TR202016210A2 - Pharmaceutical form containing acidic substance - Google Patents
Pharmaceutical form containing acidic substance Download PDFInfo
- Publication number
- TR202016210A2 TR202016210A2 TR2020/16210A TR202016210A TR202016210A2 TR 202016210 A2 TR202016210 A2 TR 202016210A2 TR 2020/16210 A TR2020/16210 A TR 2020/16210A TR 202016210 A TR202016210 A TR 202016210A TR 202016210 A2 TR202016210 A2 TR 202016210A2
- Authority
- TR
- Turkey
- Prior art keywords
- pharmaceutical form
- weight
- form according
- acid
- feature
- Prior art date
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- 239000000126 substance Substances 0.000 title claims abstract description 32
- 230000002378 acidificating effect Effects 0.000 title claims abstract description 30
- 239000011230 binding agent Substances 0.000 claims abstract description 13
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 117
- 239000008188 pellet Substances 0.000 claims description 62
- 235000015165 citric acid Nutrition 0.000 claims description 39
- 239000000203 mixture Substances 0.000 claims description 19
- 230000007935 neutral effect Effects 0.000 claims description 19
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 18
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 18
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 18
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 18
- 239000000725 suspension Substances 0.000 claims description 18
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 17
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 17
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 17
- 239000000454 talc Substances 0.000 claims description 16
- 229910052623 talc Inorganic materials 0.000 claims description 16
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 10
- 239000011248 coating agent Substances 0.000 claims description 9
- 238000000576 coating method Methods 0.000 claims description 9
- 235000019359 magnesium stearate Nutrition 0.000 claims description 5
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 4
- 108010010803 Gelatin Proteins 0.000 claims description 4
- DLRVVLDZNNYCBX-UHFFFAOYSA-N Polydextrose Polymers OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(O)O1 DLRVVLDZNNYCBX-UHFFFAOYSA-N 0.000 claims description 4
- 229920002125 Sokalan® Polymers 0.000 claims description 4
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 claims description 4
- 235000010443 alginic acid Nutrition 0.000 claims description 4
- 229920000615 alginic acid Polymers 0.000 claims description 4
- 229960001631 carbomer Drugs 0.000 claims description 4
- 229920000159 gelatin Polymers 0.000 claims description 4
- 239000008273 gelatin Substances 0.000 claims description 4
- 229940014259 gelatin Drugs 0.000 claims description 4
- 235000019322 gelatine Nutrition 0.000 claims description 4
- 235000011852 gelatine desserts Nutrition 0.000 claims description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 229930006000 Sucrose Natural products 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000002245 particle Substances 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 239000005720 sucrose Substances 0.000 claims description 3
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 2
- 229920002907 Guar gum Polymers 0.000 claims description 2
- 229920000881 Modified starch Polymers 0.000 claims description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 2
- 229920001100 Polydextrose Polymers 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 2
- 239000001361 adipic acid Substances 0.000 claims description 2
- 235000011037 adipic acid Nutrition 0.000 claims description 2
- 229940072056 alginate Drugs 0.000 claims description 2
- 239000000783 alginic acid Substances 0.000 claims description 2
- 229960001126 alginic acid Drugs 0.000 claims description 2
- 150000004781 alginic acids Chemical class 0.000 claims description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
- 230000000181 anti-adherent effect Effects 0.000 claims description 2
- 239000011668 ascorbic acid Substances 0.000 claims description 2
- 229960005070 ascorbic acid Drugs 0.000 claims description 2
- 235000010323 ascorbic acid Nutrition 0.000 claims description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 2
- 239000008116 calcium stearate Substances 0.000 claims description 2
- 235000013539 calcium stearate Nutrition 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 235000010418 carrageenan Nutrition 0.000 claims description 2
- 239000000679 carrageenan Substances 0.000 claims description 2
- 229920001525 carrageenan Polymers 0.000 claims description 2
- 229940113118 carrageenan Drugs 0.000 claims description 2
- 239000001530 fumaric acid Substances 0.000 claims description 2
- 235000011087 fumaric acid Nutrition 0.000 claims description 2
- 239000008103 glucose Substances 0.000 claims description 2
- 235000010417 guar gum Nutrition 0.000 claims description 2
- 239000000665 guar gum Substances 0.000 claims description 2
- 229960002154 guar gum Drugs 0.000 claims description 2
- 229920002674 hyaluronan Polymers 0.000 claims description 2
- 229960003160 hyaluronic acid Drugs 0.000 claims description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
- 239000011976 maleic acid Substances 0.000 claims description 2
- 239000001630 malic acid Substances 0.000 claims description 2
- 235000011090 malic acid Nutrition 0.000 claims description 2
- 229920001206 natural gum Polymers 0.000 claims description 2
- 229920001277 pectin Polymers 0.000 claims description 2
- 239000001814 pectin Substances 0.000 claims description 2
- 235000010987 pectin Nutrition 0.000 claims description 2
- 229960000292 pectin Drugs 0.000 claims description 2
- 229960000502 poloxamer Drugs 0.000 claims description 2
- 229920001983 poloxamer Polymers 0.000 claims description 2
- 229920002401 polyacrylamide Polymers 0.000 claims description 2
- 235000013856 polydextrose Nutrition 0.000 claims description 2
- 239000001259 polydextrose Substances 0.000 claims description 2
- 229940035035 polydextrose Drugs 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 229920000193 polymethacrylate Polymers 0.000 claims description 2
- 229920001282 polysaccharide Polymers 0.000 claims description 2
- 239000005017 polysaccharide Substances 0.000 claims description 2
- 150000004804 polysaccharides Chemical class 0.000 claims description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 2
- 235000010413 sodium alginate Nutrition 0.000 claims description 2
- 239000000661 sodium alginate Substances 0.000 claims description 2
- 229940005550 sodium alginate Drugs 0.000 claims description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 2
- 229960004793 sucrose Drugs 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- 229920001285 xanthan gum Polymers 0.000 claims description 2
- 235000010493 xanthan gum Nutrition 0.000 claims description 2
- 239000000230 xanthan gum Substances 0.000 claims description 2
- 229940082509 xanthan gum Drugs 0.000 claims description 2
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 claims description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 229920000642 polymer Polymers 0.000 claims 1
- 235000012222 talc Nutrition 0.000 claims 1
- 239000002535 acidifier Substances 0.000 abstract description 5
- 239000002775 capsule Substances 0.000 abstract description 5
- 238000009472 formulation Methods 0.000 description 9
- 238000005507 spraying Methods 0.000 description 9
- 238000013270 controlled release Methods 0.000 description 7
- 229940079593 drug Drugs 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 5
- 238000004090 dissolution Methods 0.000 description 5
- 239000001069 triethyl citrate Substances 0.000 description 5
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 5
- 235000013769 triethyl citrate Nutrition 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 4
- 125000005395 methacrylic acid group Chemical group 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 3
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 3
- 229920003151 Eudragit® RL polymer Polymers 0.000 description 3
- 229920003152 Eudragit® RS polymer Polymers 0.000 description 3
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 3
- 239000007963 capsule composition Substances 0.000 description 3
- 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 3
- 229960001021 lactose monohydrate Drugs 0.000 description 3
- 125000005397 methacrylic acid ester group Chemical group 0.000 description 3
- 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 3
- HWMFFWCDLWDYGX-UHFFFAOYSA-N n-(4-aminophenyl)furan-2-carboxamide Chemical compound C1=CC(N)=CC=C1NC(=O)C1=CC=CO1 HWMFFWCDLWDYGX-UHFFFAOYSA-N 0.000 description 3
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 3
- XTUSEBKMEQERQV-UHFFFAOYSA-N propan-2-ol;hydrate Chemical compound O.CC(C)O XTUSEBKMEQERQV-UHFFFAOYSA-N 0.000 description 3
- 229960001187 propiverine hydrochloride Drugs 0.000 description 3
- 229920003137 Eudragit® S polymer Polymers 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000036765 blood level Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- QPCVHQBVMYCJOM-UHFFFAOYSA-N Propiverine Chemical group C=1C=CC=CC=1C(C=1C=CC=CC=1)(OCCC)C(=O)OC1CCN(C)CC1 QPCVHQBVMYCJOM-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000020971 citrus fruits Nutrition 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- YBSJFWOBGCMAKL-UHFFFAOYSA-N dabigatran Chemical compound N=1C2=CC(C(=O)N(CCC(O)=O)C=3N=CC=CC=3)=CC=C2N(C)C=1CNC1=CC=C(C(N)=N)C=C1 YBSJFWOBGCMAKL-UHFFFAOYSA-N 0.000 description 1
- 229960003850 dabigatran Drugs 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 238000009474 hot melt extrusion Methods 0.000 description 1
- 239000012943 hotmelt Substances 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000007909 melt granulation Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 150000002734 metacrylic acid derivatives Chemical class 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 229960003510 propiverine Drugs 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 238000005563 spheronization Methods 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 125000000185 sucrose group Chemical group 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- 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
Abstract
Mevcut buluş; bir çekirdek, pKa değeri 6.65'ten az olan asidik bir madde ve en az bir bağlayıcı içeren bir farmasötik form ile ilgili olup, burada çekirdek, pKa değeri 6.65'ten az olan asidik bir maddeyle ve en az bir bağlayıcıyla kaplıdır. Farmasötik form, asitleştirme ajanı olarak tablet veya kapsül formlarında kullanılabilir.The present invention; relates to a pharmaceutical form comprising a core, an acidic substance with a pKa of less than 6.65 and at least one binder, wherein the core is covered with an acidic substance with a pKa of less than 6.65 and at least one binder. The pharmaceutical form can be used as an acidifying agent in tablet or capsule forms.
Description
TARFNAME ASIDIK MADDE IÇEREN FARMASÖTIK FORM Teknik Alan Mevcut bulus; bir çekirdek, pKa degeri 6.65'ten az olan asidik bir madde ve en az bir baglayici içeren bir farmasötik form ile ilgili olup, burada çekirdek, pKa degeri 6.65'ten az olan asidik bir maddeyle ve en az bir baglayiciyla kaplidir. Farmasötik form, asitlestirme ajani olarak tablet veya kapsül formlarinda kullanilabilir. DESCRIPTION PHARMACEUTICAL FORM CONTAINING ACIDIC SUBSTANCE Technical Field Present invention; a nucleus, an acidic substance with a pKa value of less than 6.65, and at least one Pertaining to a pharmaceutical form containing a linker, wherein the core has a pKa value of less than 6.65 It is covered with an acidic substance and at least one binder. Pharmaceutical form, acidifying agent It can be used in tablet or capsule forms.
Bulusun Bilinen Durumu Farmasötik maddelerin kontrollü salim formülasyonlari, farmasötik ve tip alanlarinda son derece büyük bir pazardir. Terapötik kan seviyelerinin uzun süreler boyunca sürdürülmesinde etkili olan kontrollü salim formülasyonlarinin optimal tedaviyle sonuçlandigi konunun uzmanlari tarafindan bilinmektedir. Iyilestirilmis hasta rahatligi ve uyumu için dozlam sikligini azaltmakla kalmaz, ayni zamanda büyük ölçüde sabit kan seviyelerini koruduklari ve günde üç ila dört kez uygulanan geleneksel hizli salim formülasyonlariyla iliskili dalgalanmalari önlediklerinden dolayi yan etkilerin siddetini ve sikligini da azaltirlar. Çogu kontrollü salim sisteminden ilaç salim hizi ve boyutu, pH'a bagli çözünürlüge sahip ilaçlarda çözünme ortaminin pH'indan etkilenir. Özellikle organik asitler, farmasötik dozaj formlarinin iç ortaminin pH'sini degistirerek ilacin çözünürlügünü kontrol etmek için kullanilabilir. Known Status of the Invention Controlled release formulations of pharmaceutical substances are the latest developments in pharmaceutical and medical fields. It is a huge market. Therapeutic blood levels are maintained for long periods of time Controlled release formulations that are effective in maintaining It is known by experts in the field. For improved patient comfort and compliance not only reduces dosing frequency but also maintains substantially constant blood levels. with traditional immediate-release formulations that protect and are administered three to four times daily Since they prevent associated fluctuations, they also reduce the severity and frequency of side effects. The rate and extent of drug release from most controlled release systems have pH-dependent resolution. Dissolution of drugs is affected by the pH of the environment. In particular, organic acids change the pH of the internal environment of pharmaceutical dosage forms and Can be used to check resolution.
Bu bulusta, pKa degeri 6.65'ten düsük olan asidik maddenin formülasyonda dogrudan kullanimi için alternatif bir yol bulunmustur. pKa degeri 6.65'ten düsük olan asidik maddeye sahip pelletler hazirlanmistir. In this invention, the acidic substance with a pKa value of less than 6.65 is directly used in the formulation. An alternative way has been found for its use. acidic substance with pKa value less than 6.65 pellets were prepared.
Günümüzde pelletler, çok patriküllü oral ilaç vermede baskin rol oynamaktadir. Pelletler, farmasötik uygulamalar için tipik olarak 500 ile 1500 mm arasinda degisen, dar boyut dagilimina sahip küresel, serbest akisli granüller olarak tanimlanir. Bu pelletlerin, kontrollü salim gibi tek birimli dozaj formlarina göre pek çok avantaji bulunmaktadir. Pelletler, yüksek ilaç konsantrasyonu nedeniyle olusan yan etki riskini azaltabilir, ilaç emilimini en üst düzeye çikarabilir, küresel sekil, dar boyut dagilimi ile iyi bir akis özelligi sergiler. Today, pellets play the dominant role in multiparticulate oral drug delivery. pellets, Narrow size, typically between 500 and 1500 mm for pharmaceutical applications They are defined as spherical, free-flowing granules with a uniform distribution. These pellets are controlled It has many advantages over single unit dosage forms such as release. Pellets, high It can reduce the risk of side effects due to drug concentration and maximize drug absorption. Removable, spherical shape, narrow size distribution and good flow properties.
Bu bulusta, farmasötik form, pKa degeri 6.65 düsük olan asidik maddeye sahip pellet elde edilmistir. Bu, kontrollü salimli formülasyonlar için bir asitlestirme ajani olarak bir tablet veya kapsül formunda kullanilabilir. In this invention, the pharmaceutical form is obtained by obtaining a pellet with an acidic substance with a pKa value of 6.65. has been done. It can be used as a tablet or as an acidifying agent for controlled-release formulations. It can be used in capsule form.
Böylece, ortamin pH'ini ayarlayan ve iyi çözünme profili saglamaya yardimci olacak sekilde formülasyonun stabilitesini artiran, farmasötik form gelistirilmistir. Thus, it adjusts the pH of the medium and helps ensure a good dissolution profile. A pharmaceutical form has been developed that increases the stability of the formulation.
Bulusun Ayrintili Açiklamasi Bulusun temel amaci, bir farmasötik form elde etmektir. Bu farmasötik form bir formülasyonda kullanildiginda formülasyonun istenen çözünme profilini ve stabilitesini saglamasina yardimci olur. Detailed Description of the Invention The main purpose of the invention is to obtain a pharmaceutical form. This pharmaceutical form is a When used in the formulation, it provides the desired dissolution profile and stability of the formulation. It helps to ensure.
Bulusun bir diger amaci, kontrollü salimli formülasyonlar için etkin ve diger eksipiyanlar ile etkilesmeyen bir farmasötik form saglamaktir. kompakt kütleler anlamina gelir. olan asidik maddeyle ve en az bir eksipiyanla kaplanmis bir çekirdek anlamina gelir. Ayrica bulustaki farmasötik form anlamina gelir. Another purpose of the invention is to provide controlled release formulations with active and other excipients. to provide a non-interfering pharmaceutical form. It means compact masses. means a core coated with an acidic substance and at least one excipient. Moreover means the pharmaceutical form of the invention.
Bulusun bir uygulamasina göre bir farmasötik form bir çekirdekten, pKa degeri 6.65'ten düsük olan bir asidik maddeden ve en az bir baglayicidan olusur, burada çekirdek pKa degeri 6.65'ten düsük olan bir asidik maddeyle ve en az bir baglayiciyla kaplanmistir. According to one embodiment of the invention, a pharmaceutical form consists of a nucleus with a pKa value of less than 6.65. It consists of an acidic substance with a low pKa and at least one linker, where the core coated with an acidic substance having a value less than 6.65 and at least one binder.
Farmasötik form tablet veya kapsül formülasyonunda kullanildiginda, form düsük pH'ini ve böylece yeterince yüksek ilaç çözünürlügünü koruyabilir. Pelletlerin içinde pH düsük tutuldugunda ilacin kontrollü salimi saglanabilir. When used in pharmaceutical form tablet or capsule formulation, the form exhibits low pH and thus it can maintain high enough drug solubility. pH is low in pellets controlled release of the drug can be achieved.
Bulusun bir uygulamasina göre, farmasötik form, pKa degeri 6.65 düsük olan asidik maddeye sahip pellet tablet veya kapsül formlarinda asitlestirme ajani olarak kullanilabilir. According to an embodiment of the invention, the pharmaceutical form is acidic with a pKa value of less than 6.65. It can be used as an acidifying agent in pellet tablet or capsule forms.
Bulusun bir uygulamasina göre, çekirdek nötr mikrokristal yapida selüloz veya seker pelletidir. According to an embodiment of the invention, the core is cellulose or sugar in a neutral microcrystalline structure. pellet.
Bulusun bir uygulamasina göre seker pelleti sükroz veya nisastadir. According to one embodiment of the invention, the sugar pellet is sucrose or starch.
Bulusun bir uygulamasina göre pKa degeri 6.65'ten düsük olan bir asidik madde, sitrik asit, tartarik asit, malik asit, maleik asit, suksinik asit, askorbik asit, fumarik asit, adipik asit veya bunlarin farmasötik olarak kabul edilebilir tuzlari veya bunlarin bir karisimi olabilir. According to an embodiment of the invention, an acidic substance with a pKa value of less than 6.65, citric acid, tartaric acid, malic acid, maleic acid, succinic acid, ascorbic acid, fumaric acid, adipic acid or may be their pharmaceutically acceptable salts or a mixture thereof.
Sitrik asit kimyasal formülü Cngoy olan zayif bir organik asittir. Turunçgillerde dogal olarak bulunur. Biyokimyada, tüm aerobik organizmalarin metabolizmasinda gerçeklesen sitrik asit döngüsünde bir ara maddedir. Sitrik asit, çesitli farmasötik ve diger bilesimler için yaygin olarak kullanilmaktadir. Yaygin olarak asitlestirici, tatlandirici ve selatlama maddesi olarak kullanilir. Citric acid is a weak organic acid with the chemical formula Cngoy. Naturally found in citrus fruits is available. In biochemistry, citric acid occurs in the metabolism of all aerobic organisms. It is an intermediate in the cycle. Citric acid is widely used in various pharmaceutical and other compounds. It is used as. Commonly used as acidifier, sweetener and chelating agent is used.
Bulusun bir uygulamasina göre, pKa degeri 6.65'ten düsük bir asidik madde sitrik asittir. According to one embodiment of the invention, an acidic substance with a pKa value of less than 6.65 is citric acid.
Bulusun bir uygulamasina göre, tercihen çekirdek nötr mikrokristalin selüloz pelletidir ve nötr mikrokristalin selüloz pelletinin partikül boyutu 0,3 mm ile 0,7 mm arasindadir. Nötr mikrokristalin selüloz, kabul edilebilir gevreklik ve sicakliga karsi yüksek dirence sahip olmasiyla farmasötik form için uygun bir çekirdektir. According to one embodiment of the invention, preferably the core is a neutral microcrystalline cellulose pellet and The particle size of microcrystalline cellulose pellet is between 0.3 mm and 0.7 mm. Neutral microcrystalline cellulose has acceptable friability and high resistance to temperature It is a suitable core for pharmaceutical form.
Bulusun bir uygulamasina göre, nötr mikrokristalin selüloz pelletlerinin miktari farmasötik formda agirlikça %100 ile %400 arasindadir. According to one embodiment of the invention, the amount of neutral microcrystalline cellulose pellets is pharmaceutically acceptable. In its form, it is between 100% and 400% by weight.
Bulusun bir uygulamasina göre, nötr mikrokristalin selüloz pelletlerinin miktari farmasötik Bulusun bir somut örnegine göre, sitrik asit miktari farmasötik formda agirlikça %500 ile Bulusun bir uygulamasina göre, sitrik asit miktari farmasötik formda agirlikça %550 ile Bulusun bir uygulamasina göre, çekirdek aktif madde içermez. According to one embodiment of the invention, the amount of neutral microcrystalline cellulose pellets is pharmaceutically acceptable. According to an embodiment of the invention, the amount of citric acid in pharmaceutical form is 500% by weight. According to one embodiment of the invention, the amount of citric acid in pharmaceutical form is between 550% by weight. According to one embodiment of the invention, the core does not contain active ingredient.
Uygun baglayici, polivinilpirolidon, sodyum karboksimetil selüloz, hidroksipropil metilselüloz, polietilen glikol, polivinil alkol, önceden jelatinize edilmis nisasta, glikoz, dogal zamklar, sukroz, sodyum alginat, jelatin, karagenan, guar zamk, karbomer, polimetakrilatlar, metakrilatlardan olusan gruptan seçilir. jelatin, aljinat, aljinik asit, ksantan zamki, hiyaluronik asit, pektin, polisakkaritler, karbomer, poloksamer, poliakrilamid, polioksietilen-alkil eter, polidekstroz, polietilen oksit veya bunlarin karisimlari arasindan seçilir. Suitable binder is polyvinylpyrrolidone, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, polyethylene glycol, polyvinyl alcohol, pregelatinized starch, glucose, natural gums, sucrose, sodium alginate, gelatin, carrageenan, guar gum, carbomer, polymethacrylates, It is selected from the group consisting of methacrylates. gelatin, alginate, alginic acid, xanthan gum, hyaluronic acid, pectin, polysaccharides, carbomer, poloxamer, polyacrylamide, polyoxyethylene-alkyl ether, polydextrose, polyethylene oxide, or mixtures thereof.
Mevcut bulusun bir uygulamasina göre, baglayici polivinilpirolidondur. According to one embodiment of the present invention, the binder is polyvinylpyrrolidone.
Mevcut bulusun bir uygulamasina göre, baglayici miktari farmasötik formda agirlikça %0.5 ile Bulusun bir uygulamasina göre, baglayici miktari farmasötik formda agirlikça %10 ile %60 veya %10 ile %40 arasindadir. According to one embodiment of the present invention, the amount of binder can be between 0.5% by weight in pharmaceutical form. According to an embodiment of the invention, the amount of binder is 10% to 60% by weight in pharmaceutical form. or between 10% and 40%.
Bulusun bir uygulamasina göre, farmasötik form ayrica en azindan magnezyum stearat, kalsiyum stearat, talk veya bunlarin karisimlari arasindan seçilen antiadeziv madde içerir. According to one embodiment of the invention, the pharmaceutical form further comprises at least magnesium stearate, It contains an antiadhesive agent selected from calcium stearate, talc or mixtures thereof.
Mevcut bulusun bir uygulamasina göre, çekirdek sitrik asit, polivinilpirolidon ve talk ile kaplanmistir. According to one embodiment of the present invention, the core is mixed with citric acid, polyvinylpyrrolidone and talc. is covered.
Mevcut bulusun bir uygulamasina göre, sitrik asit pelletlerinin partikül boyutu 0.8 mm ile 1.4 mm arasindadir. According to one embodiment of the present invention, the particle size of citric acid pellets is between 0.8 mm and 1.4 mm. mm.
Bulusun bir uygulamasina göre, pKa degeri 6.65 düsük olan asidik maddeye sahip pellet, sicak eriyik granülasyon, sicak eriyik ekstrüzyon, akiskan yatak granülasyonu, ekstrüzyon/sferonizasyon, püskürtmeyle kurutma ve çözücü buharlastirma gibi teknikte iyi bilinen standart teknikler ve üretim prosesleri kullanilarak hazirlanabilir. According to an embodiment of the invention, a pellet with an acidic substance with a pKa value of less than 6.65, hot melt granulation, hot melt extrusion, fluidized bed granulation, Good at techniques such as extrusion/spheronization, spray drying and solvent evaporation It can be prepared using known standard techniques and production processes.
Bulusun bir uygulamasina göre, pKa degeri 6.65 düsük olan asidik maddeye sahip pellet, akiskan yatakli granülatörle püskürtme yoluyla hazirlanir. Bu sayede istenilen homojen ve stabilite formu elde edilir. According to an embodiment of the invention, a pellet with an acidic substance with a pKa value of less than 6.65, It is prepared by spraying with a fluidized bed granulator. In this way, the desired homogeneous and stability form is obtained.
Bulusun bir uygulamasina göre, pKa degeri 6.65 düsük olan asidik maddeye sahip pellet sunlari içerir; - Agirlikça %100 - %400 nötr mikrokristalin selüloz pellet, - Agirlikça %0.5 - %100 polivinilpirolidon, - Agirlikça %500 - %850 pKa degeri 6.65'ten düsük olan asidik madde, - Agirlikça %1.0 - %70 talk, toplam pKa degeri 6.65 düsük olan asidik maddeye sahip pellete göre. According to an embodiment of the invention, a pellet with an acidic substance with a pKa value of less than 6.65 It includes; - 100% - 400% neutral microcrystalline cellulose pellet by weight, - 0.5% - 100% polyvinylpyrrolidone by weight, - 500% - 850% by weight acidic substance with a pKa value less than 6.65, - 1.0% - 70% talc by weight, has acidic substance with a low total pKa value of 6.65 by pellet.
Mevcut bulusun bir uygulamasina göre sitrik asit pelletleri sunlari içerir; - Agirlikça %100 - %400 nötr mikrokristalin selüloz pellet, - Agirlikça %0.5 - %100 polivinilpirolidon, - Agirlikça %500 - %850 sitrik asit, - Agirlikça %1.0 - %70 talk, toplam sitrik asit pelletlerine göre. According to one embodiment of the present invention, citric acid pellets contain; - 100% - 400% neutral microcrystalline cellulose pellet by weight, - 0.5% - 100% polyvinylpyrrolidone by weight, - 500% - 850% citric acid by weight, - 1.0% - 70% talc by weight, based on total citric acid pellets.
Bulusun bir uygulamasina göre, pKa degeri 6.65 düsük olan asidik maddeye sahip pellet hazirlanmasina yönelik proses asagidaki adimlari içerir: - Saf suda pKa degeri 6.65'ten düsük olan asidik madde, polivinilpirolidon ve talk Ilave edilerek süspansiyon elde edilmesi, - Süspansiyonun akiskan yatakli kurutucuda kaplama için nötr mikrokristalin selüloz pellete püskürtülmesi, - pKa degeri 6.65 pelletten düsük olan yuvarlak asidik madde elde edilmesi. According to an embodiment of the invention, a pellet with an acidic substance with a pKa value of less than 6.65 The process for its preparation includes the following steps: - Acidic substance, polyvinylpyrrolidone and talc with pKa value less than 6.65 in pure water Addition obtaining suspension by - The suspension is converted into neutral microcrystalline cellulose pellets for coating in a fluidized bed dryer. spraying, - Obtaining a round acidic substance with a pKa value lower than 6.65 pellet.
Bulusun bir uygulamasina göre, sitrik asit pelletlerinin hazirlanmasina yönelik proses, asagidaki adimlari içerir: - Saf suya sitrik asit, polivinilpirolidon ve talk ilave edilerek süspansiyon elde edilmesi, - Süspansiyonun akiskan yatakli kurutucuda kaplama için nötr mikrokristalin selüloz pellete püskürtülmesi, - Yuvarlak sitrik asit pelletlerin elde edilmesi. According to one embodiment of the invention, the process for preparing citric acid pellets is It includes the following steps: - Obtaining a suspension by adding citric acid, polyvinylpyrrolidone and talc to pure water, - Neutral microcrystalline cellulose for coating the suspension in a fluidized bed dryer spraying the pellet, - Obtaining round citric acid pellets.
Bulusun bir uygulamasina göre, söz konusu farmasötik form, zayif asidik veya bazik pH degerlerinde çözünme profilini artirmak için sitrik asit içerir. Sitrik asit pelletleri, 17 saatlik çözünme süresi boyunca mikroçevre pH'inin modülasyonundan kaynaklanan, bir aktif maddenin kontrollü bir sekilde salinmasina (pH degerine bagli çözünürlügü) yol açar. According to one embodiment of the invention, said pharmaceutical form has a slightly acidic or basic pH. Contains citric acid to increase its dissolution profile. Citric acid pellets, 17 hour resulting from modulation of microenvironment pH during the dissolution period. It causes a controlled release of the substance (solubility dependent on pH value).
Bulusun bir uygulamasina göre bir aktif madde, propiverin veya farmasötik olarak kabul edilebilir bir tuzu veya dabigatran veya bunun farmasötik olarak kabul edilebilir bir tuzu olabilir. Örnek 1: Sitrik asit pelletleri Içindekiler Agirlikça % Nötr mikrokristalin selüloz pellet 10.0 - 40.0 Polivinilpirolidon 0.5 - 10.0 Sitrik asit 50.0 - 85.0 TOPLAM 100 Örnek 2: Sitrik asit pelletleri Içindekiler Agirlikça % Nötr mikrokristalin selüloz pellet 22.40 Polivinilpirolidon 2.8 Sitrik asit 70.0 TOPLAM 100 Örnek 1 veya 2 için proses Saf suya sitrik asit, polivinilpirolidon ve talk ilave edilerek süspansiyon elde edilmesi, - Süspansiyonun akiskan yatakli kurutucuda kaplama için nötr mikrokristalin selüloz pellete püskürtülmesi, - Yuvarlak sitrik asit pelletleri elde edilmesi. Örnek 3: Yukarida açiklanan kapsül formülasyonundaki sitrik asit pelletlerin kullanimi Içindekiler Agirlikça % Sitrik asit pelletleri 45.0 _ 60.0 Propiverin hidroklorür 8.0 _ 200 Sitrik asit 1_0 _ 5_0 Laktoz monohidrat 1_0 _ 10_0 Trietilsitrat 0_5 _ 5_0 Magnezyum stearat (101 _ 1_0 Etil akrilat veya metil metakrilat veya düsük metakrilik asit ester içerigi (Eudragit RS veya 1_0 _ 50 Eudragit RL) TOPLAM 100 Örnek 4: Yukarida açiklanan kapsül formülasyonunda sitrik asit pelletlerin kullanimi Içindekiler Agirlikça % Sitrik asit pelletleri 55 Propiverin hidroklorür 147 Polivinilpirolidon 3.8 Sitrik asit 20 Laktoz monohidrat 4_0 Trietilsitrat 1.1 Magnezyum stearat 0.1 Etil akrilat veya metil metakrilat veya düsük metakrilik asit ester içerigi (Eudragit RS veya 2.8 Eudragit RL) TOPLAM 100 Örnek 3 veya 4 için proses Ilk adim; a) Izopropil alkol-su karisimina sitrik asit, polivinilpirrolidon, Iaktoz monohidrat ve talk eklenmesi ve ardindan süspansiyon elde edilmesi, b) Süspansiyonun akiskan yatakli kurutucuda kaplama için sitrik asit pelletlerine püskürtülmesi ve yuvarlak pellet 1 elde edilmesi, Ikinci adim; c) Izopropil alkol-su karisimina POIi(metakrilik asit-ko-metilmetakrilat) 1:2 (Eudragit S 100), poli(metakrilik asit-ko-metil metakrilat) , trietil sitrat ve talk eklenmesi ve süspansiyon elde edilmesi, d) Süspansiyonun akiskan yatakli kurutucuda kaplama için yuvarlak pellet 1'e püskürtülmesi ve yuvarlak pellet 2 elde edilmesi, Üçüncü adim; e) Izopropil alkol-su karisimina propiverin hidroklorür, sitrik asit, polivinilpirrolidon, talk ve magnezyum stearat eklenmesi ve ardindan süspansiyon elde edilmesi, f) Süspansiyonun akiskan yatakli kurutucuda kaplama için yuvarlak pellet 2'e püskürtülmesi ve yuvarlak pellet 3 elde edilmesi, Dördüncü adim; g) Izopropil alkol-su-aseton karisimina etil akrilat veya metil metakrilat veya düsük metakrilik asit ester içerigi (Eudragit RS veya Eudragit RL), poli(metakrilik asit-ko- metilmetakrilat) , trietilsitrat ve talk eklenmesi ve ardindan süspansiyon elde edilmesi; h) Süspansiyonun akiskan yatakli kurutuouda kaplama için yuvarlak pellet 3'e püskürtülmesi ve yuvarlak pellet 4 elde edilmesi, Besinci adim; i) Izopropil alkol-su karisimina poli(metakrilik asit-ko-metilmetakrilat) 1:2 (Eudragit S 100), trietilsitrat ve talk eklenmesi ve ardindan süspansiyon elde edilmesi, j) Süspansiyonun akiskan yatakli kurutucuda kaplama için yuvarlak pellet 4'e püskürtülmesi ve yuvarlak pellet 5 elde edilmesi, k) Yuvarlak pelletin 5'in kürlenmesi, Altinci adim; m) Yuvarlak pelletlerin kapsüle doldurulmasi. According to one embodiment of the invention, an active ingredient is propiverine or pharmaceutically acceptable dabigatran or a pharmaceutically acceptable salt thereof. it could be. Example 1: Citric acid pellets Ingredients % by weight Neutral microcrystalline cellulose pellet 10.0 - 40.0 Polyvinylpyrrolidone 0.5 - 10.0 Citric acid 50.0 - 85.0 TOTAL 100 Example 2: Citric acid pellets Ingredients % by weight Neutral microcrystalline cellulose pellet 22.40 Polyvinylpyrrolidone 2.8 Citric acid 70.0 TOTAL 100 Process for example 1 or 2 Obtaining a suspension by adding citric acid, polyvinylpyrrolidone and talc to pure water, - Neutral microcrystalline cellulose for coating the suspension in a fluidized bed dryer spraying the pellet, - Obtaining round citric acid pellets. Example 3: Use of citric acid pellets in the capsule formulation described above Ingredients % by weight Citric acid pellets 45.0 _ 60.0 Propiverine hydrochloride 8.0 _ 200 Citric acid 1_0 _ 5_0 Lactose monohydrate 1_0 _ 10_0 Triethylcitrate 0_5 _ 5_0 Magnesium stearate (101 _ 1_0 Ethyl acrylate or methyl methacrylate or low methacrylic acid ester content (Eudragit RS or 1_0 _50 Eudragit RL) TOTAL 100 Example 4: Use of citric acid pellets in the capsule formulation described above Ingredients % by weight Citric acid pellets 55 Propiverine hydrochloride 147 Polyvinylpyrrolidone 3.8 Citric acid 20 Lactose monohydrate 4_0 Triethylcitrate 1.1 Magnesium stearate 0.1 Ethyl acrylate or methyl methacrylate or low methacrylic acid ester content (Eudragit RS or 2.8 Eudragit RL) TOTAL 100 Process for example 3 or 4 First step; a) Add citric acid, polyvinylpyrrolidone, lactose monohydrate and talc to the isopropyl alcohol-water mixture. adding and then obtaining a suspension, b) The suspension is converted into citric acid pellets for coating in a fluidized bed dryer. spraying and obtaining round pellet 1, Second step; c) Add POIi(methacrylic acid-co-methylmethacrylate) 1:2 (Eudragit S) to isopropyl alcohol-water mixture. 100), poly(methacrylic acid-co-methyl methacrylate), triethyl citrate and talc adding and obtaining suspension, d) Dissolve the suspension into round pellet 1 for coating in the fluidized bed dryer. spraying and obtaining round pellet 2, Third step; e) Propiverine hydrochloride, citric acid, polyvinylpyrrolidone, talc and adding magnesium stearate and then obtaining a suspension, f) Turn the suspension into round pellets 2 for coating in the fluidized bed dryer. spraying and obtaining round pellet 3, Fourth step; g) Add ethyl acrylate or methyl methacrylate or low concentration to the isopropyl alcohol-water-acetone mixture. methacrylic acid ester content (Eudragit RS or Eudragit RL), poly(methacrylic acid-co- methylmethacrylate), triethylcitrate and talc followed by obtaining suspension; h) Round pellets for coating in fluidized bed drying of the suspension are reduced to 3. spraying and obtaining round pellet 4, Fifth step; i) Add poly(methacrylic acid-co-methylmethacrylate) 1:2 (Eudragit S) to isopropyl alcohol-water mixture. 100), adding triethylcitrate and talc and then obtaining a suspension, j) Dissolve the suspension into round pellets 4 for coating in the fluidized bed dryer. spraying and obtaining round pellet 5, k) Curing of the round pellet 5, Sixth step; m) Filling of round pellets into the capsule.
Claims (15)
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP20889151.5A EP4061369A4 (en) | 2019-11-19 | 2020-10-27 | A pharmaceutical form comprising acidic substance |
| PCT/TR2020/051001 WO2021101483A1 (en) | 2019-11-19 | 2020-10-27 | A pharmaceutical form comprising acidic substance |
| CA3162409A CA3162409A1 (en) | 2019-11-19 | 2020-10-27 | A pharmaceutical form comprising acidic substance |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2019/18013A TR201918013A2 (en) | 2019-11-19 | 2019-11-19 | A pellet composition comprising propiverine or a pharmaceutically acceptable salt thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TR202016210A2 true TR202016210A2 (en) | 2021-06-21 |
Family
ID=75980701
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TR2019/18013A TR201918013A2 (en) | 2019-11-19 | 2019-11-19 | A pellet composition comprising propiverine or a pharmaceutically acceptable salt thereof |
| TR2020/16210A TR202016210A2 (en) | 2019-11-19 | 2020-10-12 | Pharmaceutical form containing acidic substance |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TR2019/18013A TR201918013A2 (en) | 2019-11-19 | 2019-11-19 | A pellet composition comprising propiverine or a pharmaceutically acceptable salt thereof |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP4061370A4 (en) |
| CA (1) | CA3162408A1 (en) |
| TR (2) | TR201918013A2 (en) |
| WO (1) | WO2021101481A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023080856A1 (en) * | 2021-11-03 | 2023-05-11 | Santa Farma Ilac Sanayii A.S. | Enteric coated pharmaceutical composition of propiverine hydrochloride |
| WO2023128906A1 (en) * | 2021-12-30 | 2023-07-06 | Santa Farma Ilac Sanayii A.S. | Release of propiverine compositions in gastric conditions |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10149674A1 (en) * | 2001-10-09 | 2003-04-24 | Apogepha Arzneimittel Gmbh | Orally administered composition for sustained release of propiverine, useful for treatment of hypertonic bladder disorders, especially by once-daily administration |
| ITMI20061024A1 (en) * | 2006-05-25 | 2007-11-26 | Eurand Pharmaceuticals Ltd | PELLETS BASED ON LIPOIC ACID |
| TWI519322B (en) * | 2008-04-15 | 2016-02-01 | 愛戴爾製藥股份有限公司 | Compositions comprising weakly basic drugs and controlled-release dosage forms |
| CN102579404A (en) | 2012-01-17 | 2012-07-18 | 广州科的信医药技术有限公司 | Sustained-release capsule containing propiverine hydrochloride and preparation method of sustained-release capsule |
-
2019
- 2019-11-19 TR TR2019/18013A patent/TR201918013A2/en unknown
-
2020
- 2020-10-12 TR TR2020/16210A patent/TR202016210A2/en unknown
- 2020-10-27 EP EP20889321.4A patent/EP4061370A4/en active Pending
- 2020-10-27 WO PCT/TR2020/050998 patent/WO2021101481A1/en unknown
- 2020-10-27 CA CA3162408A patent/CA3162408A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| WO2021101481A1 (en) | 2021-05-27 |
| EP4061370A1 (en) | 2022-09-28 |
| TR201918013A2 (en) | 2021-06-21 |
| CA3162408A1 (en) | 2021-05-27 |
| EP4061370A4 (en) | 2023-08-02 |
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