WO2021222369A1 - Modified release pharmaceutical formulation comprising hydroxypropyl cellulose - Google Patents
Modified release pharmaceutical formulation comprising hydroxypropyl cellulose Download PDFInfo
- Publication number
- WO2021222369A1 WO2021222369A1 PCT/US2021/029581 US2021029581W WO2021222369A1 WO 2021222369 A1 WO2021222369 A1 WO 2021222369A1 US 2021029581 W US2021029581 W US 2021029581W WO 2021222369 A1 WO2021222369 A1 WO 2021222369A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- modified release
- release formulation
- drugs
- hydroxypropyl cellulose
- present disclosure
- Prior art date
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- 229920002153 Hydroxypropyl cellulose Polymers 0.000 title claims abstract description 137
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 title claims abstract description 137
- 239000001863 hydroxypropyl cellulose Substances 0.000 title claims abstract description 130
- 239000008194 pharmaceutical composition Substances 0.000 title description 8
- 239000000203 mixture Substances 0.000 claims abstract description 184
- 238000009472 formulation Methods 0.000 claims abstract description 164
- 239000002245 particle Substances 0.000 claims abstract description 30
- 238000006467 substitution reaction Methods 0.000 claims abstract description 21
- 239000003814 drug Substances 0.000 claims description 94
- 229940079593 drug Drugs 0.000 claims description 93
- 239000003826 tablet Substances 0.000 claims description 58
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 26
- -1 inorganic acid salts Chemical class 0.000 claims description 22
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 claims description 21
- 229960002003 hydrochlorothiazide Drugs 0.000 claims description 18
- 239000000843 powder Substances 0.000 claims description 18
- 235000000346 sugar Nutrition 0.000 claims description 15
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims description 12
- 229920002472 Starch Polymers 0.000 claims description 12
- 239000011230 binding agent Substances 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 12
- 239000008187 granular material Substances 0.000 claims description 12
- 229960001680 ibuprofen Drugs 0.000 claims description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 12
- 235000019698 starch Nutrition 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 239000007864 aqueous solution Substances 0.000 claims description 11
- 239000000314 lubricant Substances 0.000 claims description 11
- 235000010980 cellulose Nutrition 0.000 claims description 9
- 229920002678 cellulose Polymers 0.000 claims description 9
- 239000001913 cellulose Substances 0.000 claims description 9
- 239000000945 filler Substances 0.000 claims description 9
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 229930006000 Sucrose Natural products 0.000 claims description 8
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 claims description 8
- 239000005720 sucrose Substances 0.000 claims description 8
- 150000008163 sugars Chemical class 0.000 claims description 8
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 7
- 239000008101 lactose Substances 0.000 claims description 7
- 229920001223 polyethylene glycol Polymers 0.000 claims description 7
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 6
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 claims description 6
- 239000002202 Polyethylene glycol Substances 0.000 claims description 6
- 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 6
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 6
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
- 235000019359 magnesium stearate Nutrition 0.000 claims description 6
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 6
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 6
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 claims description 6
- 239000001993 wax Substances 0.000 claims description 6
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- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 5
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 5
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 5
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 5
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- 239000008117 stearic acid Substances 0.000 claims description 5
- 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 4
- 244000215068 Acacia senegal Species 0.000 claims description 4
- 108010010803 Gelatin Proteins 0.000 claims description 4
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- 230000000507 anthelmentic effect Effects 0.000 claims description 4
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- 239000002221 antipyretic Substances 0.000 claims description 4
- 239000003443 antiviral agent Substances 0.000 claims description 4
- 239000002327 cardiovascular agent Substances 0.000 claims description 4
- 229940125692 cardiovascular agent Drugs 0.000 claims description 4
- UKMSUNONTOPOIO-UHFFFAOYSA-N docosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCC(O)=O UKMSUNONTOPOIO-UHFFFAOYSA-N 0.000 claims description 4
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 claims description 4
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims description 4
- 239000004083 gastrointestinal agent Substances 0.000 claims description 4
- 229940127227 gastrointestinal drug Drugs 0.000 claims description 4
- 239000008273 gelatin Substances 0.000 claims description 4
- 229920000159 gelatin Polymers 0.000 claims description 4
- 235000019322 gelatine Nutrition 0.000 claims description 4
- 235000011852 gelatine desserts Nutrition 0.000 claims description 4
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 claims description 4
- 235000010413 sodium alginate Nutrition 0.000 claims description 4
- 239000000661 sodium alginate Substances 0.000 claims description 4
- 229940005550 sodium alginate Drugs 0.000 claims description 4
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims description 4
- 239000008107 starch Substances 0.000 claims description 4
- 239000000454 talc Substances 0.000 claims description 4
- 229910052623 talc Inorganic materials 0.000 claims description 4
- 235000012222 talc Nutrition 0.000 claims description 4
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 claims description 3
- 239000004072 C09CA03 - Valsartan Substances 0.000 claims description 3
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 3
- 229920002907 Guar gum Polymers 0.000 claims description 3
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 3
- 229930195725 Mannitol Natural products 0.000 claims description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 3
- HJLSLZFTEKNLFI-UHFFFAOYSA-N Tinidazole Chemical compound CCS(=O)(=O)CCN1C(C)=NC=C1[N+]([O-])=O HJLSLZFTEKNLFI-UHFFFAOYSA-N 0.000 claims description 3
- 239000004012 Tofacitinib Substances 0.000 claims description 3
- 229920001615 Tragacanth Polymers 0.000 claims description 3
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 3
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- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 claims description 3
- HXHWSAZORRCQMX-UHFFFAOYSA-N albendazole Chemical compound CCCSC1=CC=C2NC(NC(=O)OC)=NC2=C1 HXHWSAZORRCQMX-UHFFFAOYSA-N 0.000 claims description 3
- 229960002669 albendazole Drugs 0.000 claims description 3
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 claims description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 3
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- 239000000305 astragalus gummifer gum Substances 0.000 claims description 3
- 230000003182 bronchodilatating effect Effects 0.000 claims description 3
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 3
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- 239000002775 capsule Substances 0.000 claims description 3
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 claims description 3
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- 229960004195 carvedilol Drugs 0.000 claims description 3
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- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 claims description 3
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- OLSDWRNWUGHKSY-UHFFFAOYSA-J dicalcium;phosphonato phosphate;dihydrate Chemical compound O.O.[Ca+2].[Ca+2].[O-]P([O-])(=O)OP([O-])([O-])=O OLSDWRNWUGHKSY-UHFFFAOYSA-J 0.000 claims description 3
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 claims description 3
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- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 229960003943 hypromellose Drugs 0.000 description 1
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- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- YOBAEOGBNPPUQV-UHFFFAOYSA-N iron;trihydrate Chemical compound O.O.O.[Fe].[Fe] YOBAEOGBNPPUQV-UHFFFAOYSA-N 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- XIXADJRWDQXREU-UHFFFAOYSA-M lithium acetate Chemical compound [Li+].CC([O-])=O XIXADJRWDQXREU-UHFFFAOYSA-M 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
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- 229940057948 magnesium stearate Drugs 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 1
- 229960003987 melatonin Drugs 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
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- 235000019426 modified starch Nutrition 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
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- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
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- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
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- 229940068968 polysorbate 80 Drugs 0.000 description 1
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- 229940088417 precipitated calcium carbonate Drugs 0.000 description 1
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- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 description 1
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- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229960004029 silicic acid Drugs 0.000 description 1
- 238000004513 sizing Methods 0.000 description 1
- 238000009491 slugging Methods 0.000 description 1
- IFGCUJZIWBUILZ-UHFFFAOYSA-N sodium 2-[[2-[[hydroxy-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyphosphoryl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid Chemical compound [Na+].C=1NC2=CC=CC=C2C=1CC(C(O)=O)NC(=O)C(CC(C)C)NP(O)(=O)OC1OC(C)C(O)C(O)C1O IFGCUJZIWBUILZ-UHFFFAOYSA-N 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
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- 230000000087 stabilizing effect Effects 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
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- 238000010561 standard procedure Methods 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
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- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
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- 239000011732 tocopherol Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
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- 235000013343 vitamin Nutrition 0.000 description 1
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- 238000005406 washing Methods 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- DBRXOUCRJQVYJQ-CKNDUULBSA-N withaferin A Chemical compound C([C@@H]1[C@H]([C@@H]2[C@]3(CC[C@@H]4[C@@]5(C)C(=O)C=C[C@H](O)[C@@]65O[C@@H]6C[C@H]4[C@@H]3CC2)C)C)C(C)=C(CO)C(=O)O1 DBRXOUCRJQVYJQ-CKNDUULBSA-N 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B11/00—Preparation of cellulose ethers
- C08B11/02—Alkyl or cycloalkyl ethers
- C08B11/04—Alkyl or cycloalkyl ethers with substituted hydrocarbon radicals
- C08B11/08—Alkyl or cycloalkyl ethers with substituted hydrocarbon radicals with hydroxylated hydrocarbon radicals; Esters, ethers, or acetals thereof
-
- 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
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/549—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/5415—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L1/00—Compositions of cellulose, modified cellulose or cellulose derivatives
- C08L1/08—Cellulose derivatives
- C08L1/26—Cellulose ethers
- C08L1/28—Alkyl ethers
- C08L1/284—Alkyl ethers with hydroxylated hydrocarbon radicals
Definitions
- the presently disclosed process(es), procedure(s), method(s), product(s), result(s), and/or concept(s) (collectively referred to hereinafter as the “present disclosure”) relates generally to hydroxypropyl cellulose (HPC) and applications thereof.
- the present disclosure further relates to a modified release pharmaceutical formulation(s) derived from the hydroxypropyl cellulose.
- compositions often include polymers to achieve specific desired therapeutic effects, including for use as coating agents, film-formers, rate-controlling agents for modified release, stabilizing agents, suspending agents, tablet binders, and viscosity- increasing agents.
- an oral dosage form is the preferred route of administration of most pharmaceutical compounds because it provides easy, low cost administration.
- patient compliance is a crucial factor to consider in conjunction with oral administration of a pharmaceutical compound, especially if the compound must be taken three or four times a day.
- patient compliance it is desirable to reduce the number of daily dosage units a patient must take to attain effective therapy.
- the use of fewer, longer acting dosages also improves the constancy of drug concentrations in the blood over time, and since the drug can be closer to its ideal therapeutic dosage throughout the day, this may result in improved therapy.
- One method of accomplishing these goals is using modified release formulations, which are effective in maintaining the therapeutic blood levels over extended periods of time resulting in optimal therapy. They not only reduce the frequency of dosing, but also reduce the severity and frequency of side effects, as they maintain substantially constant blood levels and avoid the fluctuations associated with the conventional immediate release formulations administered three to four times a day.
- modified release dosage forms there are many different modified release dosage forms available commercially. Many of these modified delivery systems utilize hydrophilic, polymeric matrices that provide useful levels of control to deliver the drugs. After the formulation is ingested, the active pharmaceutical ingredient slowly releases from the polymer matrix, resulting in prolonged release of the active ingredient.
- One approach to formulating modified release compositions includes the dry blending of one or more polymers with the desired drug, forming a composition which, when exposed to fluid, forms a gel; the drug is then slowly released by diffusion from the gel.
- Tablets have been prepared in the past which will modify the release of the contained medicine, but they have not been entirely satisfactory. Some of them have been too expensive to make either because of the expensive ingredients or the complicated apparatus or process to make them or they have been too large because of the necessary additives to obtain the delayed release. Other tablets have been unsatisfactory because they have lacked a uniform release time.
- the present disclosure provides a hydroxypropyl cellulose (HPC) having a molar substitution of from about 3.0 to about 3.9, a weight average molecular weight of from about 700,000 to about 2,000,000 Daltons, and a volume average particle size of less than 100 microns.
- the molar substitution of hydroxypropyl cellulose varies in the range of from about 3.2 to about 3.8, or from about 3.4 to about 3.7.
- the weight average molecular weight of hydroxypropyl cellulose varies in the range of from about 1,000,000 to about 1,500,000 Daltons.
- the hydroxypropyl cellulose has a viscosity of least 300 mPa.s in a 1 wt.% aqueous solution at 25 °C. In another non-limiting embodiment of the present disclosure, the viscosity of hydroxypropyl cellulose can vary in the range of from about 1,000 to about 3,000 mPa.s in a 1 wi. % aqueous solution at 25 °C.
- the present disclosure provides a modified release formulation comprising hydroxypropyl cellulose having a molar substitution of from about 3.0 to about 3.9, a weight average molecular weight of from about 700,000 to about 2,000,000 Daltons, and a volume average particle size of less than 100 pm.
- the molar substitution of hydroxypropyl cellulose varies in the range of from about 3.2 to about 3.8, or from about 3.4 to about 3.7.
- the weight average molecular weight of hydroxypropyl cellulose varies in the range of from 1,000,000 to about 1,500,000 Daltons.
- the hydroxypropyl cellulose present in the modified release formulation of the present disclosure has a viscosity of at least 300 mPa.s. in a 1 wt.% aqueous solution at 25 °C.
- the viscosity of hydroxypropyl cellulose varies in the range of from about 1000 mPa.s to about 3000 mPa.s. in a ⁇ wt.% aqueous solution at 25 °C.
- the amount of hydroxypropyl cellulose in the modified release formulation varies in the range of from about 5 wt.% to about 99 wt.%, or from about 10 w/% to about 90 wt.%, or from about 15 wt.% to about 75 wt.% of the total formulation.
- the modified release formulation of the present disclosure also comprises a pharmaceutically effective amount of at least one drug having water solubility greater than 1 mg/L at 25 °C.
- the water solubility of the drug is greater than 20 mg/L, or greater than 700 mg/L.
- the drug is selected from the group consisting of antipyretic, analgesic and anti-inflammatory drugs, anthelmintic drugs, cardiovascular drugs, antibacterial drugs, bronchodilators, anti-asthmatic drugs, gastrointestinal drugs, antidiabetics, antiprotozoal drugs, antiviral drugs, anti-epileptic drugs, diuretics, or pharmaceutically acceptable salts and esters thereof.
- the drug is selected from the group consisting of etodolac, albendazole, ciprofloxacin, erythromycin and its derivative, ibuprofen, diclofenac, tofacitinib, carvedilol, metoprolol, sacubitril, valsartan, salbutamol, doxofylline, theophylline, cimetidine, omeprazole, metformin hydrochloride, sitagliptin, tinidazole, chlorothiazide, hydrochlorothiazide, acyclovir, carbamazepine, and their pharmaceutically acceptable salts and esters.
- the modified release formulation of the present disclosure further comprises at least one pharmaceutically acceptable excipient selected from the group consisting of a filler, a binder, a surfactant, a disintegrating agent, a lubricant, and a flow aid.
- the pharmaceutically acceptable excipient is a filler selected from the group consisting of monosaccharides, disaccharides, polysaccharides, and combinations thereof.
- the filler is selected from the group consisting of cellulose, lactose, sucrose, sugars, starches, processed starches, mannitol, sorbitol, xylitol, lactitol, silicic acid, calcium sulfate, aluminum and magnesium silicate complexes and oxides, calcium diphosphate dihydrate and hydrosulfates.
- the pharmaceutically acceptable excipient is a lubricant selected from the group consisting of talc, calcium stearate, magnesium stearate, polyethylene glycol, stearic acid, colloidal silicon dioxide, calcium silicate, mineral oil, wax, hydrogenated vegetable oil, glyceryl behenate, sodium benzoate, sodium acetate, sodium stearyl fumarate and combinations thereof.
- the pharmaceutically acceptable excipient is a binder selected from the group consisting of polyvinyl pyrrolidone, sucrose, lactose, starch, processed starch, sugars, gum Arabic, tragacanth gum, guar gum, pectin, wax-based binders, microcrystalline cellulose (MCC), methyl cellulose, carboxymethyl cellulose, copovidone, gelatin, sodium alginate, hydroxypropyl methyl cellulose, hydroxyethyl cellulose and combinations thereof.
- a binder selected from the group consisting of polyvinyl pyrrolidone, sucrose, lactose, starch, processed starch, sugars, gum Arabic, tragacanth gum, guar gum, pectin, wax-based binders, microcrystalline cellulose (MCC), methyl cellulose, carboxymethyl cellulose, copovidone, gelatin, sodium alginate, hydroxypropyl methyl cellulose, hydroxyethyl cellulose and combinations thereof.
- the pharmaceutical acceptable excipient is present in an amount of from about 1 wt.% to about 85 wl. %, based on the total weight of the modified release formulation.
- the modified release formulation is in the form of a tablet, a capsule, powder, granules, sachets, or lozenges.
- Fig. 1 shows an NMR spectrum of a representative Hydroxypropyl cellulose sample.
- Fig. 2 shows a dissolution profile of Hydrochlorothiazide (HCTZ) drug (as a % of the total drug released over 24 hours) present in the modified release formulation of Example 6 prepared by using 30 wt.% of Hydroxypropyl cellulose (HPC) of Example 1, and its comparison with a dissolution profile of HCTZ drug present in the Comparative modified release formulation of Example 6A prepared by using 30 wt.% of HPC of Comparative Example 5.
- HPC Hydroxypropyl cellulose
- Fig. 3 shows a dissolution profile of Hydrochlorothiazide (HCTZ) drug (as a % of the total drug released over 24 hours) present in the modified release formulation of Example 7 prepared by using 60 wt.% of HPC of Example 1, and its comparison with a dissolution profile of HCTZ drug present in the Comparative modified release formulation of Example 7A prepared by using 30 wt.% of HPC of Comparative Example 5.
- HCTZ Hydrochlorothiazide
- Fig. 4 shows a dissolution profile of Ibuprofen drug (as a % of the total drug released over 24 hours) present in the modified release formulation of Example 8 prepared by using 20 wt.% of HPC of Example 2, and its comparison with a dissolution profile of Ibuprofen drug present in the Comparative modified release formulation of Example 8 A prepared by using 20 wt.% of HPC of Comparative Example 5.
- Fig. 5 shows a dissolution profile of Ibuprofen drug (as a % of the total drug released over 24 hours) present in the modified release formulation of Example 9 prepared by using 10 wt.% of HPC of Example 2, and its comparison with a dissolution profile of Ibuprofen drug present in the Comparative modified release formulation of Example 9 A prepared by using 10 wt.% of HPC of Comparative Example 5.
- Fig. 6 shows a dissolution profile of Ibuprofen drug (as a % of the total drug released over 24 hours) present in the modified release formulation of Example 10 prepared by using 25 wt.% of HPC of Example 2, and its comparison with a dissolution profile of Ibuprofen drug present in the Comparative modified release formulation of Example 10A prepared by using 25 wt.% of HPC of Comparative Example 5.
- Fig. 7 shows a dissolution profile of Hydrochlorothiazide (HCTZ) drug (as a % of the total drug released over 24 hours) present in the modified release formulation of Example 11 prepared by using 15 wt. % of HPC of Example 3, and its comparison with a dissolution profile of the Comparative modified release formulation of Example 11A prepared by usingl5 wt.% of HPC of Comparative Example 5.
- HCTZ Hydrochlorothiazide
- Fig. 8 shows a dissolution profile of Hydrochlorothiazide (HCTZ) drug (as a % of the total drug released over 24 hours) present in the modified release formulation of Example 12 prepared by using 15 wt. % of HPC of Example 4, and its comparison with the dissolution profile of the Comparative modified release formulation of Example 11 A.
- HCTZ Hydrochlorothiazide
- inventive concept(s) Before explaining at least one embodiment of the inventive concept(s) in detail by way of exemplary drawings, experimentation, results, and laboratory procedures, it is to be understood that the inventive concept(s) is not limited in its application to the details of construction and the arrangement of the components set forth in the following description or illustrated in the drawings, experimentation and/or results.
- inventive concept(s) is/are capable of other embodiments or of being practiced or carried out in various ways.
- the language used herein is intended to be given the broadest possible scope and meaning; and the embodiments are meant to be exemplary - not exhaustive.
- phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting.
- compositions and/or methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions and/or methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the inventive concept(s) as defined by the appended claims.
- the term “at least one” will be understood to include one as well as any quantity more than one, including but not limited to, 2, 3, 4, 5, 10, 15, 20, 30, 40, 50, 100, etc.
- the term “at least one” may extend up to 100 or 1000 or more, depending on the term to which it is attached; in addition, the quantities of 100/1000 are not to be considered limiting, as higher limits may also produce satisfactory results.
- the use of the term “at least one of X, Y and Z” will be understood to include X alone, Y alone, and Z alone, as well as any combination of X, Y and Z.
- the words “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”) or “containing” (and any form of containing, such as “contains” and “contain”) are inclusive or open-ended and do not exclude additional, unrecited elements or method steps.
- A, B, C, or combinations thereof refers to all permutations and combinations of the listed items preceding the term.
- “A, B, C, or combinations thereof’ is intended to include at least one of: A, B, C, AB, AC, BC, or ABC, and if order is important in a particular context, also BA, CA, CB, CBA, BCA, ACB, BAC, or CAB.
- expressly included are combinations that contain repeats of one or more item or term, such as BB, AAA, MB, BBC, AAABCCCC, CBBAAA, CAB ABB, and so forth.
- the skilled artisan will understand that typically there is no limit on the number of items or terms in any combination, unless otherwise apparent from the context.
- drug or “active pharmaceutical ingredient(s)” or “API(s)” means any substance or mixture of substances intended to be used in the manufacture of a drug (medicinal) product and that, when used in the production of a drug product, becomes an active ingredient of the drug product. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure or function of the body of humans or other animals. Further, the terms “drug” or “active pharmaceutical ingredient(s)” or “API(s)” can be used interchangeably in the present disclosure.
- modified release in relation to the composition of the present disclosure means a composition which is not intended for immediate release and can encompasses controlled release, sustained release, prolonged release, timed release, retarded release, extended release and delayed release.
- modified release pharmaceutical formulation or “modified release dosage forms” can be described as dosage forms whose drug-release characteristics of time course and/or location are chosen to accomplish therapeutic or convenience objectives not offered by conventional dosage forms such as a solution or an immediate release dosage form.
- Modified release solid oral dosage forms include both delayed and extended release drug products (as per USFDA guideline for ‘SUPAC- MR: Modified Release Solid Oral Dosage Forms’).
- the term “Pharmaceutical Effective Amount” can describe a non-toxic and sufficient amount of the drugs that may be needed for treatment or prevention of disease, and may be adjusted depending on a variety of factors, including, but not limiting to, disease type, disease severity, the type and content of active ingredients or other ingredients contained in the formulation, dosage form, patient’s age, weight, health condition, gender and eating behavior, drug administration time, and the like. An appropriate effective amount in any individual case may be determined by one of ordinary skilled in the art using only routine experiments.
- One aspect of the present disclosure provides a hydroxypropyl cellulose (HPC) having a molar substitution number per mole of anhydrous glucose (MS) varying in the range of from about 3.0 to about 3.9 and a weight average molecular weight of from about 700,000 to about 2,000,000 Daltons.
- the molar substitution of hydroxypropyl cellulose can vary in the range of from about 3.2 to about 3.8.
- the molar substitution of hydroxypropyl cellulose can vary in the range of from about 3.4 to about 3.7.
- the weight average molecular weight of hydroxypropyl cellulose can vary in the range of from about 750,000 to about 2,000,000 Daltons or from about 800,000 to about 2,000,000 Daltons or from about 800,000 to about 1,700,000 Daltons or from about 1,000,000 to about 1,500,000 Daltons.
- the hydroxypropyl cellulose according to the present disclosure can be present in powder form and can have particles having volume average particle size of less than 100 pm.
- the volume average particle size of hydroxypropyl cellulose can vary in the range of from about 40 pm to about 80 pm or from about 50 pm to about 75 pm.
- the volume average particle size of hydroxypropyl cellulose of the present disclosure refers to a particle size D50 at the point where the cumulative volume reaches 50% in a particle size distribution obtained by performing measurements using a laser scattering particle size distribution measurement device called Malvern Mastersizer 3000.
- the hydroxypropyl cellulose (HPC) can be prepared by methods known in the related art(s) for preparing hydroxyalkyl celluloses.
- the hydroxypropyl cellulose (HPC) can be obtained by (i) reacting a raw cellulose material with an aqueous alkali solution to obtain an alkali cellulose; (ii) further reacting the alkali cellulose with propylene oxide to obtain a crude hydroxypropyl cellulose product; (iii) neutralizing the excess of alkaline solution with an aqueous acidic solution; and (iv) washing, filtering and drying the crude product to obtain a final purified hydroxypropyl cellulose product.
- the purified hydroxypropyl cellulose product can be ground further to obtain hydroxypropyl cellulose in powder form.
- 1 wt.% aqueous solution of the hydroxypropyl cellulose obtained in accordance with the present disclosure can have a viscosity of at least 300 mPa.s at 25 °C.
- the viscosity of hydroxypropyl cellulose can vary in the range of from about 300 to about 10,000 mPa.s or from about 500 to about 8,000 mPa.s or from about 1,000 to about 5,000 mPa.s or from about 1500 to about 3,000 mPa.s.
- HPC hydroxypropyl cellulose
- MS anhydrous glucose
- MS anhydrous glucose
- the molar substitution of hydroxypropyl cellulose can vary in the range of from about 3.2 to about 3.8.
- the molar substitution of hydroxypropyl cellulose can vary in the range of from about 3.4 to about 3.7.
- the weight average molecular weight of the hydroxypropyl cellulose can vary in the range of from about 750,000 to about 2,000,000 Daltons. In another non-limiting embodiment of the present disclosure, the weight average molecular weight of hydroxypropyl cellulose can vary in the range of from about 800,000 to about 2,000,000 Daltons or from about 800,000 to about 1,700,000 Daltons or from about 1,000,000 to about 1,500,000 Daltons.
- the hydroxypropyl cellulose can be present in powder form and can have particles having a volume average particle size of less than 100 pm.
- the volume average particle size of HPC can vary in the range of from about 40 to about 80 pm or from about 50 to 75 pm.
- the volume average particle size of hydroxypropyl cellulose of the present disclosure refers to a median particle size (D50) at the point where the cumulative volume reaches 50% in a particle size distribution obtained by performing measurements using a laser scattering particle size distribution measurement device called Malvern Mastersizer 3000.
- the hydroxypropyl cellulose (HPC) according to the present disclosure can be used in an amount sufficient to modify the release of at least one active pharmaceutical ingredient (API) present in the modified release formulation of the present disclosure.
- the amount of hydroxypropyl cellulose can vary in the range of from about 5 wt.% to about 99 wt.%, or from about 10 wt.% to about 90 wt.%, or from about 15 wt.% to about 75 wt.%, or from about 30 wt.% to about 60 wt.%, of the total modified release formulation.
- the modified release formulation of the present disclosure can further comprise at least one active pharmaceutical ingredient (API).
- the active pharmaceutical ingredient can be a drug.
- the active pharmaceutical ingredient (API) can be a bio-functional ingredient.
- bio-functional ingredients useful for the purpose of the present disclosure can include, but are not limited to, dietary supplements including, but not limiting to, vitamins, such as, vitamin C, vitamin Bl, B2, B3, B6, and B12; minerals, such as, zinc, magnesium, iron, and melatonin; herbal dietary supplements, such as , curcumin, ashwagandha, and fenugreek extract; amino acids, such as, isoleucine, glycine, L-tryptophan, glucosamine, chondroitin and the like. Any drugs having a wide range of water solubilities can suitably be used in the modified release formulation of the present disclosure.
- the drug can be selected from the group of drugs having a water solubility at 25 °C greater than 1 mg/L, or greater than 16 mg/L, or greater than 20 mg/L, or greater than 700 mg/L, or greater than 18,000 mg/L, or greater than 300,000 mg/L.
- the drug suitable for use in the modified release formulation of the present disclosure can be selected from those belonging to different therapeutic classes such as antipyretic, analgesic and anti-inflammatory drugs, anthelmintic drugs, cardiovascular drugs, antibacterial drugs, bronchodilating drugs, anti-asthmatic drugs, gastrointestinal drugs, antidiabetic drugs, antiprotozoal drugs, antiviral drugs, anti-epileptic drugs, anti-diuretic drugs, or its pharmaceutically acceptable salts and esters thereof.
- therapeutic classes such as antipyretic, analgesic and anti-inflammatory drugs, anthelmintic drugs, cardiovascular drugs, antibacterial drugs, bronchodilating drugs, anti-asthmatic drugs, gastrointestinal drugs, antidiabetic drugs, antiprotozoal drugs, antiviral drugs, anti-epileptic drugs, anti-diuretic drugs, or its pharmaceutically acceptable salts and esters thereof.
- Examples of the antipyretic, analgesic and anti-inflammatory drugs can include, but are not limited to, etodolac, ibuprofen, diclofenac and tofacitinib.
- Examples of the anthelminthic drugs can include, but are not limited to, albendazole.
- Examples of the cardiovascular drugs can include, but are not limited to, carvedilol, metoprolol, sacubitril and valsartan.
- Examples of antibacterial drugs can include, but are not limited to, erythromycin, ciprofloxacin or any pharmaceutically acceptable salt or ester.
- Examples of bronchodilating drugs can include, but are not limited to, salbutamol.
- anti-asthmatic drugs can include, but are not limited to, doxofylline and theophylline.
- examples of gastrointestinal drugs can include, but are not limited to, cimetidine, and omeprazole.
- examples of antidiabetic drugs can include, but are not limited to, metformin hydrochloride and sitagliptin.
- examples of antiprotozoal drugs can include, but are not limited to, tinidazole.
- antiviral drugs can include, but are not limited to, acyclovir.
- anti-epileptic drugs can include, but are not limited to, carbamazepine.
- examples of anti-diuretic drugs can include, but are not limited to, chlorothiazide and hydrochlorothiazide.
- the active pharmaceutical ingredient can be present in a pharmaceutical effective amount in the modified release formulation of the present disclosure.
- the modified release formulation of the present disclosure can be suitable for any drugs having a wide range of water solubility. Therefore, the amount of drug or drugs present in the modified release formulation of the present disclosure can be varied depending upon various factors including, but not limiting to, type of drug or drugs being used, nature and severity of the ailment being treated/cured, the type and content of active ingredients or other ingredients contained in the formulation, dosage form, patient’s age, weight, health condition, gender and eating behavior, drug administration time, and the like.
- the modified release formulation of the present disclosure can further comprise at least one pharmaceutical acceptable excipient.
- the pharmaceutical acceptable excipients which are commonly used in the pharmaceutical compositions are also suitable for use in the present modified release formulation, for example, excipients as described in Handbook of Pharmaceutical Excipients, Rows et ah, Eds., 4 th Edition, Pharmaceutical Press (2003) or Remington: The Science and Practice of Pharmacy, (formerly called Remington's Pharmaceutical Sciences), Alfonso R. Gennaro, ed., Lippincott Williams & Wilkins; 20th edition (Dec. 15, 2000).
- Examples of such excipients can include, but are not limited to, fillers, pigments, binders, lubricants, flow aids, flavors, sweeteners, preservatives, stabilizers, antioxidants, and the like.
- the pharmaceutical acceptable excipient can be present in amount without affecting the therapeutic properties of the present modified release formulation.
- the pharmaceutically acceptable excipient can comprise in the range of from about 1 wt.% to about 85 wl. %, of the total modified release formulation. In one non-liming embodiment of the present disclosure, the pharmaceutically acceptable excipient can comprise from about 5 wt.% to about 75 wt.% of the total modified release formulation, or from about 5 wt.% to about 60 wt.% of the total modified release formulation.
- fillers that can be present in the modified release formulation of the present disclosure can include, but are not limited to, cellulose; oligosaccharides, such as, lactose and sucrose; sugars; starches; processed starches; sugar alcohols, such as, mannitol, sorbitol, xylitol and lactitol; silicic acid; inorganic acid salts; calcium sulfate, and aluminum and magnesium silicate complexes and oxides.
- the inorganic acid salt excipients can include, but are not limited to, phosphoric salts such as calcium diphosphate dihydrate and hydrosulfates.
- the fillers can be present in an amount of from about 5.0 wt.% to about 15 MV. % of the total modified release formulation.
- binders that can be present in the modified release formulation of the present disclosure can include, but are not limited to, polyvinyl pyrrolidone (PVP), sucrose, lactose, starches, processed starches, sugars, gum arabic, tragacanth gum, guar gum, pectin, wax-based binders, microcrystalline cellulose (MCC), methylcellulose, carboxymethylcellulose, copovidone, gelatin and sodium alginate.
- PVP polyvinyl pyrrolidone
- MMC microcrystalline cellulose
- the binders can be present in an amount of from about 1 wt.% to about 80 wt.% of the total modified release formulation.
- suitable lubricants that can be present in the modified release formulation of the present disclosure can include, but are not limited to, magnesium stearate, stearic acid, palmitic acid, calcium stearate, talc, carnauba wax, hydrogenated vegetable oils, mineral oils, polyethylene glycol, sodium stearyl fumarate and sucrose fatty acid esters of acids such as stearic acid, palmitic acid, myristic acid, oleic acid, lauric acid, behenic acid, erucic acid and the like. Further, the lubricants can be present in an amount of from about 0.1 wt.% to about 20 wt.% of the total modified release formulation.
- the modified release formulation of the present disclosure can further comprise at least one additional modifying release agent.
- additional modifying release agent can include, but are not limited to, sodium alginate, carboxy vinyl polymers, acrylic acid-based polymers such as aminoalkyl methacrylate copolymer RS (Eudragit RS , manufactured by Rohm Pharma GmbH) and ethyl acrylate-methyl methacrylate copolymer suspension (Eudragit NE , manufactured by Rohm Pharma GmbH).
- the additional modifying release agent can be present in an amount of from about 5 wt.% to about 50 wt.%, of the total modified release formulation.
- pH regulators suitable for use in the modified release formulation of the present disclosure can be inorganic acids, such as hydrochloric acid, sulfuric acid, hydrobromic acid and phosphoric acid; organic acids, such as acetic acid, succinic acid, fumaric acid, malic acid, oxalic acid, lactic acid, glutaric acid, salicylic acid and tartaric acid, and salts thereof; or any combinations thereof.
- inorganic acids such as hydrochloric acid, sulfuric acid, hydrobromic acid and phosphoric acid
- organic acids such as acetic acid, succinic acid, fumaric acid, malic acid, oxalic acid, lactic acid, glutaric acid, salicylic acid and tartaric acid, and salts thereof; or any combinations thereof.
- colorants or food dyes such as food yellow No. 5, food red No. 2 and food blue No. 2, food lake dyes, or iron sesquioxide
- pH buffers such as amine-based buffers or carbonate-based buffers
- surfactants such as sodium lauryl sulfate, polysorbate 80, hydrogenated oil, or polyoxyethylene (160) polyoxypropylene (30) glycol
- stabilizers such as tocopherol, tetrasodium edetate, nicotinamide or cyclodextrins
- acidifiers such as citric acid, tartaric acid, malic acid or ascorbic acid.
- the modified release formulation of the present disclosure can be present in a dry solid dosage form.
- the dry solid dosage forms are particularly useful for delivering an accurate dosage to a specific site, usually orally, but can also be administered via other routes that are known to a person skilled in the pertinent art, such as sublingual/buccal, rectal, vaginal and ocular.
- the modified release formulation can be present in a solid dosage form suitable for oral administration.
- dosage forms can include, but are not limited to, tablets, capsules, powder, granules, sachets or lozenges.
- the modified release formulation is tablets.
- the tablet form of the modified release formulation of the present disclosure can be coated with base materials for the purpose of masking a smell or taste, stabilizing, maintaining efficacy and the like.
- the coating can comprise sugars or film forming polymers.
- the tablets can be sugar coated, film coated, enteric coated or coated with a thin layer or a film of modifying release agents to further modify the release of the drugs/active pharmaceutical ingredients from the formulation.
- the tablets can be sugar coated.
- the sugar coatings of tablets is/are basically a thick and hard coatings of sugars surroundings the surface of the tablets which is desirable to hide the flavor of a particular unpleasant tasting drugs or any other active pharmaceutical ingredients, and also to provide stability to tablets from breaking under the effect of light and moisture.
- the sugar coating of the tablets according to the present disclosure can be carried out using a sugar base material.
- the sugar base material useful for the purpose of the present disclosure can include, but are not limited to, white soft sugar. Additional pharmaceutically acceptable excipient(s) can also be added in the sugar base materials to enhance the properties of the sugar base coating such as improved binding ability and mechanical strength, and anti-sticking property.
- additional excipients can include, but are not limited to, gelatin, gum arabic, polyvinylpyrrolidone, pullulan, talc, precipitated calcium carbonate, calcium phosphate, calcium and the like.
- the sugar-base coating can also comprise flavorants or colorants/pigments as additional pharmaceutical excipients.
- the tablets can be film coated.
- the film coating of tablets in general includes enveloping of tablet’s core with a thin film of protective polymers.
- the tablet of the present disclosure can comprise thin film of polymers, particularly water-soluble film-based polymers as a coating layer. Both synthetic as well as natural polymers can be used for tablet film coating.
- Examples of synthetic polymer can include, but are not limited to, polyvinyl alcohol, polyvinyl alcohol-polyethylene glycol graft copolymers, polyvinyl alcohol-acrylic acid-methyl methacrylate copolymers, polyvinyl acetal diethylamino acetate, aminoalkyl methacrylate copolymers, polyvinylpyrrolidone and macrogol.
- Examples of natural polymers can include, but are not limited to, polysaccharides such as pullulan.
- the tablets can be enteric film coated.
- the enteric film coating on tablets is desirable to protect the stomach from the tablet formulation; protect the drugs against stomach acids, and to release the active pharmaceutical ingredients in specific locations which is usually lower area of stomach or intestines.
- the enteric film coating of the present tablets can be carried out using enteric film coating base materials. Examples of such materials can include, but are not limited to, acrylic acid derivatives such as methacrylic acid copolymer L, methacrylic acid copolymer LD and methacrylic acid copolymer S; and natural materials such as shellac.
- the tablet form of the modified release formulation of the present disclosure can be coated with a thin layer or a film of a modifying release agent to further enhance or improve the modifying release efficiency of the present modified release formulation.
- tablets of the present disclosure can be coated with a thin layer or film of the present modified release formulation, or a thin layer or film of an additional modifying release agent, or combination of both.
- the tablets can be coated with a thin layer or a film of the modified release formulation of the present disclosure.
- the modified release formulation used for coating purpose can further comprises at least one of the coating materials used for sugar coating, film coating, and enteric coating, as hereinabove described in the present disclosure.
- the tablets can be coated with a thin layer or film of an additional modified release agent.
- additional modified release agent can include, but are not limited to, Hypromellose, polyethylene oxide, hydroxyethyl cellulose, ethyl cellulose, methacrylic acid copolymers, guar, xanthan, alginates, starch derivatives, waxes and fats.
- the coating materials used for the purpose of the present disclosure can further comprise at least one of the pharmaceutically acceptable excipients described herein above in the present disclosure, such as binders, lubricants, plasticizers, stabilizers, colorants and the like.
- modified release formulation of the present disclosure there is no limitation regarding the method employed for preparing the modified release formulation of the present disclosure, particularly the modified release formulation in the solid oral dosage form such as tablets.
- Any tableting methods which are well known in the pharmaceutical art such as wet granule tableting method or a dry granule tableting method or a dry direct tableting method can suitably be used for the purpose of the present disclosure.
- the modified release formulation in tablets form can be prepared by a wet granulation method wherein the method comprising the steps of (i) blending a mixture of hydroxypropyl cellulose, the active pharmaceutical ingredients such as drug(s) and other required pharmaceutical acceptable excipients to make a uniform homogenous blend; (ii) adding a wetting agent to obtain a kneaded blend followed by granulating the same to obtain resultant granules; (iii) drying and sizing the resultant granules to an optimum size suitable for compression; (iv) blending the sized granules obtained from process step (iii) with a suitable pharmaceutical acceptable lubricant such as magnesium stearate; and finally (v) compressing the blended granules obtained from the process step (iv) into tablets.
- a wet granulation method comprising the steps of (i) blending a mixture of hydroxypropyl cellulose, the active pharmaceutical ingredients such as drug(s) and other required pharmaceutical acceptable ex
- the modified release formulation of the present disclosure can be prepared by a dry granulation method comprising the steps of: (i) dispensing and mixing pre-determined amounts of various ingredients of the modified release formulation of the present disclosure such as hydroxypropyl cellulose, the active pharmaceutical ingredients and the pharmaceutical acceptable excipients to obtain a uniform powder blend; (ii) subjecting the uniform powder blend to compression either by slugging or roller compaction to obtain flat large tablets or pellets; (iii) milling and sieving the flat large tablets or pellets to obtain uniform granules; and (iv) subjecting the granules to tablet compression.
- Lubricants such as magnesium stearate and other excipients such as disintegrants, glidants and the like can also be added in the uniform granules before subject the same to tablet compression.
- the modified release formulation of the present disclosure can be prepared by a dry direct tableting method or a directly compressible method comprising the steps of (i) pre-milling or sieving various ingredients of the modified release formulation of the present disclosure such as hydroxypropyl cellulose, the active pharmaceutical ingredients such as drug(s) and the pharmaceutical acceptable excipients including lubricant to obtain powdered ingredients; (ii) uniformly blending or mixing the powdered ingredients to obtain a homogenous blend; and (iii) subjecting the homogenous blend to tablet compression to obtain tablets.
- a dry direct tableting method or a directly compressible method comprising the steps of (i) pre-milling or sieving various ingredients of the modified release formulation of the present disclosure such as hydroxypropyl cellulose, the active pharmaceutical ingredients such as drug(s) and the pharmaceutical acceptable excipients including lubricant to obtain powdered ingredients; (ii) uniformly blending or mixing the powdered ingredients to obtain a homogenous blend; and (iii) subjecting the homogenous
- the hydroxypropyl cellulose present in the modified release formulation can provide low dose dumping of the active pharmaceutical ingredient(s), (ii) can uniformly release the active pharmaceutical ingredient(s) over a period of time, (iii) can provide effective tablet compaction properties, and (iv) can provide controlled release of the active pharmaceutical ingredient at a lower polymer usage levels.
- Examples 1-4 of the present disclosure provides hydroxypropyl celluloses (HPC) of the present disclosure.
- Example 1 Preparation of Hydroxypropyl Cellulose (HPC) with HP -MS of 3 72
- the solvent was removed by filtration, and the product was then washed with hot water and filtered to remove salts and impurities.
- the purified cake thus obtained was dried at about 130 - 140°C until ⁇ 5% moisture was reached.
- the dried hydroxypropyl cellulose thus obtained was ground until hydroxypropyl cellulose in powder form having particles of D50 ⁇ 100 pm was obtained.
- the hydroxypropyl molar substitution was analyzed as 3.7.
- the Mw was 1,510,000 Daltons, and the aqueous solution viscosity was 1,800 mPa.s at 1 wt.% in water.
- the volume- average particle size (D50) was 52 pm.
- Example 2 (Ex 2): Preparation of HPC with HP -MS 3 72
- HPC of this example was prepared in the same manner as described for Example 1 except that 2.8 parts of propylene oxide was used.
- Example 3 (Ex 3): Preparation of HPC with HP -MS 3 56
- HPC of this example was prepared using the procedure described in Example 1 except that 2.0 parts of propylene oxide was used.
- Example 4 (Ex 4): Preparation of HPC with HP -MS: 3 56
- HPC of this example was prepared in the same manner as described for Example 1 except that 2.1 parts of propylene oxide was used.
- hydroxypropyl cellulose of Examples 1-4 and Comparative Example 5 were measured for hydroxypropyl molar substitution (HP -MS), molecular weight (MW) distribution, viscosity, and a volume average particle size as per the testing methods given below. The measured values are given in Table 1.
- HP -MS value of the HPCs of Examples 1-4 and Comparative Example 5 was determined by NMR as follows:
- Sample hydrolysis 25 mg of sample was initially swelled in 1.00 gm of D2O for 30 mins. To the swelled sample, 0.5 gm of 35% DC1 was added. The solution vial was maintained at 70 °C for 1 hour in a heat block. The sample solution was cool down for ⁇ 30 minutes and transferred to 5 mm NMR tube for analysis.
- Region A (IA) 1.90-0.15 ppm (integral area was calibrated to a value of 300, other integral areas were relative to this integral value).
- Region B (IB) 5.70-2.15 ppm.
- the particle size of the powder form of hydroxypropyl celluloses of Examples 1-4 and Comparative Example 5 was measured by using the Malvern Mastersizer 3000 laser diffraction particle size analyzer. The measurements were done on samples in powder form using the Aero S dry powder feeder equipped with a general-purpose hopper/sample tray pair and a standard stainless-steel venturi powder dispenser. The Aero S hopper gap was set to 4.0 mm. Powder sample was measured by completely filling a 1 ⁇ 4 teaspoon measuring spoon and loaded into the hopper. The powder feed rate was set to 30%, and the air pressure was set to 3.0 bar. The obscuration limits were set to 0.2% low limit and 10% high limit with obscuration filtering turned off.
- the background measurement time was set to 10 seconds and the sample measurement time was set to 20 seconds, with the measurement set to start once the obscuration was within the set range and after a stabilization time of 0.1 seconds.
- the Fraunhofer scattering model and the “General Purpose” analysis model were used for data analysis, which were converted to particle diameter using the volume distribution
- Nisso HPC H having a molecular weight of 652,000, a 1 wt.% aqueous solution viscosity of 146 mPa.s at 25 °C, and a particle size D50 of 170 pm is expected to exhibit poorer modified drug release performance than the HPC of the present disclosure.
- Molecular weight, viscosity and particle size of the Nisso HPC H were measured as per the testing methods described hereinabove.
- hydroxypropyl celluloses of the present Examples 1 - 4 are used further in the modified release formulations along with drug(s) and other pharmaceutical acceptable excipients.
- Table 2 lists drugs used for producing the present modified release formulations.
- Example 6 Modified release formulation (Ex 6) having 30 wt.% HPC of Example 1
- Hydrochlorothiazide, HPC of Example 1, and spray dried lactose (Ingredient 1-3) were weighed in weight proportion listed in Table 3, screened through a USP sieve#20, and blended in a Turbula mixer for 10 minutes.
- Sodium stearyl fumarate, colloidal silicon dioxide and magnesium stearate were also weighed separately, screened through a USP sieve#20 and added into the blend of Ingredients 1-3. This resulting powder blend thus obtained was again blended for 2 minutes in a Turbula mixer to obtain a homogenous powder blend.
- the homogenous powder blend was then compressed into tablets using a compaction simulator STYL’one, simulating manesty beta press operating at a press speed of 67 RPM (64320 tablets/hour), using 11.28 flat faced punches and die at a compaction force of 25 kN. Tablets with individual tablet weight of approximate 500 mg were obtained.
- Example 6 A Comparative modified release formulation (Ex.6 A) having 30 wt.% HPC of Comparative Example 5
- a comparative modified release formulation (Ex.6A) using 30.0 wt.% HPC of Comparative Example 5 was prepared in the same manner as described above in Example 6 using the ingredients in amounts listed in Table 3 above.
- Fig. 2 shows the dissolution profile of Hydrochlorothiazide (HCTZ) as a % of the total drug released over 24 hours for both the formulations i.e.6 and Ex.6A. It is evident from Fig. 2 that the drug release from the modified release formulation of Example 6 was slower than the drug release from the comparative modified release formulation of Example 6A.
- HCTZ Hydrochlorothiazide
- Example 7 Modified release formulation (Ex 7) having 60 wt.% HPC of Example 1 [0094] A modified release formulation (Ex.7) comprising 60 wt.% HPC of Example 1 was prepared in this example. The modified release formulation of this example was prepared in the same manner as described above in Example 6 using the ingredient in amounts listed in Table 4 below.
- Example 7 A Comparative modified release formulation (Ex.7 A) having 60 wt.% HPC of Comparative Example 5
- a control modified release formulation (Ex.7 A) comprising 60.0 wt.% of HPC of Comparative Example 5 was prepared in the same manner as described above for the modified release formulation of Example 7 using the ingredients in amounts listed in Table 4 above.
- Fig. 3 shows the dissolution profile of Hydrochlorothiazide (HCTZ) as a % of the total drug released over 24 hours for both the formulations i.e. Ex.7 and Ex.7A. It is evident from Fig. 3 that the drug release from the modified release formulation of Example 7 was slower than the comparative modified release formulation of Example 7 A.
- HCTZ Hydrochlorothiazide
- Example 8 Modified release formulation (Ex 8) having 20 wt.% HPC of Example 2 [0097]
- modified release formulation tablets (Ex.8) of individual tablet weight of approximately 860 mg were prepared using 20 wt.% HPC of Example 2.
- the modified release formulation (Ex.8) of this example was prepared in the same manner as described above in Example 6 using the ingredient in amounts listed in Table 5 below.
- Example 8 A Comparative modified release formulation (Ex.8 A) having 20 wt.% HPC of Comparative Example 5
- a comparative modified release formulation comprising 20.0 wt.% HPC of Comparative Example 5 was prepared in the same manner as described above for the modified release formulation of Example 8 using the ingredients in amounts listed in Table 5 above.
- the samples were analyzed by inline UV detection at 221 nm.
- Fig. 4 shows the dissolution profile of Ibuprofen as a % of the total drug released over 24 hours for both the formulations i.e. Ex.8 and Ex.8A.
- the drug release from the modified release formulation of Example 8 was slower than the drug release from the comparative modified release formulation of Example 8 A.
- Example 9 Modified release formulation (Ex.9) having 10 wt.% HPC of Example 2
- Example 8 Similar to the formulation of Example 8, this example describes a preparation of modified release formulation with individual tablet weight of approximate 860 mg using the same ingredients and procedure as described in Example 8, except that 10 wt.%. HPC of Example 2 was used. Accordingly, the weight proportion of other ingredients were adjusted and listed in Table 6 below.
- Example 9A Comparative modified release formulation (Ex.9A) having 10 wt.% HPC of Comparative Example 5
- a comparative modified release formulation comprising 10.0 wt.% of HPC of Comparative Example 5 was prepared in the same manner as described above for the modified release formulation of Example 9 using the ingredients in amounts listed in Table 6 above.
- the samples were analyzed by inline UV detection at 221 nm.
- Fig. 5 shows the dissolution profile of Ibuprofen as a % of total drug released over 24 hours for both the formulations, Ex.9 and Ex.9A.
- the drug release from the modified release formulation of Example 9 was slower than the drug release from the comparative modified release formulation of Example 9 A.
- Example 10 Modified release formulation (Ex.10) having 25 wt.% HPC of Example 2
- modified release formulation tablets (Ex.10) of individual tablet weight of approximately 500 mg were prepared using 25 wt.% HPC of Example 2.
- the modified release formulation (Ex.10) of this example was prepared using the ingredient in amounts listed in Table 7 below and in the same manner as described above in Example 6.
- Example 10 A Comparative modified release formulation (Ex.10 A) having 25 wt.% HPC of Comparative Example 5
- a comparative modified release formulation comprising 25.0 wt.% of HPC of Comparative Example 5 was also prepared in the same manner as described above for the modified release formulation of Example 10 using the ingredients in amounts listed in Table 7 above.
- the samples were analyzed by inline UV detection at 221 nm.
- Fig. 6 shows the dissolution profile of Ibuprofen as a % of the total drug released over 24 hours for both the formulations i.e. Ex.10 and Ex.lOA.
- the drug release from the modified release formulation of Example 10 was slower than the drug release from the comparative modified release formulation of Example 10 A.
- Example 11 Modified release formulation (Ex 11) having 15 wt.% HPC of Example 3
- Modified release formulation tablets with individual tablet weight of approximately 500mg were prepared in this example using 15 wt.% HPC of Example 3.
- the tablets were prepared in the same manner as described above in Example 6 using the ingredients in amounts listed in Table 8 below.
- Example 11 A Comparative modified release formulation (Ex 11 A) having 15 wt.% HPC of Comparative Example 5
- a comparative modified release formulation comprising 15.0 wt.% of HPC of Comparative Example 5 was prepared in the same manner as described above for the modified release formulation of Example 11 using the ingredients in amounts listed in Table 8 above.
- the dissolution profile of the modified release formulation of Example 11 (Ex.11) was shown in Fig. 7 and compared with the dissolution profile of the comparative modified release formulation of Example 11 A.
- the drug release from the modified release formulation of Example 11 (Ex.11) was slower than the drug release from the comparative modified release formulation of Example 11A (Ex.11 A).
- Example 12 Modified release formulation (Ex.12) having 15 wt.% of HPC of Example 4.
- Modified release formulation tablets with individual tablet weight of approximately 500 mg were prepared in this example using 15 wt.% HPC of Example 4.
- the tablets were prepared in the same manner as described above in Example 6 using the ingredients in amounts listed in Table 9 below.
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- Biochemistry (AREA)
- Materials Engineering (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Preparation (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
Claims
Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202180045957.6A CN115996718A (en) | 2020-05-01 | 2021-04-28 | Modified release pharmaceutical formulation comprising hydroxypropyl cellulose |
IL297810A IL297810A (en) | 2020-05-01 | 2021-04-28 | Modified release pharmaceutical formulation comprising hydroxypropyl cellulose |
KR1020227041714A KR20230005317A (en) | 2020-05-01 | 2021-04-28 | Modified Release Pharmaceutical Formulations Comprising Hydroxypropyl Cellulose |
CA3176772A CA3176772A1 (en) | 2020-05-01 | 2021-04-28 | Modified release pharmaceutical formulation comprising hydroxypropyl cellulose |
MX2022013552A MX2022013552A (en) | 2020-05-01 | 2021-04-28 | Modified release pharmaceutical formulation comprising hydroxypropyl cellulose. |
EP21795764.6A EP4142718A4 (en) | 2020-05-01 | 2021-04-28 | Modified release pharmaceutical formulation comprising hydroxypropyl cellulose |
JP2022566421A JP2023524517A (en) | 2020-05-01 | 2021-04-28 | Modified release formulation containing hydroxypropyl cellulose |
BR112022022107A BR112022022107A2 (en) | 2020-05-01 | 2021-04-28 | MODIFIED RELEASE PHARMACEUTICAL FORMULATION COMPRISING HYDROXYPROPYLCELLULOSE |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US202063019215P | 2020-05-01 | 2020-05-01 | |
US63/019,215 | 2020-05-01 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2021222369A1 true WO2021222369A1 (en) | 2021-11-04 |
Family
ID=78373905
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2021/029581 WO2021222369A1 (en) | 2020-05-01 | 2021-04-28 | Modified release pharmaceutical formulation comprising hydroxypropyl cellulose |
Country Status (9)
Country | Link |
---|---|
EP (1) | EP4142718A4 (en) |
JP (1) | JP2023524517A (en) |
KR (1) | KR20230005317A (en) |
CN (1) | CN115996718A (en) |
BR (1) | BR112022022107A2 (en) |
CA (1) | CA3176772A1 (en) |
IL (1) | IL297810A (en) |
MX (1) | MX2022013552A (en) |
WO (1) | WO2021222369A1 (en) |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090155409A1 (en) * | 2007-12-17 | 2009-06-18 | Sexton Frederick A | Sustained release of nutrients in vivo |
-
2021
- 2021-04-28 IL IL297810A patent/IL297810A/en unknown
- 2021-04-28 BR BR112022022107A patent/BR112022022107A2/en unknown
- 2021-04-28 EP EP21795764.6A patent/EP4142718A4/en active Pending
- 2021-04-28 WO PCT/US2021/029581 patent/WO2021222369A1/en active Application Filing
- 2021-04-28 CA CA3176772A patent/CA3176772A1/en active Pending
- 2021-04-28 MX MX2022013552A patent/MX2022013552A/en unknown
- 2021-04-28 KR KR1020227041714A patent/KR20230005317A/en active Search and Examination
- 2021-04-28 CN CN202180045957.6A patent/CN115996718A/en active Pending
- 2021-04-28 JP JP2022566421A patent/JP2023524517A/en active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090155409A1 (en) * | 2007-12-17 | 2009-06-18 | Sexton Frederick A | Sustained release of nutrients in vivo |
Non-Patent Citations (6)
Title |
---|
ANONYMOUS: "4-Aminobenzoic acid ", WIKIPEDIA, 7 December 2019 (2019-12-07), pages 1 - 6, XP055869399, Retrieved from the Internet <URL:https://en.wikipedia.org/w/index.php?title=4-Aminobenzoic_acid&oldid=929697094> [retrieved on 20211206] * |
ANONYMOUS: "Glucose", WIKIPEDIA, 17 December 2019 (2019-12-17), pages 1 - 17, XP055869400, Retrieved from the Internet <URL:https://en.wikipedia.org/w/index.php?title=Glucose&oldid=931205731> [retrieved on 20211206] * |
ANONYMOUS: "Poise (unit) ", WIKIPEDIA, 3 July 2019 (2019-07-03), pages 1 - 2, XP055869392, Retrieved from the Internet <URL:https://en.wikipedia.org/w/index.php?titie=Poise_(unit)&oldid=904652824> [retrieved on 20211206] * |
ANONYMOUS: "Theophylline", WIKIPEDIA, 25 February 2019 (2019-02-25), pages 1 - 9, XP055869402, Retrieved from the Internet <URL:https://en.wikipedia.org/w/index.php?title=Theophylline&oldid=884943148> [retrieved on 20211206] * |
BROOKHAVEN INSTRUMENTS CORPORATION: "A Guide to Particle Size Distribution Weighting", AZOM.COM, 11 June 2019 (2019-06-11), pages 1 - 8, XP055869391, Retrieved from the Internet <URL:https://www.azom.com/article.aspx?ArticleID=18150> [retrieved on 20211206] * |
See also references of EP4142718A4 * |
Also Published As
Publication number | Publication date |
---|---|
MX2022013552A (en) | 2022-11-30 |
JP2023524517A (en) | 2023-06-12 |
BR112022022107A2 (en) | 2023-02-28 |
EP4142718A4 (en) | 2024-05-29 |
EP4142718A1 (en) | 2023-03-08 |
KR20230005317A (en) | 2023-01-09 |
CN115996718A (en) | 2023-04-21 |
CA3176772A1 (en) | 2021-11-04 |
IL297810A (en) | 2022-12-01 |
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