 | Rasekadotri̇l ve farmasöti̇k bi̇leşi̇mleri̇. |
Country Status (2)
| Country | Link |
|---|---|
| EP (1) | EP2749270B1 (tr) |
| TR (1) | TR201801726T4 (tr) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2013282413B2 (en) | 2012-06-28 | 2018-04-19 | Mcneil-Ppc, Inc. | Racecadotril lipid compositions |
| US9801819B2 (en) | 2012-06-28 | 2017-10-31 | Johnson & Johnson Consumer Inc. | Racecadotril compositions |
| MA40859A (fr) * | 2014-10-29 | 2017-09-05 | Johnson & Johnson Consumer Inc | Particules de cadotril |
| US20190274964A1 (en) * | 2016-08-23 | 2019-09-12 | Johnson & Johnson Consumer Inc. | New improved composition of racecadotril |
| WO2018163195A1 (en) | 2017-03-06 | 2018-09-13 | Athena Drug Delivery Solutions Pvt Ltd. | A pharmaceutical composition comprising racecadotril and process for preparing the same |
| CN109589310A (zh) * | 2017-10-01 | 2019-04-09 | 北京万全德众医药生物技术有限公司 | 消旋卡多曲干混悬剂及其制备方法 |
| EP4056171A1 (en) | 2021-03-12 | 2022-09-14 | Athena Pharmaceutiques SAS | Taste masked racecadotril tablet composition and process for preparation thereof |
| CN114469873B (zh) * | 2022-01-20 | 2023-01-31 | 首都医科大学附属北京儿童医院 | 一种含消旋卡多曲的药物制剂及其制备方法 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1635884A (zh) * | 2000-06-23 | 2005-07-06 | 生物计划公司 | 包含外消旋卡朵曲的干粉制剂 |
| FR2900823B1 (fr) * | 2006-05-15 | 2009-02-13 | Bioprojet Soc Civ Ile | Nouvelle forme d'administration du racecadotril. |
-
2013
- 2013-12-17 TR TR2018/01726T patent/TR201801726T4/tr unknown
- 2013-12-17 EP EP13005858.9A patent/EP2749270B1/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| EP2749270B1 (en) | 2018-01-17 |
| EP2749270A1 (en) | 2014-07-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TR201801726T4 (tr) | Rasekadotri̇l ve farmasöti̇k bi̇leşi̇mleri̇. | |
| CN102764242B (zh) | 含有pde 4抑制剂作为活性成分和聚乙烯吡咯烷酮作为赋形剂的口服剂型 | |
| Nyol et al. | Immediate drug release dosage form: a review | |
| WO2018108128A1 (zh) | 葡萄糖激酶激活剂的口服制剂及其制备方法 | |
| KR101528954B1 (ko) | 이미다페나신 함유 구강 내 속붕괴성 정제 | |
| JP2023063386A (ja) | シロドシンの苦味をマスキングした経口投与製剤 | |
| KR102241643B1 (ko) | 비정질 톨밥탄을 함유하는 경구 투여 현탁제 | |
| ZA200200344B (en) | Method for making granules with masked taste and instant release of the active particle. | |
| US11279682B2 (en) | Vortioxetine pyroglutamate | |
| WO2011110939A2 (en) | Pharmaceutical compositions of substituted benzhydrylpiperazines | |
| US20230240999A1 (en) | Novel fine particle coating (drug-containing hollow particle and method for manufacturing same) | |
| JPWO2016051782A1 (ja) | 苦味を有する薬剤の苦味をマスキングした経口投与製剤 | |
| WO2015142178A1 (en) | Bile acid composition with enhanced solubility | |
| EP2170310A2 (en) | Quick dissolve compositions of memantine hydrochloride | |
| WO2010081722A2 (en) | Orally disintegrating tablets for the treatment of pain | |
| US20110060008A1 (en) | Pharmaceutical composition containing acetylcholine esterase inhibitor and method for the preparation thereof | |
| CN110603035A (zh) | 具有改善的水溶解度及生物利用率的组合物 | |
| US11957792B2 (en) | Taste-masked pharmaceutical compositions containing diclofenac | |
| AU2016220638A1 (en) | An oral pharmaceutical formulation comprising sustained-release granules containing tamsulosin hydrochloride | |
| Patel et al. | Formulation design and optimization of tastemasked mouth-dissolving tablets of Tramadol hydrochloride | |
| ES2731598T3 (es) | Formulación pediátrica que comprende ácido biliar | |
| Alghabban et al. | Taste masking of prifinium bromide in orodispersible tablets | |
| CN117357481A (zh) | 一种口服掩味药物组合物的制备工艺 | |
| Chaudhari et al. | Formulation development and evaluation of orally disintegrating tablets of doxazosin mesylate | |
| US9498441B2 (en) | Nitazoxadine composition and process to prepare same |