CA3162409A1 - A pharmaceutical form comprising acidic substance - Google Patents
A pharmaceutical form comprising acidic substanceInfo
- Publication number
- CA3162409A1 CA3162409A1 CA3162409A CA3162409A CA3162409A1 CA 3162409 A1 CA3162409 A1 CA 3162409A1 CA 3162409 A CA3162409 A CA 3162409A CA 3162409 A CA3162409 A CA 3162409A CA 3162409 A1 CA3162409 A1 CA 3162409A1
- Authority
- CA
- Canada
- Prior art keywords
- pharmaceutical form
- weight
- form according
- acid
- citric acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 230000002378 acidificating effect Effects 0.000 title claims abstract description 30
- 239000000126 substance Substances 0.000 title claims abstract description 30
- 239000011230 binding agent Substances 0.000 claims abstract description 15
- 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 66
- 239000000454 talc Substances 0.000 claims description 21
- 229910052623 talc Inorganic materials 0.000 claims description 21
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 20
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 20
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 20
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 20
- 230000007935 neutral effect Effects 0.000 claims description 20
- 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
- 239000000203 mixture Substances 0.000 claims description 16
- 239000012530 fluid Substances 0.000 claims description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 10
- 238000005507 spraying Methods 0.000 claims description 10
- 235000015165 citric acid Nutrition 0.000 claims description 9
- 239000011248 coating agent Substances 0.000 claims description 9
- 238000000576 coating method Methods 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 6
- 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
- 239000013543 active substance Substances 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
- 150000003839 salts Chemical class 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
- 239000002245 particle Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 239000005720 sucrose Substances 0.000 claims description 3
- 235000012222 talc Nutrition 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
- 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
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 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
- 239000000853 adhesive Substances 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
- 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
- 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
- 229920000642 polymer 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
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims 1
- 239000001630 malic acid Substances 0.000 claims 1
- 235000011090 malic acid Nutrition 0.000 claims 1
- 239000002775 capsule Substances 0.000 abstract description 6
- 239000002535 acidifier Substances 0.000 abstract description 5
- 238000009472 formulation Methods 0.000 description 9
- 125000005395 methacrylic acid group Chemical group 0.000 description 8
- 238000013270 controlled release Methods 0.000 description 7
- 229940079593 drug Drugs 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 238000002156 mixing Methods 0.000 description 6
- 229920003141 Eudragit® S 100 Polymers 0.000 description 5
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 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
- 238000004090 dissolution Methods 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- XTUSEBKMEQERQV-UHFFFAOYSA-N propan-2-ol;hydrate Chemical compound O.CC(C)O XTUSEBKMEQERQV-UHFFFAOYSA-N 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
- 229920003139 Eudragit® L 100 Polymers 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
- 239000008187 granular material Substances 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
- 229960001187 propiverine hydrochloride Drugs 0.000 description 3
- 230000036765 blood level Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000009826 distribution Methods 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 compound 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
- 239000002253 acid Substances 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 235000020971 citrus fruits Nutrition 0.000 description 1
- 238000013267 controlled drug release Methods 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
- 239000012738 dissolution medium Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 238000011049 filling Methods 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
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000007909 melt granulation Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000008177 pharmaceutical agent Substances 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
- 239000003826 tablet Substances 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000004102 tricarboxylic acid cycle Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
-
- 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
- A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
- A61K9/1676—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface having a drug-free core with discrete complete coating layer containing drug
-
- 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
Abstract
The present invention relates to a pharmaceutical form comprises a core, an acidic substance having a pKa value of less than 6.65 and at least one binder wherein the core is coated with an acidic substance having a pKa value of less than 6.65 and at least one binder. The pharmaceutical form may use in a form of tablet or capsule as an acidifying agent.
Description
A PHARMACEUTICAL FORM COMPRISING ACIDIC SUBSTANCE
Field of the Invention The present invention relates to a pharmaceutical form comprises a core, an acidic substance having a pKa value of less than 6.65 and at least one binder wherein the core is coated with an acidic substance having a pKa value of less than 6.65 and at least one binder. The pharmaceutical form may use in a form of tablet or capsule as an acidifying agent.
Background of the Invention Controlled release formulations of pharmaceutical agents are an extremely large market in the pharmaceutical and medical fields. It is well known to those skilled in the art that controlled release formulations which are effective in maintaining therapeutic blood levels over extended periods to time result in optimal therapy. They not only reduce the frequency of dosing for enhanced patient convenience and compliance, but they also reduce the severity and frequency of side effects, as they maintain substantially constant blood levels and avoid fluctuations associated with conventional immediate release formulations administered three to four times a day. The rate and extent of drug release from most controlled release systems are influenced by the pH of the dissolution medium for drugs with pH-dependent solubility.
.. Especially, organic acids can be used to control the solubility of drug by changing the pH of internal environment of the pharmaceutical dosage forms.
In this invention, an alternative way of using an acidic substance having a pKa value of less than 6.65 directly in the formulation has been found. An acidic substance having a pKa value of less than 6.65 pellets were prepared.
.. Nowadays, pellets are playing a dominating role in the world of multiparticulate oral drug delivery. Pellets are defined as spherical, free-flowing granules with a narrow size distribution, typically varying between 500 and 1500 mm for pharmaceutical applications.
These pellets have many advantages over single-unit dosage forms like controlled release.
Pellets can reduce the risk of side effect due to high drug concentration, maximise drug absorption, spherical shape exhibits a good flow property with narrow size distribution.
In this invention, the pharmaceutical form, the acidic substance having a pKa value of less than 6.65 pellet, was obtained. This may use in a form of tablet or capsule as an acidifying agent for controlled release formulations.
Thus, a pharmaceutical form has been developed that adjusts the pH of the medium and increases the stability of the formulation, helping to provide a good dissolution profile.
Detailed Description of the Invention The main objective of the invention is to provide a pharmaceutical form. When this pharmaceutical form is used in a formulation, it helps the formulation to provide the desired dissolution profile and provide the desired stability.
Another object of the present invention is to provide a pharmaceutical form for controlled release formulations that is effective and does not interact with other excipients.
The term "core" will refer to a compact mass having a definite geometric shape such as tablets, granules, pellets, capsules.
The term 'acidic substance having a pKa value of less than 6.65 pellet' will refer to a coated core with acidic substance having a pKa value of less than 6.65 and at least one excipient.
Also, it refers as pharmaceutical form in the present invention.
According to one embodiment of the present invention, a pharmaceutical form comprises a core, an acidic substance having a pKa value of less than 6.65 and at least one binder wherein the core is coated with an acidic substance having a pKa value of less than 6.65 and at least one binder. When the pharmaceutical form is used in the tablet or capsule formulation, the form is able to maintain a low pH and thus a sufficiently high drug solubility.
By maintaining a low pH inside the pellets, a controlled drug release can be achieved.
According to one embodiment of the present invention, the pharmaceutical form, the acidic substance having a pKa value of less than 6.65 pellets, may use in a form of tablet or capsule as an acidifying agent.
According to one embodiment of the present invention, the core is neutral microcrystalline cellulose pellet or sugar pellet.
According to one embodiment of the present invention, the sugar pellet is sucrose or starch.
According to one embodiment of the present invention, an acidic substance having a pKa value of less than 6.65 is selected from the group comprising citric acid, tartaric acid, malic
Field of the Invention The present invention relates to a pharmaceutical form comprises a core, an acidic substance having a pKa value of less than 6.65 and at least one binder wherein the core is coated with an acidic substance having a pKa value of less than 6.65 and at least one binder. The pharmaceutical form may use in a form of tablet or capsule as an acidifying agent.
Background of the Invention Controlled release formulations of pharmaceutical agents are an extremely large market in the pharmaceutical and medical fields. It is well known to those skilled in the art that controlled release formulations which are effective in maintaining therapeutic blood levels over extended periods to time result in optimal therapy. They not only reduce the frequency of dosing for enhanced patient convenience and compliance, but they also reduce the severity and frequency of side effects, as they maintain substantially constant blood levels and avoid fluctuations associated with conventional immediate release formulations administered three to four times a day. The rate and extent of drug release from most controlled release systems are influenced by the pH of the dissolution medium for drugs with pH-dependent solubility.
.. Especially, organic acids can be used to control the solubility of drug by changing the pH of internal environment of the pharmaceutical dosage forms.
In this invention, an alternative way of using an acidic substance having a pKa value of less than 6.65 directly in the formulation has been found. An acidic substance having a pKa value of less than 6.65 pellets were prepared.
.. Nowadays, pellets are playing a dominating role in the world of multiparticulate oral drug delivery. Pellets are defined as spherical, free-flowing granules with a narrow size distribution, typically varying between 500 and 1500 mm for pharmaceutical applications.
These pellets have many advantages over single-unit dosage forms like controlled release.
Pellets can reduce the risk of side effect due to high drug concentration, maximise drug absorption, spherical shape exhibits a good flow property with narrow size distribution.
In this invention, the pharmaceutical form, the acidic substance having a pKa value of less than 6.65 pellet, was obtained. This may use in a form of tablet or capsule as an acidifying agent for controlled release formulations.
Thus, a pharmaceutical form has been developed that adjusts the pH of the medium and increases the stability of the formulation, helping to provide a good dissolution profile.
Detailed Description of the Invention The main objective of the invention is to provide a pharmaceutical form. When this pharmaceutical form is used in a formulation, it helps the formulation to provide the desired dissolution profile and provide the desired stability.
Another object of the present invention is to provide a pharmaceutical form for controlled release formulations that is effective and does not interact with other excipients.
The term "core" will refer to a compact mass having a definite geometric shape such as tablets, granules, pellets, capsules.
The term 'acidic substance having a pKa value of less than 6.65 pellet' will refer to a coated core with acidic substance having a pKa value of less than 6.65 and at least one excipient.
Also, it refers as pharmaceutical form in the present invention.
According to one embodiment of the present invention, a pharmaceutical form comprises a core, an acidic substance having a pKa value of less than 6.65 and at least one binder wherein the core is coated with an acidic substance having a pKa value of less than 6.65 and at least one binder. When the pharmaceutical form is used in the tablet or capsule formulation, the form is able to maintain a low pH and thus a sufficiently high drug solubility.
By maintaining a low pH inside the pellets, a controlled drug release can be achieved.
According to one embodiment of the present invention, the pharmaceutical form, the acidic substance having a pKa value of less than 6.65 pellets, may use in a form of tablet or capsule as an acidifying agent.
According to one embodiment of the present invention, the core is neutral microcrystalline cellulose pellet or sugar pellet.
According to one embodiment of the present invention, the sugar pellet is sucrose or starch.
According to one embodiment of the present invention, an acidic substance having a pKa value of less than 6.65 is selected from the group comprising citric acid, tartaric acid, malic
2
3 acid, maleic acid, succinic acid, ascorbic acid, fumaric acid, adipic acid or pharmaceutically acceptable salts thereof or a mixture of thereof.
Citric acid is a weak organic acid that has the chemical formula C6H807. It occurs naturally in citrus fruits. In biochemistry, it is an intermediate in the citric acid cycle, which occurs in the metabolism of all aerobic organisms. Citric acid is used extensively for various compositions, pharmaceutical and otherwise. It is used widely as an acidifier, as a flavoring and a chelating agent.
According to one embodiment of the present invention, acidic substance having a pKa value of less than 6.65 is citric acid.
According to one embodiment of the present invention, preferably, the core is neutral microcrystalline cellulose pellet and the particle size of neutral microcrystalline cellulose pellet is between 0.3 mm and 0.7 mm. The neutral microcrystalline cellulose is a suitable core for the pharmaceutical form for having acceptable friability and high resistance to temperature.
According to one embodiment of the present invention, the amount of neutral microcrystalline cellulose pellets is between 10.0% and 40.0% by weight in the pharmaceutical form.
According to one embodiment of the present invention, the amount of neutral microcrystalline cellulose pellets is between 15.0% and 37.0% or between 20.0% and 35.0% by weight in the pharmaceutical form.
According to one embodiment of the present invention, the amount of citric acid is between 50.0% and 85.0% by weight in the pharmaceutical form.
According to one embodiment of the present invention, the amount of citric acid is between 55.0% and 80.0% or between 65.0% and 75.0% by weight in the pharmaceutical form.
According to one embodiment of the present invention, the core is free of active agent.
Suitable binder is selected from the group comprising polyvinylpyrrolidone, sodium carboxymethyl cellulose, hydroxypropyl methylcellu lose, polyethylene glycol, polyvinyl alcohol, pregelatinized starch, glucose, natural gums, sucrose, sodium alginate, gelatin, carrageenan, guar gum, carbomer, polymethacrylates, methacrylate polymers, gelatin, alginate, alginic acid, xanthan gum, hyaluronic acid, pectin, polysaccharides, carbomer, poloxamer, polyacrylamide, polyoxyethylene-alkyl ether, polydextrose, polyethylene oxide or mixtures thereof.
According to one embodiment of the present invention, binder is polyviylpyrrolidone.
According to one embodiment of the present invention, the amount of the binder is between 0.5% and 10.0% by weight in the pharmaceutical form.
According to one embodiment of the present invention, the amount of the binder is between 1.0% and 6.0% or between 1.0% and 4.0% by weight in the pharmaceutical form.
According to one embodiment of the present invention, the pharmaceutical form further comprises at least anti-adhesive agent which is selected from the group comprising magnesium stearate, calcium stearate, talc or mixtures thereof.
According to one embodiment of the present invention, the core is coated with citric acid, polyvinylpyrrolidone and talc.
According to one embodiment of the present invention, the particle size of citric acid pellets is between 0.8 mm and 1.4 mm.
According to one embodiment of the present invention, the acidic substance having a pKa value of less than 6.65 pellets may be prepared, using standard techniques and manufacturing processes well known in the art, such as hot melt granulation, hot melt extrusion, fluidized bed granulation, extrusion/spheronization, spray drying and solvent evaporation.
According to one embodiment of the present invention, the acidic substance having a pKa value of less than 6.65 pellets are prepared with spraying by fluid bed granulator. In this way, it provides to obtain the desired homogeneous and stability form.
According to one embodiment of the present invention, the acidic substance having a pKa value of less than 6.65 pellets comprises;
- 10.0% ¨ 40.0% by weight of neutral microcrystalline cellulose pellet, - 0.5%¨ 10.0% by weight of polyvinylpyrrolidone, - 50.0% ¨ 85.0% by weight of acidic substance having a pKa value of less than 6.65, - 1.0% ¨ 7.0% by weight of talc of the total the acidic substance having a pKa value of less than 6.65 pellets.
According to one embodiment of the present invention, the citric acid pellets comprises;
- 10.0% ¨ 40.0% by weight of neutral microcrystalline cellulose pellet, - 0.5%¨ 10.0% by weight of polyvinylpyrrolidone, - 50.0% ¨ 85.0% by weight of citric acid,
Citric acid is a weak organic acid that has the chemical formula C6H807. It occurs naturally in citrus fruits. In biochemistry, it is an intermediate in the citric acid cycle, which occurs in the metabolism of all aerobic organisms. Citric acid is used extensively for various compositions, pharmaceutical and otherwise. It is used widely as an acidifier, as a flavoring and a chelating agent.
According to one embodiment of the present invention, acidic substance having a pKa value of less than 6.65 is citric acid.
According to one embodiment of the present invention, preferably, the core is neutral microcrystalline cellulose pellet and the particle size of neutral microcrystalline cellulose pellet is between 0.3 mm and 0.7 mm. The neutral microcrystalline cellulose is a suitable core for the pharmaceutical form for having acceptable friability and high resistance to temperature.
According to one embodiment of the present invention, the amount of neutral microcrystalline cellulose pellets is between 10.0% and 40.0% by weight in the pharmaceutical form.
According to one embodiment of the present invention, the amount of neutral microcrystalline cellulose pellets is between 15.0% and 37.0% or between 20.0% and 35.0% by weight in the pharmaceutical form.
According to one embodiment of the present invention, the amount of citric acid is between 50.0% and 85.0% by weight in the pharmaceutical form.
According to one embodiment of the present invention, the amount of citric acid is between 55.0% and 80.0% or between 65.0% and 75.0% by weight in the pharmaceutical form.
According to one embodiment of the present invention, the core is free of active agent.
Suitable binder is selected from the group comprising polyvinylpyrrolidone, sodium carboxymethyl cellulose, hydroxypropyl methylcellu lose, polyethylene glycol, polyvinyl alcohol, pregelatinized starch, glucose, natural gums, sucrose, sodium alginate, gelatin, carrageenan, guar gum, carbomer, polymethacrylates, methacrylate polymers, gelatin, alginate, alginic acid, xanthan gum, hyaluronic acid, pectin, polysaccharides, carbomer, poloxamer, polyacrylamide, polyoxyethylene-alkyl ether, polydextrose, polyethylene oxide or mixtures thereof.
According to one embodiment of the present invention, binder is polyviylpyrrolidone.
According to one embodiment of the present invention, the amount of the binder is between 0.5% and 10.0% by weight in the pharmaceutical form.
According to one embodiment of the present invention, the amount of the binder is between 1.0% and 6.0% or between 1.0% and 4.0% by weight in the pharmaceutical form.
According to one embodiment of the present invention, the pharmaceutical form further comprises at least anti-adhesive agent which is selected from the group comprising magnesium stearate, calcium stearate, talc or mixtures thereof.
According to one embodiment of the present invention, the core is coated with citric acid, polyvinylpyrrolidone and talc.
According to one embodiment of the present invention, the particle size of citric acid pellets is between 0.8 mm and 1.4 mm.
According to one embodiment of the present invention, the acidic substance having a pKa value of less than 6.65 pellets may be prepared, using standard techniques and manufacturing processes well known in the art, such as hot melt granulation, hot melt extrusion, fluidized bed granulation, extrusion/spheronization, spray drying and solvent evaporation.
According to one embodiment of the present invention, the acidic substance having a pKa value of less than 6.65 pellets are prepared with spraying by fluid bed granulator. In this way, it provides to obtain the desired homogeneous and stability form.
According to one embodiment of the present invention, the acidic substance having a pKa value of less than 6.65 pellets comprises;
- 10.0% ¨ 40.0% by weight of neutral microcrystalline cellulose pellet, - 0.5%¨ 10.0% by weight of polyvinylpyrrolidone, - 50.0% ¨ 85.0% by weight of acidic substance having a pKa value of less than 6.65, - 1.0% ¨ 7.0% by weight of talc of the total the acidic substance having a pKa value of less than 6.65 pellets.
According to one embodiment of the present invention, the citric acid pellets comprises;
- 10.0% ¨ 40.0% by weight of neutral microcrystalline cellulose pellet, - 0.5%¨ 10.0% by weight of polyvinylpyrrolidone, - 50.0% ¨ 85.0% by weight of citric acid,
4 - 1.0% - 7.0% by weight of talc of the total the citric acid pellets.
According to one embodiment of the present invention, the process for the preparation of acidic substance having a pKa value of less than 6.65 pellets comprises steps of:
- Adding acidic substance having a pKa value of less than 6.65, polyvinylpyrrolidone and talc in pure water and obtained a suspension, - Spraying the suspension to neutral microcrystalline cellulose pellet for coating at fluid bed dryer, - Obtained round acidic substance having a pKa value of less than 6.65 pellets.
According to one embodiment of the present invention, the process for the preparation of citric acid pellets comprises steps of:
- Adding citric acid, polyvinylpyrrolidone and talc in pure water and obtained a suspension, - Spraying the suspension to neutral microcrystalline cellulose pellet for coating at fluid bed dryer, - Obtained round citric acid pellets.
According to one embodiment of the present invention, the said pharmaceutical form comprises citric acid to increasing the dissolution profile in weak acidic or basic pH values.
The citric acid pellets led to a controlled release of an active agent (solubility of its dependent on the pH value), resulting from modulation of the microenvironmental pH
throughout the dissolution period of 17 hours.
According to one embodiment of the present invention, an active agent may be propiverine or a pharmaceutically acceptable salt thereof or dabigatran or a pharmaceutically acceptable salt thereof.
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 Talc 1.0 ¨ 7.0
According to one embodiment of the present invention, the process for the preparation of acidic substance having a pKa value of less than 6.65 pellets comprises steps of:
- Adding acidic substance having a pKa value of less than 6.65, polyvinylpyrrolidone and talc in pure water and obtained a suspension, - Spraying the suspension to neutral microcrystalline cellulose pellet for coating at fluid bed dryer, - Obtained round acidic substance having a pKa value of less than 6.65 pellets.
According to one embodiment of the present invention, the process for the preparation of citric acid pellets comprises steps of:
- Adding citric acid, polyvinylpyrrolidone and talc in pure water and obtained a suspension, - Spraying the suspension to neutral microcrystalline cellulose pellet for coating at fluid bed dryer, - Obtained round citric acid pellets.
According to one embodiment of the present invention, the said pharmaceutical form comprises citric acid to increasing the dissolution profile in weak acidic or basic pH values.
The citric acid pellets led to a controlled release of an active agent (solubility of its dependent on the pH value), resulting from modulation of the microenvironmental pH
throughout the dissolution period of 17 hours.
According to one embodiment of the present invention, an active agent may be propiverine or a pharmaceutically acceptable salt thereof or dabigatran or a pharmaceutically acceptable salt thereof.
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 Talc 1.0 ¨ 7.0
5 Example 2: Citric acid pellets Ingredients % by weight Neutral microcrystalline cellulose pellet 22.40 Polyvinylpyrrolidone 2.8 Citric acid 70.0 Talc 4.8 Process for example 1 or 2;
- Adding citric acid, polyvinylpyrrolidone and talc in pure water and obtained a suspension, - Spraying the suspension to neutral microcrystalline cellulose pellet for coating at fluid bed dryer, - Obtained round citric acid pellets.
Example 3: Using the above described citric acid pellets in a capsule formulation Ingredients % by weight Citric acid pellets 45.0 ¨ 60.0 Propiverine hydrochloride 8.0 ¨ 20.0 Polyvinylpyrrolidone 1.0 ¨ 7.0 Citric acid 1.0 ¨ 5.0 Lactose monohydrate 1.0 ¨ 10.0 Talc 5.0 ¨ 15.0 Poly(methacrylic acid-co-methylmethacrylate) 1:2 (Eudragit S 100) 1.0 ¨ 7.0 Poly(methacrylic acid-co-methylmethacrylate) 1:1 (Eudragit L 100) 0.5 ¨ 5.0 Triethylcitrate 0.5 ¨ 5.0 Magnesium stearate 0.01 ¨ 1.0 Ethyl acrylate or methyl methacrylate or a low content of methacrylic acid ester (Eudragit RS 1.0 ¨ 5.0 or Eudragit RL)
- Adding citric acid, polyvinylpyrrolidone and talc in pure water and obtained a suspension, - Spraying the suspension to neutral microcrystalline cellulose pellet for coating at fluid bed dryer, - Obtained round citric acid pellets.
Example 3: Using the above described citric acid pellets in a capsule formulation Ingredients % by weight Citric acid pellets 45.0 ¨ 60.0 Propiverine hydrochloride 8.0 ¨ 20.0 Polyvinylpyrrolidone 1.0 ¨ 7.0 Citric acid 1.0 ¨ 5.0 Lactose monohydrate 1.0 ¨ 10.0 Talc 5.0 ¨ 15.0 Poly(methacrylic acid-co-methylmethacrylate) 1:2 (Eudragit S 100) 1.0 ¨ 7.0 Poly(methacrylic acid-co-methylmethacrylate) 1:1 (Eudragit L 100) 0.5 ¨ 5.0 Triethylcitrate 0.5 ¨ 5.0 Magnesium stearate 0.01 ¨ 1.0 Ethyl acrylate or methyl methacrylate or a low content of methacrylic acid ester (Eudragit RS 1.0 ¨ 5.0 or Eudragit RL)
6 Example 4: Using the above described citric acid pellets in a capsule formulation Ingredients % by weight Citric acid pellets 55 Propiverine hydrochloride 14.7 Polyvinylpyrrolidone 3.8 Citric acid 2.0 Lactose monohydrate 4.0 Talc 10.0 Poly(methacrylic acid-co-methylmethacrylate) 1:2 (Eudragit S 100) 5.3 Poly(methacrylic acid-co-methylmethacrylate) 1.2 1:1 (Eudragit L 100) Triethylcitrate 1.1 Magnesium stearate 0.1 Ethyl acrylate or methyl methacrylate or a low content of methacrylic acid ester (Eudragit RS 2.8 or Eudragit RL) Process for example 3 or 4;
First step;
a) Adding citric acid, polyvinylpyrrolidone, lactose monohydrate and talc in a mixing isopropyl alcohol-water and then, obtained a suspension, b) Spraying the suspension to citric acid pellets for coating at fluid bed dryer and obtained rounded pellet 1, Second step;
c) Adding poly(methacrylic acid-co-methylmethacrylate) 1:2 (Eudragit S 100), poly (methacrylic acid-co-methyl methacrylate) 1:1 (Eudragit L 100), triethylcitrate and talc in a mixing isopropyl alcohol-water and then, obtained a suspension, d) Spraying the suspension to rounded pellet 1 for coating at fluid bed dryer and obtained rounded pellet 2, Third step;
e) Adding propiverine hydrochloride, citric acid, polyvinylpyrrolidone, talc and magnesium stearate in a mixing isopropyl alcohol-water and then, obtained a suspension,
First step;
a) Adding citric acid, polyvinylpyrrolidone, lactose monohydrate and talc in a mixing isopropyl alcohol-water and then, obtained a suspension, b) Spraying the suspension to citric acid pellets for coating at fluid bed dryer and obtained rounded pellet 1, Second step;
c) Adding poly(methacrylic acid-co-methylmethacrylate) 1:2 (Eudragit S 100), poly (methacrylic acid-co-methyl methacrylate) 1:1 (Eudragit L 100), triethylcitrate and talc in a mixing isopropyl alcohol-water and then, obtained a suspension, d) Spraying the suspension to rounded pellet 1 for coating at fluid bed dryer and obtained rounded pellet 2, Third step;
e) Adding propiverine hydrochloride, citric acid, polyvinylpyrrolidone, talc and magnesium stearate in a mixing isopropyl alcohol-water and then, obtained a suspension,
7 f) Spraying the suspension to rounded pellet 2 for coating at fluid bed dryer and obtained rounded pellet 3, Fourth step;
g) Adding ethyl acrylate or methyl methacrylate or a low content of methacrylic acid ester (Eudragit RS or Eudragit RL), poly(methacrylic acid-co-methylmethacrylate) 1:2 (Eudragit S 100), triethylcitrate and talc in a mixing isopropyl alcohol-water-acetone and then, obtained a suspension, h) Spraying the suspension to granule 3 for coating at fluid bed dryer and obtained rounded pellet 4, Fifth step;
i) Adding poly(methacrylic acid-co-methylmethacrylate) 1:2 (Eudragit S 100), triethylcitrate and talc in a mixing isopropyl alcohol-water and then, obtained a suspension, j) Spraying the suspension to rounded pellet 4 for coating at fluid bed dryer and obtained rounded pellet 5, k) Curing the rounded pellet 5, Sixth step;
I) Mixing the dried rounded pellet 5 and talc, m) Filling the rounded pellets into capsule.
g) Adding ethyl acrylate or methyl methacrylate or a low content of methacrylic acid ester (Eudragit RS or Eudragit RL), poly(methacrylic acid-co-methylmethacrylate) 1:2 (Eudragit S 100), triethylcitrate and talc in a mixing isopropyl alcohol-water-acetone and then, obtained a suspension, h) Spraying the suspension to granule 3 for coating at fluid bed dryer and obtained rounded pellet 4, Fifth step;
i) Adding poly(methacrylic acid-co-methylmethacrylate) 1:2 (Eudragit S 100), triethylcitrate and talc in a mixing isopropyl alcohol-water and then, obtained a suspension, j) Spraying the suspension to rounded pellet 4 for coating at fluid bed dryer and obtained rounded pellet 5, k) Curing the rounded pellet 5, Sixth step;
I) Mixing the dried rounded pellet 5 and talc, m) Filling the rounded pellets into capsule.
8
Claims (15)
1. A pharmaceutical form comprising a core, an acidic substance having a pKa value of less than 6.65 and at least one binder wherein the core is coated with citric acid and at least one binder.
2. The pharmaceutical form according to claim 1, wherein the core is neutral microcrystalline cellulose pellet or sugar pellet.
3. The pharmaceutical form according to claim 2, wherein the core is neutral microcrystalline cellulose pellet and the particle size of neutral microcrystalline cellulose pellet is between 0.3 mm and 0.7 mm.
4. The pharmaceutical form according to claim 3, wherein the amount of neutral microcrystalline cellulose pellets is between 10.0% and 40.0% by weight in the pharmaceutical form.
5. The pharmaceutical form according to claim 1, wherein the acidic substance having a pKa value of less than 6.65 is selected from the group comprising citric acid, tartaric acid, malic acid, maleic acid, succinic acid, ascorbic acid, fumaric acid, adipic acid or pharmaceutically acceptable salts thereof or a mixture of thereof.
6. The pharmaceutical form according to claim 5, wherein the acidic substance having a pKa value of less than 6.65 is citric acid.
7. The pharmaceutical form according to claim 6, wherein the amount of citric acid is between 50.0% and 85.0% by weight in the pharmaceutical form.
8. The pharmaceutical form according to claim 1, wherein the core is free of active agent.
9. The pharmaceutical form according to claim 1, wherein binder is selected from the group comprising polyvinylpyrrolidone, sodium carboxymethyl cellulose, polyethylene glycol, hydroxypropyl methylcellulose, polyvinyl alcohol, pregelatinized starch, glucose, natural gums, sucrose, sodium alginate, gelatin, carrageenan, guar gum, carbomer, polymethacrylates, methacrylate polymers, gelatin, alginate, alginic acid, xanthan gum, hyaluronic acid, pectin, polysaccharides, carbomer, poloxamer, polyacrylamide, polyoxyethylene-alkyl ether, polydextrose, polyethylene oxide or mixtures thereof.
10. The pharmaceutical form according to claim 9, wherein binder is polyviylpyrrolidone.
11. The pharmaceutical form according to claim 9, wherein the amount of the binder is between 0.5% and 10.0% by weight in the pharmaceutical form.
12. The pharmaceutical form according to claim 1, further comprising at least anti-adhesive agent which is selected from the group comprising magnesium stearate, calcium stearate, talc or mixtures thereof.
13. The pharmaceutical form according to claim 1, comprising;
- 10.0% ¨ 40.0% by weight of neutral microcrystalline cellulose pellet, - 0.5%¨ 10.0% by weight of polyvinylpyrrolidone, - 50.0% ¨ 85.0% by weight of acidic substance having a pKa value of less than 6.65, - 1.0% ¨ 7.0% by weight of talc of the total the acidic substance having a pKa value of less than 6.65 pellets.
- 10.0% ¨ 40.0% by weight of neutral microcrystalline cellulose pellet, - 0.5%¨ 10.0% by weight of polyvinylpyrrolidone, - 50.0% ¨ 85.0% by weight of acidic substance having a pKa value of less than 6.65, - 1.0% ¨ 7.0% by weight of talc of the total the acidic substance having a pKa value of less than 6.65 pellets.
14. The pharmaceutical form according to claim 6, comprising;
- 10.0% ¨ 40.0% by weight of neutral microcrystalline cellulose pellet, - 0.5%¨ 10.0% by weight of polyvinylpyrrolidone, - 50.0% ¨ 85.0% by weight of citric acid, - 1.0% ¨ 7.0% by weight of talc of total the citric acid pellets.
- 10.0% ¨ 40.0% by weight of neutral microcrystalline cellulose pellet, - 0.5%¨ 10.0% by weight of polyvinylpyrrolidone, - 50.0% ¨ 85.0% by weight of citric acid, - 1.0% ¨ 7.0% by weight of talc of total the citric acid pellets.
15. A process for the preparation of a pharmaceutical form according to claim 14, wherein the process further comprising steps of:
- Adding citric acid, polyvinylpyrrolidone and talc in pure water and obtained a suspension, - Spraying the suspension to neutral microcrystalline cellulose pellet for coating at fluid bed dryer, - Obtained round citric acid pellets.
- Adding citric acid, polyvinylpyrrolidone and talc in pure water and obtained a suspension, - Spraying the suspension to neutral microcrystalline cellulose pellet for coating at fluid bed dryer, - Obtained round citric acid pellets.
Applications Claiming Priority (5)
| 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 |
| TR2019/18013 | 2019-11-19 | ||
| TR2020/16210 | 2020-10-12 | ||
| TR2020/16210A TR202016210A2 (en) | 2019-11-19 | 2020-10-12 | Pharmaceutical form containing acidic substance |
| PCT/TR2020/051001 WO2021101483A1 (en) | 2019-11-19 | 2020-10-27 | A pharmaceutical form comprising acidic substance |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3162409A1 true CA3162409A1 (en) | 2021-05-27 |
Family
ID=75980705
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3162409A Pending CA3162409A1 (en) | 2019-11-19 | 2020-10-27 | A pharmaceutical form comprising acidic substance |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP4061369A4 (en) |
| CA (1) | CA3162409A1 (en) |
| WO (1) | WO2021101483A1 (en) |
Family Cites Families (6)
| 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 |
| SI2588090T1 (en) * | 2010-07-01 | 2017-06-30 | Krka, D.D., Novo Mesto | Pharmaceutical oral dosage forms comprising dabigatran etexilate and its pharmaceutically acceptable salts |
| 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 |
| CN103417544B (en) * | 2012-05-22 | 2017-07-14 | 欣凯医药化工中间体（上海）有限公司 | First ammonia folic acid compound preparation and its production and use |
| CN104546782A (en) * | 2014-10-30 | 2015-04-29 | 南京科康生物科技有限公司 | Lipoate enteric-coated micro-pill preparation and preparation method thereof |
-
2020
- 2020-10-27 EP EP20889151.5A patent/EP4061369A4/en active Pending
- 2020-10-27 WO PCT/TR2020/051001 patent/WO2021101483A1/en unknown
- 2020-10-27 CA CA3162409A patent/CA3162409A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP4061369A4 (en) | 2024-04-10 |
| WO2021101483A1 (en) | 2021-05-27 |
| EP4061369A1 (en) | 2022-09-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP3137060B2 (en) | Extended release suspension compositions | |
| US6610326B2 (en) | Divalproex sodium tablets | |
| KR101157220B1 (en) | Gastroresistant pharmaceutical formulations containing rifaximin | |
| EP3154523B1 (en) | Formulation for oral administration containing mesalazine | |
| HU204201B (en) | Coating materialdetermining delivery of active components from pharmaceutical compositions, and process for producing phrmaceutical compositions containing this coating material | |
| CA2488868A1 (en) | Controlled release formulation of lamotrigine | |
| KR101156054B1 (en) | A stable and control-released pharmaceutical composition comprising eperisone | |
| CN104013592A (en) | Memantine hydrochloride slow-release pill and preparation method thereof | |
| EA021501B1 (en) | Lipoic acid pellets | |
| CA2304135C (en) | Medicament formulation with a controlled release of an active agent | |
| CN103919715A (en) | Controlled Release Drug Combination Containing Choline Alfoscerate Or Salt Thereof And Method For Preparing Same | |
| JP5697668B2 (en) | Orally disintegrating tablets | |
| CN107753458B (en) | Nimodipine tablet medicine composition and preparation method thereof | |
| ES2663357T3 (en) | Mazindol formulations | |
| TR202016210A2 (en) | Pharmaceutical form containing acidic substance | |
| KR20230056789A (en) | Pharmaceutical composition of dapagliflozin co-crystal | |
| CN103520169A (en) | Mirtazapine tablet and preparation method thereof | |
| CN101754754B (en) | Dispersible tablet comprising coated drug-containing particles and method for the preparation thereof | |
| CN107412198A (en) | Duloxetine hydrochloride enteric slow release granule and preparation method thereof | |
| EP2358361B1 (en) | Prolonged release formulations comprising an 2-oxo-1-pyrrolidine derivate | |
| CA3162409A1 (en) | A pharmaceutical form comprising acidic substance | |
| ES2317450T3 (en) | FORMULATION OF CONTROLLED RELEASE OF VALPROIC ACID AND ITS DERIVATIVES. | |
| WO2020111089A1 (en) | Pharmaceutical composition | |
| KR101067224B1 (en) | Controlled releasing syrup containing ibuprofen and its manufacturing method | |
| US20080081069A1 (en) | Novel controlled release formulations of divalproex sodium |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20220519 |
|
| EEER | Examination request |
Effective date: 20220519 |
|
| EEER | Examination request |
Effective date: 20220519 |
|
| EEER | Examination request |
Effective date: 20220519 |
|
| EEER | Examination request |
Effective date: 20220519 |
|
| EEER | Examination request |
Effective date: 20220519 |
|
| EEER | Examination request |
Effective date: 20220519 |