WO2012026908A2 - Cefpodoxime proxetil formulations comprising taste regulating agent - Google Patents
Cefpodoxime proxetil formulations comprising taste regulating agent Download PDFInfo
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- WO2012026908A2 WO2012026908A2 PCT/TR2011/000201 TR2011000201W WO2012026908A2 WO 2012026908 A2 WO2012026908 A2 WO 2012026908A2 TR 2011000201 W TR2011000201 W TR 2011000201W WO 2012026908 A2 WO2012026908 A2 WO 2012026908A2
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- WIPO (PCT)
- Prior art keywords
- pharmaceutical composition
- composition according
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- sodium
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- 229960004797 cefpodoxime proxetil Drugs 0.000 title claims abstract description 16
- LTINZAODLRIQIX-FBXRGJNPSA-N cefpodoxime proxetil Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC)C(=O)OC(C)OC(=O)OC(C)C)C(=O)C(=N/OC)\C1=CSC(N)=N1 LTINZAODLRIQIX-FBXRGJNPSA-N 0.000 title claims abstract description 15
- 239000000203 mixture Substances 0.000 title claims description 49
- 238000009472 formulation Methods 0.000 title claims description 37
- 235000019640 taste Nutrition 0.000 title claims description 12
- 230000001105 regulatory effect Effects 0.000 title claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 42
- 235000002639 sodium chloride Nutrition 0.000 claims description 41
- 239000008187 granular material Substances 0.000 claims description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 38
- 150000003839 salts Chemical class 0.000 claims description 36
- 239000003826 tablet Substances 0.000 claims description 36
- 239000003795 chemical substances by application Substances 0.000 claims description 32
- 239000000843 powder Substances 0.000 claims description 31
- WYUSVOMTXWRGEK-HBWVYFAYSA-N cefpodoxime Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC)C(O)=O)C(=O)C(=N/OC)\C1=CSC(N)=N1 WYUSVOMTXWRGEK-HBWVYFAYSA-N 0.000 claims description 27
- 229960005090 cefpodoxime Drugs 0.000 claims description 26
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 20
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 18
- 150000002016 disaccharides Chemical class 0.000 claims description 17
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 claims description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 12
- 239000013543 active substance Substances 0.000 claims description 12
- 229960003324 clavulanic acid Drugs 0.000 claims description 12
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 12
- 235000003599 food sweetener Nutrition 0.000 claims description 11
- 239000003765 sweetening agent Substances 0.000 claims description 11
- 239000008122 artificial sweetener Substances 0.000 claims description 10
- 235000021311 artificial sweeteners Nutrition 0.000 claims description 10
- 150000004677 hydrates Chemical class 0.000 claims description 10
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
- 239000012453 solvate Substances 0.000 claims description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 8
- 230000002378 acidificating effect Effects 0.000 claims description 8
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 8
- 239000007884 disintegrant Substances 0.000 claims description 8
- 239000003906 humectant Substances 0.000 claims description 8
- 239000000314 lubricant Substances 0.000 claims description 8
- 229960001866 silicon dioxide Drugs 0.000 claims description 8
- 229920002472 Starch Polymers 0.000 claims description 7
- -1 glidant Substances 0.000 claims description 7
- 239000000377 silicon dioxide Substances 0.000 claims description 7
- 239000008107 starch Substances 0.000 claims description 7
- 235000019698 starch Nutrition 0.000 claims description 7
- 239000000454 talc Substances 0.000 claims description 7
- 229910052623 talc Inorganic materials 0.000 claims description 7
- 235000012222 talc Nutrition 0.000 claims description 7
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 6
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 6
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- 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 6
- 239000011230 binding agent Substances 0.000 claims description 6
- 235000015165 citric acid Nutrition 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 6
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 6
- 229920000609 methyl cellulose Polymers 0.000 claims description 6
- 239000001923 methylcellulose Substances 0.000 claims description 6
- 235000010981 methylcellulose Nutrition 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 6
- 235000011181 potassium carbonates Nutrition 0.000 claims description 6
- ABVRVIZBZKUTMK-JSYANWSFSA-M potassium clavulanate Chemical compound [K+].[O-]C(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 ABVRVIZBZKUTMK-JSYANWSFSA-M 0.000 claims description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 239000003755 preservative agent Substances 0.000 claims description 6
- 235000012239 silicon dioxide Nutrition 0.000 claims description 6
- 239000011780 sodium chloride Substances 0.000 claims description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 6
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 5
- 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
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 4
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims description 4
- 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 4
- 108010011485 Aspartame Proteins 0.000 claims description 4
- QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 0.000 claims description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 4
- 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 4
- 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 4
- 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 4
- 239000001856 Ethyl cellulose Substances 0.000 claims description 4
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 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
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 4
- 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 4
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 4
- 229930006000 Sucrose Natural products 0.000 claims description 4
- 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 4
- 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 4
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 4
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 claims description 4
- 239000000605 aspartame Substances 0.000 claims description 4
- 235000010357 aspartame Nutrition 0.000 claims description 4
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 4
- 229960003438 aspartame Drugs 0.000 claims description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 claims description 4
- 239000001175 calcium sulphate Substances 0.000 claims description 4
- 235000011132 calcium sulphate Nutrition 0.000 claims description 4
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 claims description 4
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 claims description 4
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 4
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 4
- 229920001249 ethyl cellulose Polymers 0.000 claims description 4
- 239000000796 flavoring agent Substances 0.000 claims description 4
- 235000013355 food flavoring agent Nutrition 0.000 claims description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 4
- 229940071676 hydroxypropylcellulose Drugs 0.000 claims description 4
- 229960003943 hypromellose Drugs 0.000 claims description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 4
- 239000008101 lactose Substances 0.000 claims description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 4
- 239000001630 malic acid Substances 0.000 claims description 4
- 235000011090 malic acid Nutrition 0.000 claims description 4
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 4
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 4
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 4
- 239000011736 potassium bicarbonate Substances 0.000 claims description 4
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 claims description 4
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 4
- 229940069328 povidone Drugs 0.000 claims description 4
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 claims description 4
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 4
- 239000004299 sodium benzoate Substances 0.000 claims description 4
- 235000010234 sodium benzoate Nutrition 0.000 claims description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 4
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- 235000017550 sodium carbonate Nutrition 0.000 claims description 4
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 claims description 4
- 239000000600 sorbitol Substances 0.000 claims description 4
- 235000010356 sorbitol Nutrition 0.000 claims description 4
- 239000005720 sucrose Substances 0.000 claims description 4
- 235000002906 tartaric acid Nutrition 0.000 claims description 4
- 239000011975 tartaric acid Substances 0.000 claims description 4
- 235000019731 tricalcium phosphate Nutrition 0.000 claims description 4
- 239000004552 water soluble powder Substances 0.000 claims description 4
- 239000004554 water soluble tablet Substances 0.000 claims description 4
- 208000015181 infectious disease Diseases 0.000 claims description 3
- 239000000395 magnesium oxide Substances 0.000 claims description 3
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 3
- 239000000391 magnesium silicate Substances 0.000 claims description 3
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims description 3
- 239000000725 suspension Substances 0.000 claims description 3
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims description 2
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 claims description 2
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- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 2
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- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 claims description 2
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- 239000000832 lactitol Substances 0.000 claims description 2
- 235000010448 lactitol Nutrition 0.000 claims description 2
- VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 claims description 2
- 229960003451 lactitol Drugs 0.000 claims description 2
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 2
- 239000001095 magnesium carbonate Substances 0.000 claims description 2
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims description 2
- 229910052919 magnesium silicate Inorganic materials 0.000 claims description 2
- 235000019792 magnesium silicate Nutrition 0.000 claims description 2
- 235000019359 magnesium stearate Nutrition 0.000 claims description 2
- 239000000845 maltitol Substances 0.000 claims description 2
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 claims description 2
- 235000010449 maltitol Nutrition 0.000 claims description 2
- 229940035436 maltitol Drugs 0.000 claims description 2
- 229940035034 maltodextrin Drugs 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 2
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 claims description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 claims description 2
- 229960002900 methylcellulose Drugs 0.000 claims description 2
- 229960002216 methylparaben Drugs 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- 235000005985 organic acids Nutrition 0.000 claims description 2
- 235000011007 phosphoric acid Nutrition 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 2
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 2
- 239000004300 potassium benzoate Substances 0.000 claims description 2
- 235000010235 potassium benzoate Nutrition 0.000 claims description 2
- 229940103091 potassium benzoate Drugs 0.000 claims description 2
- 239000001103 potassium chloride Substances 0.000 claims description 2
- 235000011164 potassium chloride Nutrition 0.000 claims description 2
- 239000001508 potassium citrate Substances 0.000 claims description 2
- 229960002635 potassium citrate Drugs 0.000 claims description 2
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 claims description 2
- 235000011082 potassium citrates Nutrition 0.000 claims description 2
- 239000011698 potassium fluoride Substances 0.000 claims description 2
- 235000003270 potassium fluoride Nutrition 0.000 claims description 2
- 229940086066 potassium hydrogencarbonate Drugs 0.000 claims description 2
- 235000011118 potassium hydroxide Nutrition 0.000 claims description 2
- 235000007715 potassium iodide Nutrition 0.000 claims description 2
- 239000004302 potassium sorbate Substances 0.000 claims description 2
- 235000010241 potassium sorbate Nutrition 0.000 claims description 2
- 229940069338 potassium sorbate Drugs 0.000 claims description 2
- 235000019260 propionic acid Nutrition 0.000 claims description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 2
- 239000000741 silica gel Substances 0.000 claims description 2
- 229910002027 silica gel Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 229940083542 sodium Drugs 0.000 claims description 2
- 235000015424 sodium Nutrition 0.000 claims description 2
- 229960001462 sodium cyclamate Drugs 0.000 claims description 2
- 239000011775 sodium fluoride Substances 0.000 claims description 2
- 235000013024 sodium fluoride Nutrition 0.000 claims description 2
- 235000009518 sodium iodide Nutrition 0.000 claims description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 2
- 235000011152 sodium sulphate Nutrition 0.000 claims description 2
- 239000004334 sorbic acid Substances 0.000 claims description 2
- 235000010199 sorbic acid Nutrition 0.000 claims description 2
- 229940075582 sorbic acid Drugs 0.000 claims description 2
- 229960002920 sorbitol Drugs 0.000 claims description 2
- 235000019408 sucralose Nutrition 0.000 claims description 2
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 claims description 2
- 150000003866 tertiary ammonium salts Chemical class 0.000 claims description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 2
- 238000005550 wet granulation Methods 0.000 claims description 2
- 239000000811 xylitol Substances 0.000 claims description 2
- 235000010447 xylitol Nutrition 0.000 claims description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 2
- 229960002675 xylitol Drugs 0.000 claims description 2
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 claims 2
- 229940079593 drug Drugs 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- ZADYMNAVLSWLEQ-UHFFFAOYSA-N magnesium;oxygen(2-);silicon(4+) Chemical compound [O-2].[O-2].[O-2].[Mg+2].[Si+4] ZADYMNAVLSWLEQ-UHFFFAOYSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 235000019658 bitter taste Nutrition 0.000 description 4
- 239000004562 water dispersible granule Substances 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 3
- 239000007909 solid dosage form Substances 0.000 description 3
- 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 3
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 239000008119 colloidal silica Substances 0.000 description 2
- FSBVERYRVPGNGG-UHFFFAOYSA-N dimagnesium dioxido-bis[[oxido(oxo)silyl]oxy]silane hydrate Chemical compound O.[Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O FSBVERYRVPGNGG-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229910002016 Aerosil® 200 Inorganic materials 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000003781 beta lactamase inhibitor Substances 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 229940126813 beta-lactamase inhibitor Drugs 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000019793 magnesium trisilicate Nutrition 0.000 description 1
- 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
- 229940099273 magnesium trisilicate Drugs 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000008261 resistance mechanism Effects 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 239000004565 water dispersible tablet Substances 0.000 description 1
- 150000003952 β-lactams Chemical class 0.000 description 1
Classifications
-
- 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
- A61K31/542—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 heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
- A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/424—Oxazoles condensed with heterocyclic ring systems, e.g. clavulanic acid
-
- 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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- 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
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Definitions
- the present invention relates to pharmaceutical formulations comprising cefpodoxime proxetil.
- Cefpodoxime proxetil (figure I), chemical name of which is pivaloyloxymethyl 7-[2-(2- amino-thiazole-4-yl]-2-(syn)-methoxyimino-acetamido]-3-methoxymethyl-3-cefem-4- carboxylate, was first disclosed in the patent numbered EP0049118.
- Cefpodoxime proxetil is a third generation cephalosporin. Due to this feature, it is indicated in the treatment of infections caused by gram positive and gram negative bacteria.
- Clavulanic acid and derivatives thereof are known as the beta-lactamase inhibitors which withstand the beta-lactamase-originated resistance mechanism by suppressing the activity of beta-lactamase enzymes.
- Clavulanic acid and derivatives thereof can optionally be formulated as combined with antibiotics in order to increase efficiency of beta-lactam derivative antibiotics.
- Tablets which contain 100 mg and 200 mg of cefpodoxime are available on the market. When these tablets containing 100 or 200 mg of active agent are formulated with excipients, they become too large in size and this makes the use of this dosage form inconvenient for patients who have swallowing difficulties, especially for pediatric and geriatric patients.
- the molecule cefpodoxime proxetil has quite low water solubility; therefore bioavailability of tablet forms is rather low.
- the subject matter of the present invention relates to water dispersible formulations comprising cefpodoxime and optionally clavulanic acid or derivatives thereof which comprises a sweetener combination composed of an artificial sweetener, a disaccharide and a salt.
- a sweetener combination composed of an artificial sweetener, a disaccharide and a salt.
- pharmaceutical dosage forms in the form of water dispersible powder, tablet and/or granule can be taken by the patients more comfortably as they disperse in water homogeneously prior to use and their bioavailability is superior to said solid dosage forms; b) in addition, it has been observed that bitter taste of cefpodoxime is not perceived in the formulations formulated according to the present invention and therefore they can be used more comfortably by patients.
- Cefpodoxime that can be used in the water dispersible powder, tablet and/or granule formulations of the present invention can be in the form of its esters, solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms or free form and/or a combination thereof.
- cefpodoxime proxetil is preferably used.
- water dispersible powder, tablet and/or granule used in the text comprises single dose effervescent powder, tablets and/or granules; single dose water dispersible powders, tablets and granules; multiple dose powder, tablet and granules which are dispersed in water to form suspension; single dose water soluble powder, tablet and granules; multiple dose water soluble powder, tablet and granules. It is preferably in the form of multiple dose powder, tablet and granules which are dispersed in water to form suspension or single dose water dispersible powder, tablet or granules.
- one aspect of the present invention is water dispersible powder, tablet and/or granule formulations comprising cefpodoxime as the active agent and a sweetener combination comprised of an artificial sweetener, a disaccharide and a salt.
- another aspect of the present invention is water dispersible powder, tablet and/or granule formulations comprising cefpodoxime as the active agent and a sweetener combination comprised of an artificial sweetener, a disaccharide and a salt form, and additionally other pharmaceutically acceptable excipients.
- the water dispersible powder, tablet and/or granule formulation can comprise various excipients such as, but not limited to, binders, glidants, diluents, lubricants, humectants, disintegrants, basic agents, acidic agents, taste regulating agents, viscosity agents, flavoring agent, preservative agents and optionally effervescent couple.
- excipients such as, but not limited to, binders, glidants, diluents, lubricants, humectants, disintegrants, basic agents, acidic agents, taste regulating agents, viscosity agents, flavoring agent, preservative agents and optionally effervescent couple.
- the binder that can be used in the water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising ethyl cellulose, gelatine, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminum silicate, methyl cellulose, povidone or combinations thereof.
- the lubricant that can be used in the water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising calcium stearate, magnesium stearate, polyethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, talc, sodium benzoate.
- talc is preferably used as lubricant.
- the glidant that can be used in the water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising magnesium silicate, silicon dioxide, starch, talc, tribasic calcium phosphate or combinations thereof.
- silicon dioxide is used as glidant in the formulation of the present invention.
- the humectant that can be used in the water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising anhydrous sodium sulphate, silica gel and potassium carbonate or a combination thereof.
- the disintegrant that can be used in water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising carboxymethyl cellulose calcium, carboxymethyl cellulose sodium, microcrystalline cellulose, silicon dioxide, croscarmellose sodium, crospovidone, hydroxypropyl cellulose, methyl cellulose, povidone, magnesium aluminum silicate and starch or combinations thereof.
- the diluent that can be used in water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising calcium carbonate, calcium sulphate, dibasic calcium phosphate, tribasic calcium phosphate, calcium phosphate, calcium sulphate, microcrystalline cellulose, lactose, magnesium carbonate, magnesium oxide, maltodextrin, maltose, mannitol, sodium chloride, sorbitol, starch, xylitol or combinations thereof.
- the basic agent that can be used in the water dispersible powder, tablet and/or granule formulation of the present invention can be selected from a group comprising potassium carbonate, potassium bicarbonate, potassium citrate, potassium hydroxide, sodium carbonate, sodium bicarbonate or combinations thereof.
- the acidic agent that can be used in the water dispersible powder, tablet and/or granule formulation of the present invention can be selected from a group comprising acetic acid, citric acid, lactic acid, malic acid, phosphoric acid, propionic acid, tartaric acid or combinations thereof.
- citric acid is used in the formulation of the present invention as acidic agent.
- the taste regulating agent that can be used in water dispersible powder, tablet and/or granule formulation of the present invention can be selected from a group comprising artificial sweeteners such as acesulfame, aspartame, saccharine, saccharine sodium, lactitol, maltitol, sorbitol, sodium cyclamate, sucralose; a group comprising disaccharides such as sucrose, maltose, lactose; and a group comprising salts such as sodium chloride, potassium iodide, sodium iodide, sodium fluoride, potassium fluoride, potassium chloride.
- artificial sweeteners such as acesulfame, aspartame, saccharine, saccharine sodium, lactitol, maltitol, sorbitol, sodium cyclamate, sucralose
- disaccharides such as sucrose, maltose, lactose
- salts such as sodium chloride, potassium iodide,
- the ratio of disaccharide: artificial sugar: salt used in the formulation of the present invention is in the range of 15:5:1 to 5:1 :1, preferably in the range of 14:4:1 to 6:1:1, more preferably in the range of 13:3:1 to 7:1 :1.
- another aspect of the present invention is water dispersible formulations of cefpodoxime in which the ratio of disaccharide: artificial sugar: salt is in the range of 15:5:1 to 5:1:1.
- the sweetener combination for use in the formulation of the present invention preferably comprises aspartame as artificial sugar; sucrose as disaccharide; and sodium chloride as salt.
- the viscosity agent that can be used in water dispersible powder, tablet and/or granule formulation of the present invention can be selected from a group comprising carboxy methyl cellulose sodium, carboxy methyl cellulose calcium, colloidal silicone dioxide, ethyl cellulose, hydroxyl ethyl cellulose, hydroxypropyl cellulose, hydroxyl methyl cellulose, hypromellose or a combination thereof.
- the preservative agent that can be used in water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising methylparaben, ethylparaben, butylparaben, sorbic acid, tertiary ammonium salts, potassium sorbate, benzoic acid and/or salts thereof (sodium benzoate) and benzyl alcohol or a combination thereof.
- the effervescent couple that can optionally be used in water dispersible powder, tablet and granule formulation of the present invention can be selected from organic acids such as citric acid, tartaric acid, malic acid, fumaric acid etc. and basic agents such as sodium hydrogen carbonate, sodium carbonate, potassium carbonate and potassium hydrogen carbonate etc.
- the water dispersible powder, tablet and granule formulation of the present invention can comprise cefpodoxime in the range of 20-800 mg or its pharmaceutically acceptable esters, salts, hydrates, solvates or a combination thereof in an equal amount.
- the water dispersible powder, tablet and granule formulation of the present invention can comprise 5-60% of cefpodoxime or its pharmaceutically acceptable esters, solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms in proportion to total weight of unit dose.
- the water dispersible powder, tablet and granule formulation of the present invention can comprise 5-60 % of cefpodoxime and at least one; binder in the range of 0-40%; glidant in the range of 0.5-5%; lubricant in the range of 1-10%; humectant in the range of 0-40%; disintegrant and/or disintegrants in the range of 0-20%; diluent in the range of 0.5-60%; basic agent in the range of 0-40%; acidic agent in the range of 0.1-40%; taste regulating agent in the range of 1-25%; viscosity agent in the range of 2-15%; flavoring agent in the range of 0.1-5%; preservative agent in the range of 0-5% and optionally effervescent couple in the range of 0- 85% in proportion to the total weight of unit dose amount.
- the formulation of the present invention can be used for pharmaceutical compositions comprising clavulanic acid or derivatives thereof along with cefpodoxime.
- the present invention relates to pharmaceutical compositions comprising cefpodoxime and clavulanic acid or derivatives thereof; the sweetener combination comprised of an artificial sweetener, a disaccharide and a salt; and optionally pharmaceutically acceptable excipients in addition to these.
- Clavulanic acid that can optionally be used in the pharmaceutical composition of the present invention can be in the form of solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms or in free form and/or a combination thereof.
- potassium clavulanate is used in the present invention.
- the pharmaceutical composition of the present invention can comprise clavulanic acid in the range of 50-500 mg or its pharmaceutically acceptable salts, hydrates, solvates or a combination thereof in an equal amount.
- Clavulanic acid and its derivatives are extremely susceptible to moisture.
- potassium clavulanate in the pharmaceutical composition of the present invention is preferably used with a humectant in the ratio of 1 : 1.
- colloidal silica for instance colloidal silica anhydrous, for example Aerosil® 200, magnesium trisilicate, cellulose powder, Cabosil®, magnesium oxide, calcium silicate, Syloid®, starch, microcrystalline cellulose, talc can be used as the humectant.
- potassium clavulanate is preferably used with syloid in the ratio of 1 : 1.
- the pharmaceutical composition of the present invention can comprise 5-50% of clavulanic acid in proportion to total weight of unit dose amount or pharmaceutically acceptable salts, hydrates, solvates or combinations thereof in an equal amount.
- the present invention relates to processes that can be used for preparation of water dispersible powder, tablet and/or granule formulations comprising pharmaceutically acceptable excipients in addition to cefpodoxime as active agent.
- the process of the present invention comprises granulation of the active agent cefpodoxime proxetil by conventional wet and/or dry granulation methods; or powdering cefpodoxime proxetil and other excipients by mixing them by dry blending method and optionally compressing the mixture in tablet form.
- the powder, tablet and/or granules obtained are dispersed in water before use by patients and taken in liquid form.
- Another aspect of the present invention is that the formulation prepared according to said invention is used in the treatment of diseases related with infections caused by gram negative and gram positive bacteria.
- Water dispersible tablets of the present invention can be prepared as specified below, yet the invention is not restricted to these examples.
- EXAMPLE 1 Formulation and process for preparation of water dispersible granule
- a method for preparation of water dispersible granule given in this example comprises, but not limited to, dissolving cefpodoxime proxetil in a suitable solvent; and granulating the diluent with this solution; and drying and then mixing the granules obtained with the other excipients.
- a method for preparation of water dispersible granule given in this example comprises, but not limited to, dissolving cefpodoxime proxetil in a suitable solvent; and granulating the diluent with this solution; and drying and then mixing the granules obtained with the potassium clavylanate-syloid (1 :1) and the other excipients.
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to pharmaceutical formulations comprising cefpodoxime proxetil.
Description
CEFPODOXIME PROXETIL FORMULATIONS COMPRISING TASTE
REGULATING AGENT
The present invention relates to pharmaceutical formulations comprising cefpodoxime proxetil.
Background of the Invention:
Cefpodoxime proxetil (figure I), chemical name of which is pivaloyloxymethyl 7-[2-(2- amino-thiazole-4-yl]-2-(syn)-methoxyimino-acetamido]-3-methoxymethyl-3-cefem-4- carboxylate, was first disclosed in the patent numbered EP0049118.
Figure 1
Cefpodoxime proxetil is a third generation cephalosporin. Due to this feature, it is indicated in the treatment of infections caused by gram positive and gram negative bacteria.
Clavulanic acid and derivatives thereof (for instance its salts such as potassium clavulanate) are known as the beta-lactamase inhibitors which withstand the beta-lactamase-originated resistance mechanism by suppressing the activity of beta-lactamase enzymes. Clavulanic acid and derivatives thereof can optionally be formulated as combined with antibiotics in order to increase efficiency of beta-lactam derivative antibiotics.
Tablets which contain 100 mg and 200 mg of cefpodoxime are available on the market. When these tablets containing 100 or 200 mg of active agent are formulated with excipients, they become too large in size and this makes the use of this dosage form inconvenient for patients who have swallowing difficulties, especially for pediatric and geriatric patients.
The molecule cefpodoxime proxetil has quite low water solubility; therefore bioavailability of tablet forms is rather low.
Water dispersible dosage forms have been developed in order to overcome problems that solid dosage forms pose. However, the fact that cefpodoxime has a quite bitter taste poses difficulties in developing formulations having pleasant taste which can be taken by patient without feeling uncomfortable.
In the current situation, there is need for water dispersible formulations which comprise cefpodoxime, bitter taste of which is masked, and optionally clavulanic acid or its derivatives; have higher bioavailability than solid dosage forms in order to meet the needs of patients requiring special consideration for instance pediatric and geriatric patients.
Description of the invention:
The subject matter of the present invention relates to water dispersible formulations comprising cefpodoxime and optionally clavulanic acid or derivatives thereof which comprises a sweetener combination composed of an artificial sweetener, a disaccharide and a salt. Surprisingly, it has been found that water dispersible powder, tablet and/or granules comprising cefpodoxime as the active agent and a sweetener combination comprised of an artificial sweetener, a disaccharide and a salt constitute a formulation in which the bitter taste of cefpodoxime is not perceived.
According to this, pharmaceutical dosage forms in the form of water dispersible powder, tablet and/or granule; a) can be taken by the patients more comfortably as they disperse in water homogeneously prior to use and their bioavailability is superior to said solid dosage forms; b) in addition, it has been observed that bitter taste of cefpodoxime is not perceived in the formulations formulated according to the present invention and therefore they can be used more comfortably by patients.
Cefpodoxime that can be used in the water dispersible powder, tablet and/or granule formulations of the present invention can be in the form of its esters, solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous
forms or free form and/or a combination thereof. In the present invention, cefpodoxime proxetil is preferably used.
The term "water dispersible powder, tablet and/or granule" used in the text comprises single dose effervescent powder, tablets and/or granules; single dose water dispersible powders, tablets and granules; multiple dose powder, tablet and granules which are dispersed in water to form suspension; single dose water soluble powder, tablet and granules; multiple dose water soluble powder, tablet and granules. It is preferably in the form of multiple dose powder, tablet and granules which are dispersed in water to form suspension or single dose water dispersible powder, tablet or granules.
According to this, one aspect of the present invention is water dispersible powder, tablet and/or granule formulations comprising cefpodoxime as the active agent and a sweetener combination comprised of an artificial sweetener, a disaccharide and a salt.
According to this, another aspect of the present invention is water dispersible powder, tablet and/or granule formulations comprising cefpodoxime as the active agent and a sweetener combination comprised of an artificial sweetener, a disaccharide and a salt form, and additionally other pharmaceutically acceptable excipients.
In addition to cefpodoxime and the sweetener combination; the water dispersible powder, tablet and/or granule formulation can comprise various excipients such as, but not limited to, binders, glidants, diluents, lubricants, humectants, disintegrants, basic agents, acidic agents, taste regulating agents, viscosity agents, flavoring agent, preservative agents and optionally effervescent couple.
The binder that can be used in the water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising ethyl cellulose, gelatine, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminum silicate, methyl cellulose, povidone or combinations thereof.
The lubricant that can be used in the water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising calcium stearate, magnesium stearate, polyethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, talc, sodium benzoate. In the formulation of the present invention, talc is preferably used as lubricant.
The glidant that can be used in the water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising magnesium silicate, silicon dioxide, starch, talc, tribasic calcium phosphate or combinations thereof. Preferably, silicon dioxide is used as glidant in the formulation of the present invention.
The humectant that can be used in the water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising anhydrous sodium sulphate, silica gel and potassium carbonate or a combination thereof.
The disintegrant that can be used in water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising carboxymethyl cellulose calcium, carboxymethyl cellulose sodium, microcrystalline cellulose, silicon dioxide, croscarmellose sodium, crospovidone, hydroxypropyl cellulose, methyl cellulose, povidone, magnesium aluminum silicate and starch or combinations thereof.
The diluent that can be used in water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising calcium carbonate, calcium sulphate, dibasic calcium phosphate, tribasic calcium phosphate, calcium phosphate, calcium sulphate, microcrystalline cellulose, lactose, magnesium carbonate, magnesium oxide, maltodextrin, maltose, mannitol, sodium chloride, sorbitol, starch, xylitol or combinations thereof.
The basic agent that can be used in the water dispersible powder, tablet and/or granule formulation of the present invention can be selected from a group comprising potassium carbonate, potassium bicarbonate, potassium citrate, potassium hydroxide, sodium carbonate, sodium bicarbonate or combinations thereof.
The acidic agent that can be used in the water dispersible powder, tablet and/or granule formulation of the present invention can be selected from a group comprising acetic acid, citric acid, lactic acid, malic acid, phosphoric acid, propionic acid, tartaric acid or combinations thereof. Preferably, citric acid is used in the formulation of the present invention as acidic agent.
The taste regulating agent that can be used in water dispersible powder, tablet and/or granule formulation of the present invention can be selected from a group comprising artificial sweeteners such as acesulfame, aspartame, saccharine, saccharine sodium, lactitol, maltitol, sorbitol, sodium cyclamate, sucralose; a group comprising disaccharides such as sucrose,
maltose, lactose; and a group comprising salts such as sodium chloride, potassium iodide, sodium iodide, sodium fluoride, potassium fluoride, potassium chloride.
The ratio of disaccharide: artificial sugar: salt used in the formulation of the present invention is in the range of 15:5:1 to 5:1 :1, preferably in the range of 14:4:1 to 6:1:1, more preferably in the range of 13:3:1 to 7:1 :1.
According to this, another aspect of the present invention is water dispersible formulations of cefpodoxime in which the ratio of disaccharide: artificial sugar: salt is in the range of 15:5:1 to 5:1:1.
The sweetener combination for use in the formulation of the present invention preferably comprises aspartame as artificial sugar; sucrose as disaccharide; and sodium chloride as salt.
The viscosity agent that can be used in water dispersible powder, tablet and/or granule formulation of the present invention can be selected from a group comprising carboxy methyl cellulose sodium, carboxy methyl cellulose calcium, colloidal silicone dioxide, ethyl cellulose, hydroxyl ethyl cellulose, hydroxypropyl cellulose, hydroxyl methyl cellulose, hypromellose or a combination thereof.
The preservative agent that can be used in water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising methylparaben, ethylparaben, butylparaben, sorbic acid, tertiary ammonium salts, potassium sorbate, benzoic acid and/or salts thereof (sodium benzoate) and benzyl alcohol or a combination thereof.
The effervescent couple that can optionally be used in water dispersible powder, tablet and granule formulation of the present invention can be selected from organic acids such as citric acid, tartaric acid, malic acid, fumaric acid etc. and basic agents such as sodium hydrogen carbonate, sodium carbonate, potassium carbonate and potassium hydrogen carbonate etc.
The water dispersible powder, tablet and granule formulation of the present invention can comprise cefpodoxime in the range of 20-800 mg or its pharmaceutically acceptable esters, salts, hydrates, solvates or a combination thereof in an equal amount.
The water dispersible powder, tablet and granule formulation of the present invention can comprise 5-60% of cefpodoxime or its pharmaceutically acceptable esters, solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms in proportion to total weight of unit dose.
The water dispersible powder, tablet and granule formulation of the present invention can comprise 5-60 % of cefpodoxime and at least one; binder in the range of 0-40%; glidant in the range of 0.5-5%; lubricant in the range of 1-10%; humectant in the range of 0-40%; disintegrant and/or disintegrants in the range of 0-20%; diluent in the range of 0.5-60%; basic agent in the range of 0-40%; acidic agent in the range of 0.1-40%; taste regulating agent in the range of 1-25%; viscosity agent in the range of 2-15%; flavoring agent in the range of 0.1-5%; preservative agent in the range of 0-5% and optionally effervescent couple in the range of 0- 85% in proportion to the total weight of unit dose amount.
If required, the formulation of the present invention can be used for pharmaceutical compositions comprising clavulanic acid or derivatives thereof along with cefpodoxime.
According to this, the present invention relates to pharmaceutical compositions comprising cefpodoxime and clavulanic acid or derivatives thereof; the sweetener combination comprised of an artificial sweetener, a disaccharide and a salt; and optionally pharmaceutically acceptable excipients in addition to these.
Clavulanic acid that can optionally be used in the pharmaceutical composition of the present invention can be in the form of solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms or in free form and/or a combination thereof. Preferably, potassium clavulanate is used in the present invention.
The pharmaceutical composition of the present invention can comprise clavulanic acid in the range of 50-500 mg or its pharmaceutically acceptable salts, hydrates, solvates or a combination thereof in an equal amount.
Clavulanic acid and its derivatives (e.g. potassium clavulanate) are extremely susceptible to moisture. To this respect, potassium clavulanate in the pharmaceutical composition of the present invention is preferably used with a humectant in the ratio of 1 : 1.
One or more of the substances comprising silica; colloidal silica, for instance colloidal silica anhydrous, for example Aerosil® 200, magnesium trisilicate, cellulose powder, Cabosil®, magnesium oxide, calcium silicate, Syloid®, starch, microcrystalline cellulose, talc can be used as the humectant.
In the pharmaceutical composition of the present invention, potassium clavulanate is preferably used with syloid in the ratio of 1 : 1.
The pharmaceutical composition of the present invention can comprise 5-50% of clavulanic acid in proportion to total weight of unit dose amount or pharmaceutically acceptable salts, hydrates, solvates or combinations thereof in an equal amount.
In another aspect, the present invention relates to processes that can be used for preparation of water dispersible powder, tablet and/or granule formulations comprising pharmaceutically acceptable excipients in addition to cefpodoxime as active agent.
According to this, the process of the present invention comprises granulation of the active agent cefpodoxime proxetil by conventional wet and/or dry granulation methods; or powdering cefpodoxime proxetil and other excipients by mixing them by dry blending method and optionally compressing the mixture in tablet form.
The powder, tablet and/or granules obtained are dispersed in water before use by patients and taken in liquid form.
Another aspect of the present invention is that the formulation prepared according to said invention is used in the treatment of diseases related with infections caused by gram negative and gram positive bacteria.
Water dispersible tablets of the present invention can be prepared as specified below, yet the invention is not restricted to these examples.
EXAMPLE 1: Formulation and process for preparation of water dispersible granule
A method for preparation of water dispersible granule given in this example comprises, but not limited to, dissolving cefpodoxime proxetil in a suitable solvent; and granulating the
diluent with this solution; and drying and then mixing the granules obtained with the other excipients.
EXAMPLE 2: Formulation and process for preparation of water dispersible granule
A method for preparation of water dispersible granule given in this example comprises, but not limited to, dissolving cefpodoxime proxetil in a suitable solvent; and granulating the diluent with this solution; and drying and then mixing the granules obtained with the potassium clavylanate-syloid (1 :1) and the other excipients.
Claims
1. A pharmaceutical composition comprising cefpodoxime characterized in that said composition is water dispersible cefpodoxime formulation comprising a sweetener combination composed of an artificial sweetener, a disaccharide and a salt.
2. The pharmaceutical composition according to claim 1, wherein cefpodoxime that is used as active agent can be in the form of its esters, solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms or in free form and/or a combination thereof.
3. The pharmaceutical composition according to claim 2, wherein cefpodoxime proxetil is used as the active agent.
4. The pharmaceutical composition according to claim 1 , wherein said composition can be in the form of water dispersible powder, tablet and/or granules; single dose effervescent powder, tablets and/or granules; single dose water dispersible powders, tablets and/or granules; multiple dose powder, tablet and/or granules which are dispersed in water to form suspension; single dose water soluble powder, tablet and/or granules; multiple dose water soluble powder, tablet and/or granules.
5. The pharmaceutical composition according to claim 1, wherein said composition comprises pharmaceutically acceptable excipients in addition to cefpodoxime used as the active agent and a sweetener combination composed of an artificial sweetener, a disaccharide and a salt.
6. The pharmaceutical composition according to claim 5, wherein said composition can comprise binder, glidant, lubricant, humectant, disintegrant, diluent, basic agent, acidic agent, sweetener, viscosity agent, flavoring agent, preservative agent and/or effervescent couple in addition to cefpodoxime as the active agent and a sweetener combination composed of an artificial sweetener, a disaccharide and a salt.
7. The pharmaceutical composition according to claim 6, wherein the binder can be selected from a group comprising ethyl cellulose, gelatine, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminum silicate, methyl cellulose, povidone or a combination thereof.
8. The pharmaceutical composition according to claim 6, wherein the lubricant can be selected from a group comprising calcium stearate, magnesium stearate, polyethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, talc, sodium benzoate or a combination thereof.
9. The pharmaceutical composition according to claim 8, wherein talc is preferably used as lubricant.
10. The pharmaceutical composition according to claim 6, wherein the glidant can be selected from a group comprising magnesium silicate, silicon dioxide, starch, talc, tribasic calcium phosphate or combinations thereof.
11. The pharmaceutical composition according to claim 10, wherein silicon dioxide is preferably used as glidant.
12. The pharmaceutical composition according to claim 6, wherein the humectant can be selected from a group comprising anhydrous sodium sulphate, silica gel and potassium carbonate or a combination thereof.
13. The pharmaceutical composition according to claim 6, wherein the disintegrant can be selected from a group comprising carboxymethyl cellulose calcium, carboxymethylcellulose sodium, microcrystalline cellulose, silicon dioxide, croscarmellose sodium, crospovidone, hydroxypropyl cellulose, methyl cellulose, povidone, magnesium aluminum silicate, starch or combinations thereof.
14. The pharmaceutical composition according to claim 6, wherein the diluent can be selected from a group comprising calcium carbonate, calcium sulphate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulphate, microcrystalline cellulose, lactose, magnesium carbonate, magnesium oxide, maltodextrin, maltose, mannitol, sodium chloride, sorbitol, starch, xylitol or combinations thereof.
15. The pharmaceutical composition according to claim 6, wherein the basic agent can be selected from a group comprising potassium carbonate, potassium bicarbonate, potassium citrate, potassium hydroxide, sodium carbonate, sodium bicarbonate or combinations thereof.
16. The pharmaceutical composition according to claim 6, wherein the acidic agent can be selected from a group comprising acetic acid, citric acid, lactic acid, malic acid, phosphoric acid, propionic acid, tartaric acid or combinations thereof.
17. The pharmaceutical composition according to claim 16, wherein citric acid is preferably used as acidic agent.
18. The pharmaceutical composition according to claim 6, wherein the taste regulating agent can be selected from a group comprising artificial sweeteners such as acesulfame, aspartame, saccharine, saccharine sodium, lactitol, maltitol, sorbitol, sodium cyclamate, sucralose; a group comprising disaccharides such as sucrose, maltose, lactose; and a group comprising salts such as sodium chloride, potassium iodide, sodium iodide, sodium fluoride, potassium fluoride, potassium chloride.
19. The pharmaceutical composition according to claim 18, wherein the ratio of disaccharide: artificial sugar: salt in the taste regulating agent combination is in the range of 15:5:1 to 5:1:1.
20. The pharmaceutical composition according to claim 19, wherein the ratio of disaccharide: artificial sugar: salt in the taste regulating agent combination is in the range of 14:4:1 to 6:1:1.
21. The pharmaceutical composition according to claim 20, wherein the ratio of disaccharide: artificial sugar: salt in the taste regulating agent combination is in the range of 13:3:1 to7:l:l.
22. The pharmaceutical composition according to claim 18, wherein the taste regulating agent comprises aspartame as artificial sugar; sucrose as disaccharide; and sodium chloride as salt.
23. The pharmaceutical composition according to claim 6, wherein the viscosity agent can be selected from a group comprising carboxy methyl cellulose sodium, carboxy methyl cellulose calcium, colloidal silicone dioxide, ethyl cellulose, hydroxyl ethyl cellulose, hydroxypropyl cellulose, hydroxyl methyl cellulose, hypromellose or a combination thereof.
24. The pharmaceutical composition according to claim 6, wherein the preservative agent can be selected from a group comprising methylparaben, ethylparaben, butylparaben, sorbic acid, tertiary ammonium salts, potassium sorbate, benzoic acid and/or salts thereof (sodium benzoate) and benzyl alcohol or a combination thereof.
25. The pharmaceutical composition according to claim 6, wherein the effervescent couple can be selected from organic acids such as citric acid, tartaric acid, malic acid, fumaric acid etc. and basic agents such as sodium hydrogen carbonate, sodium carbonate, potassium carbonate and potassium hydrogen carbonate etc.
26. The pharmaceutical composition according to claim 1, wherein said composition can comprise cefpodoxime in the range of 20-800 mg or its pharmaceutically acceptable esters, salts, hydrates, solvates or a combination thereof in an equal amount.
27. The pharmaceutical composition according to claim 1, wherein said composition can comprise 5-60% of cefpodoxime or its pharmaceutically acceptable esters, solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms in proportion to total amount of unit dose.
28. The pharmaceutical composition according to claim 1, wherein said composition can comprise 5-60 % of cefpodoxime; binder in the range of 0-40%; glidant in the range of 0.5-5%; lubricant in the range of 1-10%; humectant in the range of 0-40%; disintegrant and/or disintegrants in the range of 0-20%; diluent in the range of 0.5- 60%; basic agent in the range of 0-40%; acidic agent in the range of 0.1-40%; taste regulating agent in the range of 1-25%; viscosity agent in the range of 2-15%; flavoring agent in the range of 0.1-5%; preservative agent in the range of 0-5% and optionally effervescent couple in the range of 0-85% in proportion to the total weight of unit dose amount.
29. The pharmaceutical composition according to any preceding claims, wherein said composition comprises clavulanic acid or derivatives thereof in addition to cefpodoxime it comprises as active agent.
30. The pharmaceutical composition according to claim 29, wherein clavulanic acid can be in the form of its solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms or in free form and/or a combination thereof.
31. The pharmaceutical composition according to claim 30, wherein potassium clavulanate is used in said composition.
32. A method for preparation of the pharmaceutical composition as claimed in any of the claims above, wherein said method comprises granulation of the active agent cefpodoxime proxetil by conventional wet and/or dry granulation methods; or powdering cefpodoxime proxetil and other excipients after mixing them by dry blending method and optionally compressing tablets.
33. The pharmaceutical composition according to claim 1, wherein said composition is used in production of a drug prepared so as to be used in the treatment of diseases related with infections caused by gram negative and gram positive bacteria.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11767093.5A EP2663289A2 (en) | 2010-08-25 | 2011-08-24 | Cefpodoxime proxetil formulations comprising taste regulating agent |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2010/07107A TR201007107A1 (en) | 2010-08-25 | 2010-08-25 | Formulations of cefpodoxime proxetil containing taste regulating agent. |
| TR2010/07107 | 2010-08-25 |
Publications (2)
| Publication Number | Publication Date |
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| WO2012026908A2 true WO2012026908A2 (en) | 2012-03-01 |
| WO2012026908A3 WO2012026908A3 (en) | 2012-09-07 |
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| Application Number | Title | Priority Date | Filing Date |
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| PCT/TR2011/000201 WO2012026908A2 (en) | 2010-08-25 | 2011-08-24 | Cefpodoxime proxetil formulations comprising taste regulating agent |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP2663289A2 (en) |
| TR (1) | TR201007107A1 (en) |
| WO (1) | WO2012026908A2 (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0049118A2 (en) | 1980-09-30 | 1982-04-07 | Sankyo Company Limited | Cephalosporin derivatives, their preparation and compositions containing them |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004522782A (en) * | 2001-02-27 | 2004-07-29 | ランバクシー ラボラトリーズ リミテッド | Oral pharmaceutical composition of cefpodoxime proxetil |
| TW200404550A (en) * | 2002-07-08 | 2004-04-01 | Sankyo Co | Cepharospolin formulation for oral use |
| KR20050062514A (en) * | 2002-07-16 | 2005-06-23 | 랜박시 래보러터리스 리미티드 | Dispersible tablets for oral administration |
| JP2008540403A (en) * | 2005-05-05 | 2008-11-20 | ルピン・リミテッド | Stabilized oral pharmaceutical composition of cephalosporin |
| TR201002878A2 (en) * | 2010-04-13 | 2011-10-21 | Bi̇lgi̇ç Mahmut | Pharmaceutical compositions comprising cefpodoxime proxetil. |
-
2010
- 2010-08-25 TR TR2010/07107A patent/TR201007107A1/en unknown
-
2011
- 2011-08-24 EP EP11767093.5A patent/EP2663289A2/en not_active Withdrawn
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0049118A2 (en) | 1980-09-30 | 1982-04-07 | Sankyo Company Limited | Cephalosporin derivatives, their preparation and compositions containing them |
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| EP2663289A2 (en) | 2013-11-20 |
| WO2012026908A3 (en) | 2012-09-07 |
| TR201007107A1 (en) | 2012-03-21 |
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