EP2575777A1 - Formulation comprising cefpodoxime proxetil and clavulanic acid - Google Patents
Formulation comprising cefpodoxime proxetil and clavulanic acidInfo
- Publication number
- EP2575777A1 EP2575777A1 EP11770579.8A EP11770579A EP2575777A1 EP 2575777 A1 EP2575777 A1 EP 2575777A1 EP 11770579 A EP11770579 A EP 11770579A EP 2575777 A1 EP2575777 A1 EP 2575777A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- pharmaceutical composition
- composition according
- clavulanic acid
- microcrystalline cellulose
- cefpodoxime proxetil
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 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 35
- 229960004797 cefpodoxime proxetil Drugs 0.000 title claims abstract description 35
- 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 title claims abstract description 32
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 229960003324 clavulanic acid Drugs 0.000 title claims abstract description 29
- 239000000203 mixture Substances 0.000 title claims description 30
- 238000009472 formulation Methods 0.000 title claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 59
- 239000013543 active substance Substances 0.000 claims abstract description 6
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 21
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 21
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 21
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 20
- 239000007884 disintegrant Substances 0.000 claims description 15
- 150000004677 hydrates Chemical class 0.000 claims description 12
- 239000012453 solvate Substances 0.000 claims description 12
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 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 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 9
- 239000000314 lubricant Substances 0.000 claims description 9
- 239000003826 tablet Substances 0.000 claims description 9
- 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 8
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 8
- 239000011248 coating agent Substances 0.000 claims description 8
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 8
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 8
- 239000004094 surface-active agent Substances 0.000 claims description 8
- 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 7
- 229920002472 Starch Polymers 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- 239000002245 particle Substances 0.000 claims description 6
- 239000008107 starch Substances 0.000 claims description 6
- 235000019698 starch Nutrition 0.000 claims description 6
- 239000000454 talc Substances 0.000 claims description 6
- 235000012222 talc Nutrition 0.000 claims description 6
- 229910052623 talc Inorganic materials 0.000 claims description 6
- 235000010980 cellulose Nutrition 0.000 claims description 5
- 229920002678 cellulose Polymers 0.000 claims description 5
- 239000001913 cellulose Substances 0.000 claims description 5
- -1 glidant Substances 0.000 claims description 5
- 239000003906 humectant Substances 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- 235000011132 calcium sulphate Nutrition 0.000 claims description 4
- 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 claims description 4
- 239000000395 magnesium oxide Substances 0.000 claims description 4
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 4
- 235000012245 magnesium oxide Nutrition 0.000 claims description 4
- 239000000391 magnesium silicate Substances 0.000 claims description 4
- 235000019359 magnesium stearate Nutrition 0.000 claims description 4
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims description 4
- 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 description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 235000019731 tricalcium phosphate Nutrition 0.000 claims description 4
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 239000000377 silicon dioxide Substances 0.000 claims description 3
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 3
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 claims description 2
- 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 2
- 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 2
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 claims description 2
- 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 2
- 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 2
- 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 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 239000005913 Maltodextrin Substances 0.000 claims description 2
- 229920002774 Maltodextrin Polymers 0.000 claims description 2
- 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 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- 239000008118 PEG 6000 Substances 0.000 claims description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 2
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 claims description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 2
- 235000010216 calcium carbonate Nutrition 0.000 claims description 2
- XAAHAAMILDNBPS-UHFFFAOYSA-L calcium hydrogenphosphate dihydrate Chemical compound O.O.[Ca+2].OP([O-])([O-])=O XAAHAAMILDNBPS-UHFFFAOYSA-L 0.000 claims description 2
- 239000000378 calcium silicate Substances 0.000 claims description 2
- 235000012241 calcium silicate Nutrition 0.000 claims description 2
- 229910052918 calcium silicate Inorganic materials 0.000 claims description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 2
- 235000013539 calcium stearate Nutrition 0.000 claims description 2
- 239000008116 calcium stearate Substances 0.000 claims description 2
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 claims description 2
- 229960002798 cetrimide Drugs 0.000 claims description 2
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 2
- 229940095079 dicalcium phosphate anhydrous Drugs 0.000 claims description 2
- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 claims description 2
- 229960000878 docusate sodium Drugs 0.000 claims description 2
- 238000007908 dry granulation Methods 0.000 claims description 2
- 239000007941 film coated tablet Substances 0.000 claims description 2
- 238000000227 grinding Methods 0.000 claims description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 2
- 239000008101 lactose Substances 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
- 235000019793 magnesium trisilicate Nutrition 0.000 claims description 2
- 229910000386 magnesium trisilicate Inorganic materials 0.000 claims description 2
- 229940099273 magnesium trisilicate 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
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 2
- 235000019422 polyvinyl alcohol Nutrition 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
- 229940103091 potassium benzoate Drugs 0.000 claims description 2
- 235000010235 potassium benzoate Nutrition 0.000 claims description 2
- 239000004300 potassium benzoate Substances 0.000 claims description 2
- 235000012239 silicon dioxide Nutrition 0.000 claims description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 2
- 235000010234 sodium benzoate Nutrition 0.000 claims description 2
- 239000004299 sodium benzoate Substances 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- 235000002639 sodium chloride Nutrition 0.000 claims description 2
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 claims description 2
- 239000000600 sorbitol Substances 0.000 claims description 2
- 235000010356 sorbitol Nutrition 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
- 229940075614 colloidal silicon dioxide Drugs 0.000 claims 1
- 238000004090 dissolution Methods 0.000 description 9
- 239000003781 beta lactamase inhibitor Substances 0.000 description 3
- 229940126813 beta-lactamase inhibitor Drugs 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 2
- 239000008119 colloidal silica Substances 0.000 description 2
- 229960005168 croscarmellose Drugs 0.000 description 2
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- 229910002016 Aerosil® 200 Inorganic materials 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 206010018612 Gonorrhoea Diseases 0.000 description 1
- 206010021531 Impetigo Diseases 0.000 description 1
- 206010024971 Lower respiratory tract infections Diseases 0.000 description 1
- 208000016604 Lyme disease Diseases 0.000 description 1
- 206010033078 Otitis media Diseases 0.000 description 1
- 201000007100 Pharyngitis Diseases 0.000 description 1
- 206010037596 Pyelonephritis Diseases 0.000 description 1
- 208000006311 Pyoderma Diseases 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 206010062255 Soft tissue infection Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 229940090805 clavulanate Drugs 0.000 description 1
- 201000003146 cystitis Diseases 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 208000001786 gonorrhea Diseases 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000008203 oral pharmaceutical composition Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000008261 resistance mechanism Effects 0.000 description 1
- 208000020029 respiratory tract infectious disease Diseases 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 201000009890 sinusitis Diseases 0.000 description 1
- 206010040872 skin infection Diseases 0.000 description 1
- 206010044008 tonsillitis Diseases 0.000 description 1
- 208000000143 urethritis Diseases 0.000 description 1
- 239000002132 β-lactam antibiotic Substances 0.000 description 1
- 229940124586 β-lactam antibiotics Drugs 0.000 description 1
- 229940126085 β‑Lactamase Inhibitor Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
- A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
Definitions
- the present invention relates to pharmaceutical compositions comprising cefpodoxime proxetil and clavulanic acid and/or derivatives thereof as the active agents.
- Cefpodoxime proxetil (Formula 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.
- Clavulanic acid is a beta-lactamase inhibitor illustrated in Formula 2.
- 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.
- EP0593573 comprises a formulation relating to suspension forms of beta-lactam antibiotics and beta lactamase inhibitors.
- suspension forms are not preferred much as they have the potential of high and/or uncontrolled dose intake; there appear problems in their physical and chemical stability; they have high manufacture costs and they cause problems in use and carrying.
- the inventors have aimed to develop stable oral pharmaceutical formulations which comprise cefpodoxime proxetil and clavulanic acid derivatives thereof together and eliminate the low solubility problem of cefpodoxime proxetil.
- the present invention relates to stable pharmaceutical compositions with good solubility characteristics in which cefpodoxime proxetil and clavulanic acid are formulated together. It has surprisingly been seen that when the pharmaceutical composition comprising cefpodoxime proxetil and clavulanic acid wherein
- each one of the cellulose-based disintegrants is present in an amount more than 7% by weight with respect to the weight of the unit dose is developed, dissolution of the cefpodoxime proxetil increases and dissolution time of the composition decreases.
- the first aspect of the present invention is the pharmaceutical compositions comprising cefpodoxime proxetil and clavulanic acid as the active agents wherein a combination of croscarmellose and microcrystalline cellulose is used as the disintegrant and each one of the cellulose-based disintegrants is present in an amount more than 7% with respect to the unit dose.
- Cefpodoxime proxetil that can be used in the pharmaceutical composition of the present invention can be in the form of its solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms or in free base form and/or a combination thereof.
- Clavulanic acid that can be used in the pharmaceutical composition of the present invention can be in the form of its solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms or free base form and/or a combination thereof.
- potassium clavulanate is used in the present invention.
- Croscarmellose sodium used in the pharmaceutical composition according to the present invention is present in an amount more than 7%, preferably in the range of 8-15%, more preferably in the range of 9-12% with respect to unit dose amount. Although the use of croscarmellose sodium in this specified amount is more than the amount disclosed in the prior art, the inventors have found that the dissolution rate of the composition increases in contrast to expectations.
- compositions comprising cefpodoxime proxetil and clavulanic acid or its derivatives wherein croscarmellose sodium is preferably used in an amount in the range of 8-15%, more preferably in an amount in the range of 9-12% by weight with respect to the weight of the unit dose.
- Microcrystalline cellulose used in the pharmaceutical composition according to the present invention is present in an amount more than 7%, preferably in the range of 8-15%, more preferably in the range of 9-13% with respect to unit dose amount.
- the inventors have found that the dissolution time reduces by 60% in the case that microcrystalline cellulose is used in said amount.
- compositions comprising cefpodoxime proxetil and clavulanic acid or its derivatives wherein microcrystalline cellulose is preferably used in an amount in the range of 8-15%, more preferably in an amount in the range of 9-13% by weight with respect to the weight of the unit dose.
- each cellulose-based disintegrant in an amount more than 7% with respect to the unit dose has an important effect on both the increase of dissolution of cefpodoxime proxetil and decrease in dissolution time of the composition comprising cefpodoxime proxetil and clavulanic acid.
- the inventors have observed that an optimum particle size of the cellulose-based disintegrant used in the composition of the present invention has a considerable effect on the disintegration and dissolution of the composition. They have found that when the particle size of microcrystalline cellulose used in the present invention is less than 100 ⁇ , preferably in the range of 30-90 ⁇ and more preferably in the range of 40-60 ⁇ , the dissolution of the composition increases and also dissolution time decreases.
- compositions comprising cefpodoxime proxetil and clavulanic acid or its derivatives wherein microcrystalline cellulose with a particle size less than 100 ⁇ , preferably in the range of 30- 90 ⁇ and more preferably in the range of 40-60 ⁇ is used in the disintegrant combination.
- the formulation of the present invention can comprise various excipients such as, but not limited to, glidants, lubricants, diluents, surfactants and optionally coating agents.
- the glidant that can be used in the pharmaceutical composition of the present invention can be selected from, but not limited to, a group comprising magnesium silicate, silicon dioxide, starch, talc, tribasic calcium phosphate or combinations thereof.
- the lubricant that can be used in the pharmaceutical composition of the present invention can be selected from, but not limited to, a group comprising calcium stearate, magnesium stearate, polyoxyethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, talc, sodium benzoate or combinations thereof.
- magnesium stearate is used as the lubricant in the pharmaceutical composition of the present invention.
- the diluent that can be used in the pharmaceutical composition of the present invention can be selected from, but not limited to, a group comprising calcium carbonate, calcium sulfate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, microcrystalline cellulose, lactose, magnesium carbonate, magnesium oxide, maltodextrin, maltose, mannitol, sodium chloride, sorbitol, starch, xylitol or combinations thereof.
- the surfactant that can be used in the pharmaceutical composition of the present invention can be selected from, but not limited to, a group comprising docusate sodium, sorbitan esters, cetrimide and sodium lauryl sulfate.
- sodium lauryl sulfate is preferably used as the surfactant.
- the pharmaceutical composition of the present invention can comprise 20-800 mg cefpodoxime proxetil or its pharmaceutically acceptable salts, hydrates, solvates or combinations thereof in an equal amount.
- the pharmaceutical composition of the present invention can comprise 50-500 mg clavulanic acid or its pharmaceutically acceptable salts, hydrates, solvates or combinations thereof in an equal amount.
- Clavulanic acid and its derivatives e.g. potassium clavulanate
- potassium clavulanate in the pharmaceutical composition 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 used with microcrystalline cellulose preferably in the ratio of 1 : 1.
- the pharmaceutical composition of the present invention can comprise 5-60% cefpodoxime proxetil in proportion to total weight of unit dose or pharmaceutically acceptable solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms thereof.
- the pharmaceutical composition of the present invention can comprise 5-50% clavulanic acid in proportion to total weight of unit dose or pharmaceutically acceptable salts, hydrates, solvates or combinations thereof in an equal amount.
- the pharmaceutical composition of the present invention can comprise 5-60% cefpodoxime proxetil; 5-50% potassium clavulanate; 0,5-5% glidant; 0,1-5% lubricant; 0,1-25% disintegrant and/or disintegrants; 1-30% diluent; 0,1-5% surfactant and optionally coating agent of 1-5% of the core weight.
- the pharmaceutical composition comprising cefpodoxime proxetil and clavulanic acid prepared according to the present invention can be in conventional tablet, film coated tablet, sachet or capsule form.
- the present invention relates to processes for preparation of pharmaceutical compositions comprising pharmaceutically acceptable excipients in addition to cefpodoxime proxetil and clavulanic acid or its derivatives as the active agents.
- the process of the present invention comprises the steps of granulating the active agent cefpodoxime proxetil and clavulanic acid or its derivatives by conventional wet and/or dry granulation methods; or powdering cefpodoxime proxetil, clavulanic acid derivatives and other excipients after mixing them by dry blending method and - compressing the pharmaceutical composition of the present invention in tablet form and optionally coating the tablets with a coating agent in the case that the product is developed in tablet form and/or,
- 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.
- the pharmaceutical composition prepared according to the present invention is used in the production of a medicament so as to be used in upper respiratory infections such as ear, nose, throat, otitis media, sinusitis, tonsillitis, pharyngitis; lower respiratory tract infections such as pyelonephritis, cystitis and urethritis; skin or soft tissue infections such as froncle, pyoderma, impetigo; in the treatment and prophylaxis of gonorrhea and lyme diseases.
- upper respiratory infections such as ear, nose, throat, otitis media, sinusitis, tonsillitis, pharyngitis
- lower respiratory tract infections such as pyelonephritis, cystitis and urethritis
- skin or soft tissue infections such as froncle, pyoderma, impetigo
- in the treatment and prophylaxis of gonorrhea and lyme diseases in the production of a medicament so as to be used in upper respiratory infections such as
- composition of the present invention can be prepared as described below, but not limited to the examples given.
- EXAMPLE 1 Formulation and process for preparation of film tablet comprising cefpodoxime proxetil and potasium clavulanate
- a process for preparation of pharmaceutical compositions is composed of the steps of mixing and compressing cefpodoxime proxetil, the disintegrant and the diluent and then sieving them; adding the surfactant, potassium clavulanate: avicel, disintegrant, glidant and lubricant into the granules obtained and mixing them; and then compressing tablets of the mixture obtained and coating the tablets with coating material.
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Abstract
The present invention relates to pharmaceutical compositions comprising cefpodoxime proxetil and clavulanic acid and/or its derivatives as the active agents.
Description
FORMULATION COMPRISING CEFPODOXIME PROXETIL AND CLAVULANIC
ACID
The present invention relates to pharmaceutical compositions comprising cefpodoxime proxetil and clavulanic acid and/or derivatives thereof as the active agents.
Background of the Invention
Cefpodoxime proxetil (Formula 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.
Formula 1
Clavulanic acid, on the other hand, is a beta-lactamase inhibitor illustrated in Formula 2.
Formula 2
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.
The patent numbered EP0593573 comprises a formulation relating to suspension forms of beta-lactam antibiotics and beta lactamase inhibitors.
However, suspension forms are not preferred much as they have the potential of high and/or uncontrolled dose intake; there appear problems in their physical and chemical stability; they have high manufacture costs and they cause problems in use and carrying.
To this end, the inventors have aimed to develop stable oral pharmaceutical formulations which comprise cefpodoxime proxetil and clavulanic acid derivatives thereof together and eliminate the low solubility problem of cefpodoxime proxetil.
Description of the Invention:
The present invention relates to stable pharmaceutical compositions with good solubility characteristics in which cefpodoxime proxetil and clavulanic acid are formulated together. It has surprisingly been seen that when the pharmaceutical composition comprising cefpodoxime proxetil and clavulanic acid wherein
- a combination of croscarmellose sodium and microcrystalline cellulose is used as the disintegrant and
- each one of the cellulose-based disintegrants is present in an amount more than 7% by weight with respect to the weight of the unit dose is developed, dissolution of the cefpodoxime proxetil increases and dissolution time of the composition decreases.
According to this, the first aspect of the present invention is the pharmaceutical compositions comprising cefpodoxime proxetil and clavulanic acid as the active agents wherein a combination of croscarmellose and microcrystalline cellulose is used as the disintegrant and each one of the cellulose-based disintegrants is present in an amount more than 7% with respect to the unit dose.
Cefpodoxime proxetil that can be used in the pharmaceutical composition of the present invention can be in the form of its solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms or in free base form and/or a combination thereof.
Clavulanic acid that can be used in the pharmaceutical composition of the present invention can be in the form of its solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms or free base form and/or a combination thereof. Preferably, potassium clavulanate is used in the present invention.
Croscarmellose sodium used in the pharmaceutical composition according to the present invention is present in an amount more than 7%, preferably in the range of 8-15%, more preferably in the range of 9-12% with respect to unit dose amount. Although the use of croscarmellose sodium in this specified amount is more than the amount disclosed in the prior art, the inventors have found that the dissolution rate of the composition increases in contrast to expectations.
Another aspect of the present invention is the pharmaceutical compositions comprising cefpodoxime proxetil and clavulanic acid or its derivatives wherein croscarmellose sodium is preferably used in an amount in the range of 8-15%, more preferably in an amount in the range of 9-12% by weight with respect to the weight of the unit dose.
Microcrystalline cellulose used in the pharmaceutical composition according to the present invention is present in an amount more than 7%, preferably in the range of 8-15%, more preferably in the range of 9-13% with respect to unit dose amount. The inventors have found that the dissolution time reduces by 60% in the case that microcrystalline cellulose is used in said amount.
Another aspect of the present invention is the pharmaceutical compositions comprising cefpodoxime proxetil and clavulanic acid or its derivatives wherein microcrystalline cellulose is preferably used in an amount in the range of 8-15%, more preferably in an amount in the range of 9-13% by weight with respect to the weight of the unit dose.
According to these, it has been found that the use of each cellulose-based disintegrant in an amount more than 7% with respect to the unit dose has an important effect on both the increase of dissolution of cefpodoxime proxetil and decrease in dissolution time of the composition comprising cefpodoxime proxetil and clavulanic acid.
The inventors have observed that an optimum particle size of the cellulose-based disintegrant used in the composition of the present invention has a considerable effect on the disintegration and dissolution of the composition. They have found that when the particle size of microcrystalline cellulose used in the present invention is less than 100 μπι, preferably in the range of 30-90 μπι and more preferably in the range of 40-60 μιτι, the dissolution of the composition increases and also dissolution time decreases.
According to this, another aspect of the present invention is pharmaceutical compositions comprising cefpodoxime proxetil and clavulanic acid or its derivatives wherein
microcrystalline cellulose with a particle size less than 100 μηι, preferably in the range of 30- 90 μηι and more preferably in the range of 40-60 μιη is used in the disintegrant combination.
In addition to cefpodoxime proxetil, clavulanic acid, microcrystalline cellulose, croscarmellose, the formulation of the present invention can comprise various excipients such as, but not limited to, glidants, lubricants, diluents, surfactants and optionally coating agents.
The glidant that can be used in the pharmaceutical composition of the present invention can be selected from, but not limited to, a group comprising magnesium silicate, silicon dioxide, starch, talc, tribasic calcium phosphate or combinations thereof.
The lubricant that can be used in the pharmaceutical composition of the present invention can be selected from, but not limited to, a group comprising calcium stearate, magnesium stearate, polyoxyethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, talc, sodium benzoate or combinations thereof. Preferably, magnesium stearate is used as the lubricant in the pharmaceutical composition of the present invention.
The diluent that can be used in the pharmaceutical composition of the present invention can be selected from, but not limited to, a group comprising calcium carbonate, calcium sulfate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, microcrystalline cellulose, lactose, magnesium carbonate, magnesium oxide, maltodextrin, maltose, mannitol, sodium chloride, sorbitol, starch, xylitol or combinations thereof.
The surfactant that can be used in the pharmaceutical composition of the present invention can be selected from, but not limited to, a group comprising docusate sodium, sorbitan esters, cetrimide and sodium lauryl sulfate. In the present invention, sodium lauryl sulfate is preferably used as the surfactant.
The pharmaceutical composition of the present invention can comprise 20-800 mg cefpodoxime proxetil or its pharmaceutically acceptable salts, hydrates, solvates or combinations thereof in an equal amount.
The pharmaceutical composition of the present invention can comprise 50-500 mg clavulanic acid or its pharmaceutically acceptable salts, hydrates, solvates or combinations 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 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 used with microcrystalline cellulose preferably in the ratio of 1 : 1.
The pharmaceutical composition of the present invention can comprise 5-60% cefpodoxime proxetil in proportion to total weight of unit dose or pharmaceutically acceptable solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms thereof.
The pharmaceutical composition of the present invention can comprise 5-50% clavulanic acid in proportion to total weight of unit dose or pharmaceutically acceptable salts, hydrates, solvates or combinations thereof in an equal amount.
The pharmaceutical composition of the present invention can comprise 5-60% cefpodoxime proxetil; 5-50% potassium clavulanate; 0,5-5% glidant; 0,1-5% lubricant; 0,1-25% disintegrant and/or disintegrants; 1-30% diluent; 0,1-5% surfactant and optionally coating agent of 1-5% of the core weight.
In another aspect, the pharmaceutical composition comprising cefpodoxime proxetil and clavulanic acid prepared according to the present invention can be in conventional tablet, film coated tablet, sachet or capsule form.
In another aspect, the present invention relates to processes for preparation of pharmaceutical compositions comprising pharmaceutically acceptable excipients in addition to cefpodoxime proxetil and clavulanic acid or its derivatives as the active agents.
According to this, the process of the present invention comprises the steps of granulating the active agent cefpodoxime proxetil and clavulanic acid or its derivatives by conventional wet and/or dry granulation methods; or powdering cefpodoxime proxetil, clavulanic acid derivatives and other excipients after mixing them by dry blending method and
- compressing the pharmaceutical composition of the present invention in tablet form and optionally coating the tablets with a coating agent in the case that the product is developed in tablet form and/or,
filling the pharmaceutical composition of the present invention in capsules in the case that the product is developed in tablet form and/or,
filling the pharmaceutical composition of the present invention in packs in the case that the product is developed in sachet 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.
According to another aspect of the present invention, the pharmaceutical composition prepared according to the present invention is used in the production of a medicament so as to be used in upper respiratory infections such as ear, nose, throat, otitis media, sinusitis, tonsillitis, pharyngitis; lower respiratory tract infections such as pyelonephritis, cystitis and urethritis; skin or soft tissue infections such as froncle, pyoderma, impetigo; in the treatment and prophylaxis of gonorrhea and lyme diseases.
The pharmaceutical composition of the present invention can be prepared as described below, but not limited to the examples given.
EXAMPLE 1: Formulation and process for preparation of film tablet comprising cefpodoxime proxetil and potasium clavulanate
According to this, a process for preparation of pharmaceutical compositions is composed of the steps of mixing and compressing cefpodoxime proxetil, the disintegrant and the diluent and then sieving them; adding the surfactant, potassium clavulanate: avicel, disintegrant, glidant and lubricant into the granules obtained and mixing them; and then compressing tablets of the mixture obtained and coating the tablets with coating material.
Claims
1. A pharmaceutical composition composed of a combination of cefpodoxime proxetil and clavulanic acid or its derivatives, wherein;
said composition comprises a combination of croscarmellose sodium and microcrystalline cellulose mixture as the disintegrant
- each one of the cellulose-based disintegrants is present in an amount more than 7% by weight with respect to the weight of the unit dose.
2. The pharmaceutical composition according to claim 1, wherein cefpodoxime proxetil comprised in said composition is in the form of its solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms or in free form and/or combinations thereof.
3. The pharmaceutical composition according to claim 1, wherein clavulanic acid comprised in said composition is in the form of its solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms or in free form and/or combinations thereof.
4. The pharmaceutical composition according to claim 3, wherein potassium clavulanate is used in said composition.
5. The pharmaceutical composition according to claim 1, wherein said composition comprises 8-15% croscarmellose sodium.
6. The pharmaceutical composition according to claim 5, wherein said composition comprises 9-12% croscarmellose sodium.
7. The pharmaceutical composition according to claim 1, wherein the particle size of microcrystalline cellulose used is less than 100 μπι.
8. The pharmaceutical composition according to claim 7, wherein the particle size of microcrystalline cellulose used is in the range of 30-90 μιη.
9. The pharmaceutical composition according to claim 8, wherein the particle size of microcrystalline cellulose used is in the range of 40-60 μιη.
10. The pharmaceutical composition according to claim 1, wherein said composition comprises 8-15% microcrystalline cellulose.
11. The pharmaceutical composition according to claim 10, wherein said composition comprises 9-13% microcrystalline cellulose.
12. The pharmaceutical composition according to claim 1, wherein said composition comprises one or more excipients such as glidant, lubricant, surfactant and optionally coating agents in addition to cefpodoxime proxetil, potassium clavulanate, microcrystalline cellulose and croscarmellose sodium.
13. The pharmaceutical composition according to claim 12, wherein the diluent is selected from a group comprising calcium carbonate, calcium sulfate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, microcrystalline cellulose, lactose, magnesium carbonate, magnesium oxide, maltodextrin, maltose, mannitol, sodium chloride, sorbitol, starch, xylitol or combinations thereof.
14. The pharmaceutical composition according to claim 12, wherein the glidant is selected from a group comprising magnesium silicate, silicon dioxide, starch, talc, tribasic calcium phosphate or combinations thereof.
15. The pharmaceutical composition according to claim 12, wherein the lubricant is selected from a group comprising calcium stearate, magnesium stearate, polyoxyethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, talc, sodium benzoate or combinations thereof.
16. The pharmaceutical composition according to claim 15, wherein magnesium stearate is used as the lubricant in said formulation.
17. The pharmaceutical composition according to claim 12, wherein the surfactant is selected from a group comprising docusate sodium, sorbitan esters, cetrimide and sodium lauryl sulfate.
18. The pharmaceutical composition according to claim 1, wherein said composition comprises 20-800 mg cefpodoxime proxetil or its pharmaceutically acceptable salts, hydrates, solvates or combinations thereof in an equal amount.
19. The pharmaceutical composition according to claim 1, wherein said composition comprises 50-500 mg clavulanic acid or its pharmaceutically acceptable salts, hydrates, solvates or combinations thereof in an equal amount.
20. The pharmaceutical composition according to claim 1 , wherein clavulanic acid or its derivative is used with a humectant in the ratio of 1 : 1.
21. The pharmaceutical composition according to claim 20, wherein the humectant to be used together with clavulanic acid is selected from a group comprising silica, colloidal silicon dioxide, magnesium trisilicate, cellulose powder, magnesium oxide, calcium silicate, starch, talc or microcrystalline cellulose.
22. The pharmaceutical composition according to claim 21, wherein the humectant to be used together with clavulanic acid is microcrystalline cellulose.
23. The pharmaceutical composition according to claim 1, wherein said composition comprises 5-60% cefpodoxime proxetil or pharmaceutically acceptable solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms thereof in an equal amount.
24. The pharmaceutical composition according to claim 1, wherein said composition comprises 5-50% clavulanic acid or pharmaceutically acceptable solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms thereof in an equal amount.
25. The pharmaceutical composition according to claim 1, wherein said composition comprises 5-60% cefpodoxime proxetil; 5-50% potassium clavulanate; 0,5-5% glidant; 0,1-5% lubricant; 0,1-25% disintegrant and/or disintegrants; 1-30% diluent; 0,1-5% surfactant in proportion to total weight of unit dose amount and optionally coating agent of 1-5%) of the core weight.
26. The pharmaceutical composition according to claim 1, wherein said composition is used in conventional tablet, film coated tablet, sachet or capsule.
27. A process for preparation of the pharmaceutical composition claimed in claim 1, wherein said process composes the steps of granulating the active agents cefpodoxime proxetil and clavulanic acid or its derivatives by conventional wet and/or dry granulation methods; or powdering cefpodoxime proxetil, clavulanic acid and other excipients after mixing them by dry blending method.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR201004467 | 2010-06-03 | ||
| PCT/TR2011/000148 WO2011152808A1 (en) | 2010-06-03 | 2011-06-02 | Formulation comprising cefpodoxime proxetil and clavulanic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP2575777A1 true EP2575777A1 (en) | 2013-04-10 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP11770579.8A Withdrawn EP2575777A1 (en) | 2010-06-03 | 2011-06-02 | Formulation comprising cefpodoxime proxetil and clavulanic acid |
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| Country | Link |
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| EP (1) | EP2575777A1 (en) |
| WO (1) | WO2011152808A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013151517A1 (en) * | 2012-04-04 | 2013-10-10 | Mahmut Bilgic | Tablet formulations comprising cefpodoxime proxetil and clavulanic acid |
| WO2014123500A1 (en) * | 2013-02-11 | 2014-08-14 | Bilgiç Mahmut | Pharmaceutical formulations comprising cefpodoxime proxetil and clavulanic acid |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4486425A (en) | 1980-09-30 | 1984-12-04 | Sankyo Company Limited | 7-[2-(2-Aminothiazol-4-yl)-2-(syn)-methoxyiminoacetamido]-3-methoxymethyl-3-cephem-4-carboxylates |
| GB9114950D0 (en) | 1991-07-11 | 1991-08-28 | Smithkline Beecham Plc | Pharmaceutical formulation |
| US5837292A (en) * | 1996-07-03 | 1998-11-17 | Yamanouchi Europe B.V. | Granulate for the preparation of fast-disintegrating and fast-dissolving compositions containing a high amount of drug |
| KR20050062514A (en) * | 2002-07-16 | 2005-06-23 | 랜박시 래보러터리스 리미티드 | Dispersible tablets for oral administration |
| EA012296B1 (en) * | 2004-01-06 | 2009-08-28 | Панацея Биотек Лтд. | Controlled release pharmaceutical composition comprising an acid-insoluble polymer and a bioadhesive polymer |
| CA2644911A1 (en) * | 2006-03-24 | 2007-10-04 | Panacea Biotec Ltd. | Antibiotic compositions of modified release and process of production thereof |
-
2011
- 2011-06-02 EP EP11770579.8A patent/EP2575777A1/en not_active Withdrawn
- 2011-06-02 WO PCT/TR2011/000148 patent/WO2011152808A1/en not_active Ceased
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| See also references of WO2011152808A1 * |
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