EP2833873A1 - Film tablet formulations comprising cefuroxime axetil and clavulanic acid - Google Patents
Film tablet formulations comprising cefuroxime axetil and clavulanic acidInfo
- Publication number
- EP2833873A1 EP2833873A1 EP13724645.0A EP13724645A EP2833873A1 EP 2833873 A1 EP2833873 A1 EP 2833873A1 EP 13724645 A EP13724645 A EP 13724645A EP 2833873 A1 EP2833873 A1 EP 2833873A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- formulation
- formulation according
- cellulose
- comprised
- weight
- 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- Withdrawn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
- KEJCWVGMRLCZQQ-YJBYXUATSA-N Cefuroxime axetil Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(=O)OC(C)OC(C)=O)=O)C(=O)\C(=N/OC)C1=CC=CO1 KEJCWVGMRLCZQQ-YJBYXUATSA-N 0.000 title claims abstract description 36
- 229960002620 cefuroxime axetil Drugs 0.000 title claims abstract description 36
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 title claims abstract description 26
- 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 26
- 229960003324 clavulanic acid Drugs 0.000 title claims abstract description 26
- 239000007916 tablet composition Substances 0.000 title description 12
- 239000000203 mixture Substances 0.000 claims abstract description 97
- 238000009472 formulation Methods 0.000 claims abstract description 86
- 239000007941 film coated tablet Substances 0.000 claims abstract description 11
- 239000003085 diluting agent Substances 0.000 claims description 24
- 239000007884 disintegrant Substances 0.000 claims description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 14
- 229960001668 cefuroxime Drugs 0.000 claims description 12
- JFPVXVDWJQMJEE-IZRZKJBUSA-N cefuroxime Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)\C(=N/OC)C1=CC=CO1 JFPVXVDWJQMJEE-IZRZKJBUSA-N 0.000 claims description 12
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 10
- 239000003906 humectant Substances 0.000 claims description 10
- 239000000314 lubricant Substances 0.000 claims description 10
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 10
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 10
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 10
- 239000011230 binding agent Substances 0.000 claims description 9
- 235000010980 cellulose Nutrition 0.000 claims description 9
- 229920002678 cellulose Polymers 0.000 claims description 9
- 239000001913 cellulose Substances 0.000 claims description 9
- 239000003826 tablet Substances 0.000 claims description 8
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 6
- 229920002472 Starch Polymers 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
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 claims description 6
- ABVRVIZBZKUTMK-JSYANWSFSA-M potassium clavulanate Chemical group [K+].[O-]C(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 ABVRVIZBZKUTMK-JSYANWSFSA-M 0.000 claims description 6
- 239000000377 silicon dioxide Substances 0.000 claims description 6
- 235000012239 silicon dioxide Nutrition 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
- 229910052623 talc Inorganic materials 0.000 claims description 6
- 235000012222 talc Nutrition 0.000 claims description 6
- 239000007888 film coating Substances 0.000 claims description 5
- 238000009501 film coating Methods 0.000 claims description 5
- -1 glidant Substances 0.000 claims description 5
- 229920000609 methyl cellulose Polymers 0.000 claims description 5
- 239000001923 methylcellulose Substances 0.000 claims description 5
- 235000010981 methylcellulose Nutrition 0.000 claims description 5
- 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 4
- 239000005995 Aluminium silicate Substances 0.000 claims description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 4
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 4
- 235000012211 aluminium silicate Nutrition 0.000 claims description 4
- PZZYQPZGQPZBDN-UHFFFAOYSA-N aluminium silicate Chemical compound O=[Al]O[Si](=O)O[Al]=O PZZYQPZGQPZBDN-UHFFFAOYSA-N 0.000 claims description 4
- 229910000323 aluminium silicate Inorganic materials 0.000 claims description 4
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 claims description 4
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 239000011248 coating agent Substances 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
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims description 4
- 239000011777 magnesium Substances 0.000 claims description 4
- 229910052749 magnesium Inorganic materials 0.000 claims description 4
- 235000001055 magnesium Nutrition 0.000 claims description 4
- 239000000391 magnesium silicate 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
- 238000000034 method Methods 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 4
- 239000011591 potassium Substances 0.000 claims description 4
- 229910052700 potassium Inorganic materials 0.000 claims description 4
- 229940069328 povidone Drugs 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims description 4
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 3
- 229940071676 hydroxypropylcellulose Drugs 0.000 claims description 3
- 229940091250 magnesium supplement Drugs 0.000 claims description 3
- 238000005550 wet granulation Methods 0.000 claims description 3
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 2
- 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 2
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 claims description 2
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 2
- 239000001856 Ethyl cellulose Substances 0.000 claims description 2
- 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 2
- 239000001828 Gelatine Substances 0.000 claims description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 2
- 239000008118 PEG 6000 Substances 0.000 claims description 2
- 229920002584 Polyethylene Glycol 6000 Polymers 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
- 229920002301 cellulose acetate Polymers 0.000 claims description 2
- 239000008119 colloidal silica Substances 0.000 claims description 2
- 229940075614 colloidal silicon dioxide Drugs 0.000 claims description 2
- 238000007906 compression Methods 0.000 claims description 2
- 230000006835 compression Effects 0.000 claims description 2
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 2
- 229960000913 crospovidone Drugs 0.000 claims description 2
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 2
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 2
- 229920001249 ethyl cellulose Polymers 0.000 claims description 2
- 239000012458 free base Chemical group 0.000 claims description 2
- 229920000159 gelatin Polymers 0.000 claims description 2
- 235000019322 gelatine Nutrition 0.000 claims description 2
- 150000004677 hydrates Chemical class 0.000 claims description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
- 229960003943 hypromellose Drugs 0.000 claims description 2
- 235000010445 lecithin Nutrition 0.000 claims description 2
- 239000000787 lecithin Substances 0.000 claims description 2
- 229940067606 lecithin Drugs 0.000 claims description 2
- 238000005461 lubrication Methods 0.000 claims description 2
- 239000000395 magnesium oxide Substances 0.000 claims description 2
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 2
- 235000012245 magnesium oxide Nutrition 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
- 229910000386 magnesium trisilicate Inorganic materials 0.000 claims description 2
- 235000019793 magnesium trisilicate Nutrition 0.000 claims description 2
- 229940099273 magnesium trisilicate Drugs 0.000 claims description 2
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims description 2
- 229960002900 methylcellulose Drugs 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
- 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
- 239000000843 powder Substances 0.000 claims description 2
- 229960001866 silicon dioxide Drugs 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
- 239000012453 solvate Substances 0.000 claims description 2
- 239000004408 titanium dioxide Substances 0.000 claims description 2
- 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 claims description 2
- 235000019731 tricalcium phosphate Nutrition 0.000 claims description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims 1
- 238000001035 drying Methods 0.000 claims 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims 1
- 229940071826 hydroxyethyl cellulose Drugs 0.000 claims 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 claims 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000007873 sieving Methods 0.000 claims 1
- 238000011282 treatment Methods 0.000 abstract description 5
- 241000894006 Bacteria Species 0.000 abstract description 4
- 206010017553 Furuncle Diseases 0.000 abstract description 4
- 206010018612 Gonorrhoea Diseases 0.000 abstract description 4
- 206010021531 Impetigo Diseases 0.000 abstract description 4
- 206010024971 Lower respiratory tract infections Diseases 0.000 abstract description 4
- 208000016604 Lyme disease Diseases 0.000 abstract description 4
- 206010033078 Otitis media Diseases 0.000 abstract description 4
- 201000007100 Pharyngitis Diseases 0.000 abstract description 4
- 206010037596 Pyelonephritis Diseases 0.000 abstract description 4
- 208000006311 Pyoderma Diseases 0.000 abstract description 4
- 206010057190 Respiratory tract infections Diseases 0.000 abstract description 4
- 206010062255 Soft tissue infection Diseases 0.000 abstract description 4
- 206010046306 Upper respiratory tract infection Diseases 0.000 abstract description 4
- 201000003146 cystitis Diseases 0.000 abstract description 4
- 208000001786 gonorrhea Diseases 0.000 abstract description 4
- 208000015181 infectious disease Diseases 0.000 abstract description 4
- 238000011321 prophylaxis Methods 0.000 abstract description 4
- 208000020029 respiratory tract infectious disease Diseases 0.000 abstract description 4
- 201000009890 sinusitis Diseases 0.000 abstract description 4
- 206010040872 skin infection Diseases 0.000 abstract description 4
- 206010044008 tonsillitis Diseases 0.000 abstract description 4
- 208000000143 urethritis Diseases 0.000 abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 3
- 239000010408 film Substances 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 5
- 230000017531 blood circulation Effects 0.000 description 5
- 230000002496 gastric effect Effects 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 239000007935 oral tablet Substances 0.000 description 2
- 229940096978 oral tablet Drugs 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000002132 β-lactam antibiotic Substances 0.000 description 1
- 229940124586 β-lactam antibiotics Drugs 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
- 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
- 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
- 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
Definitions
- the present invention relates to pharmaceutical formulations comprising cefuroxime axetil and clavulanic acid for use in treatment and prophylaxis of gram positive and gram negative bacteria-related upper respiratory tract infections such as otorhinolaryngological infections, otitis media, sinusitis, tonsillitis, pharyngitis; lower respiratory tract infections such as pyelonephritis, cystitis and urethritis; skin and soft tissue infections such as furuncle, pyoderma, impetigo; gonorrhea and lyme diseases.
- Said formulations are characterized in being in film coated tablet form.
- Cefuroxime was first disclosed in the application numbered US3974153.
- cefuroxime is effective in treatment and prophylaxis of gram positive and gram negative bacteria-related upper respiratory tract infections such as otorhinolaryngological infections, otitis media, sinusitis, tonsillitis, pharyngitis; lower respiratory tract infections such as pyelonephritis, cystitis and urethritis; skin and soft tissue infections such as furuncle, pyoderma, impetigo; gonorrhea and lyme diseases.
- upper respiratory tract infections such as otorhinolaryngological infections, otitis media, sinusitis, tonsillitis, pharyngitis
- lower respiratory tract infections such as pyelonephritis, cystitis and urethritis
- skin and soft tissue infections such as furuncle, pyoderma, impetigo; gonorrhea and lyme diseases.
- Cefuroxime is found in form of 125, 250 and 500 mg tablet and suspension on the market.
- cefuroxime axetil which is ester form of cefuroxime
- cefuroxime axetil is a pretty effective beta- lactam antibiotic against a broad spectrum of microorganisms
- bioavailability of cefuroxime required to enable its absorption through the blood circulation by the gastrointestinal tract is low.
- the reasons for this are low solubility of cefuroxime in aqueous solutions and its stability problems.
- difficulties of providing high bioavailability for orally administrable cefuroxime axetil formulations are mentioned.
- cefuroxime axetil provide good bioavailability when cefuroxime axetil is used in pure amorphous form or high amounts of disintegrant are used to enable quick dissolution in gastrointestinal liquid.
- tablet forms are developed comprising combinations of a beta-lactam group cephalosporin antibiotic such as cefuroxime axetil and a beta-lactam inhibitor such as clavulanic acid in order to prevent bacterial resistance and provide an even higher antibacterial resistance.
- a beta-lactam group cephalosporin antibiotic such as cefuroxime axetil
- a beta-lactam inhibitor such as clavulanic acid
- problems of solubility and stability seen in cefuroxime axetil formulations are more prominent in tablet formulations comprising cefuroxime axetil and clavulanic acid in the prior art since clavulanic acid has a high potential to absorb moisture due to its hygroscopic nature. This results in observation of instability in oral tablet forms comprising cefuroxime axetil and clavulanic acid, therefore low solubility and low bioavailability during use.
- the formulations comprising cefuroxime axetil and clavulanic acid and formulated in film coated tablet form are stabile and have high solubility in gastrointestinal liquid, therefore their absorption through blood circulation increases in the case that they comprise at least one cellulose based diluent and the ratio of cefuroxime axetil: diluent is in the range of 1 :5 to 5:1 by weight.
- the present invention relates to formulations comprising cefuroxime axetil and clavulanic acid formulated in film coated tablet form and is characterized in that said formulations comprise at least one cellulose based diluent and the ratio of cefuroxime axetihdiluent is in the range of 1 :5 to 5: 1 by weight.
- Characteristic features of the film coated tablet formulations of the present invention are that they are stabile, present high solubility and fast dispersion during use and therefore have high bioavailability as their absorption through the blood circulation increases as a result of comprising at least one cellulose based diluent and having the ratio of cefuroxime axetil .-diluent in the range of 1 :5 to 5:1 by weight.
- the present invention relates to formulations formulated in film coated tablet form comprising cefuroxime axetil and clavulanic acid, and it is characterized in comprising at least one cellulose based diluent and having the ratio of cefuroxime axetihdiluent preferably in the range of 1 :2 to 4: 1 by weight.
- the diluent used in the formulations of the present invention can be selected from a group comprising microcrystalline cellulose, silicified microcrystalline, cellulose acetate, modified cellulose and/or combinations thereof.
- microcrystalline cellulose can be used as diluent in the tablet formulations prepared according to the present invention.
- the tablet formulations of the present invention comprise at least one pharmaceutically acceptable excipient in addition to cefuroxime axetil, clavulanic acid and the diluent.
- the pharmaceutically acceptable excipients that can be used in the formulations of the present invention can be selected from a group comprising disintegrant, glidant, lubricant, binder, humectant and film coating agent.
- the disintegrant that can be used in the tablet formulations of the present invention comprising cefuroxime axetil and clavulanic acid can be selected from a group comprising carboxymethyl cellulose calcium, carboxymethyl cellulose sodium, microcrystalline cellulose, silicon dioxide, croscarmellose sodium, crospovidone, hydroxypropyl cellulose, methylcellulose, povidone, magnesium aluminium silicate, starch.
- carboxymethyl cellulose sodium or carboxymethyl cellulose calcium or a disintegrant composition comprising the combination thereof can be used as disintegrant in the formulations of the present invention. More preferably, carboxymethyl cellulose calcium can be used.
- the film tablet formulations comprising cefuroxime axetil and clavulanic acid to disperse fast and homogeneously in body and provide an effective treatment during use.
- the inventors have seen that optimum hardness and brittleness values are attained and thus the formulations can disperse fast and homogeneously as desired in the case that the film tablet formulations comprising cefuroxime axetil and clavulanic acid comprise a diluent and a disintegrant such that the ratio of diluen disintegrant is in the range of 1 : 1 to 6: 1 , preferably in the range of 2: 1 to 5 : 1 by weight.
- Another characteristic of the tablet formulations of the present invention comprising cefuroxime axetil and clavulanic acid is that the ratio of diluent:disintegrant is in the range of 1 :1 to 6: 1, preferably in the range of 2: 1 to 5:1 by weight.
- the glidant that can be used in the formulations of the present invention can be selected from a group comprising magnesium silicate, silicon dioxide, colloidal silicon dioxide, starch, talc, tribasic calcium phosphate or combinations thereof.
- silicon dioxide can be used as the glidant in the formulations of the present invention.
- the lubricant that can be used in the formulations prepared according to the present invention can be selected form a group comprising calcium stearate, magnesium stearate, sodium stearyl fumarate, polyethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, sodium benzoate.
- sodium stearyl fumarate can be used as the lubricant in the formulations of the present invention.
- the binder that can be used in the formulations of the present invention can be selected from a group comprising ethyl cellulose, gelatine, hydroxyl ethyl cellulose, hydroxyl methyl cellulose, hydroxyl propyl cellulose, hypromellose, magnesium aluminium silicate, methyl cellulose, povidone.
- the humectant that can be used in the tablet formulations of the present invention comprising cefuroxime axetil and clavulanic acid can be selected from a group comprising silica, colloidal silica, magnesium trisilicate, powder cellulose, microcrystalline cellulose, magnesium oxide, calcium silicate, starch, microcrystalline cellulose and talc.
- Clavulanic acid can be in the form of its solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts and free base, polymorphous forms, crystalline forms, amorphous forms and esters.
- Clavulanic acid used as the second active agent in addition to cefuroxime in the tablet formulations of the present invention comprising cefuroxime is preferably in potassium clavulanate form. Another characteristic of the formulations of the present invention is that the ratio of potassium clavulanate :humectant is 1 : 1.
- the film coating agent that can be used in the film coated tablet formulations prepared according to the present invention can be selected from a group comprising polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, lecithin or a combination thereof.
- the film coating agent marketed under the name of Opadry Yellow® can be used.
- formulations of the present invention comprise cefuroxime axetil in the range of 5-80%, preferably in the range of 20-70%, more preferably in the range of 30-60% by weight in proportion to total weight of the unit dose amount.
- formulations comprise potassium clavulanate-humectant mixture in the range of 10-50%, preferably in the range of 10-40%, more preferably in the range of 15-35% by weight in proportion to total weight of the unit dose amount.
- the formulations prepared according to the present invention can comprise 5-30% diluent, 1- 10% disintegrant, 0.1-2% binder, 0.1-2% glidant, 0.1-2% lubricant, 0.5-2.5% coating agent by weight in proportion to total weight of the unit dose amount.
- wet granulation method is used for preparation of the formulation of the present invention.
- the granulation solution prepared using binder and purified water is used to granulate the mixture comprising sieved cefuroxime axetil, diluent and disintegrant.
- potassium clavulanate, diluent, disintegrant and glidant are added to the mixture and they are mixed again.
- lubrication is applied with the lubricant and the final mixture obtained is compressed in tablet form.
- the tablets compressed are coated with film.
- the film coated tablets are blistered and put into cartons.
- the formulations of the present invention can be used in treatment and prophylaxis of gram positive and gram negative bacteria-related upper respiratory tract infections such as otorhinolaryngological infections, otitis media, sinusitis, tonsillitis, pharyngitis; lower respiratory tract infections such as pyelonephritis, cystitis and urethritis; skin and soft tissue infections such as furuncle, pyoderma, impetigo; gonorrhea and lyme diseases.
- upper respiratory tract infections such as otorhinolaryngological infections, otitis media, sinusitis, tonsillitis, pharyngitis
- lower respiratory tract infections such as pyelonephritis, cystitis and urethritis
- skin and soft tissue infections such as furuncle, pyoderma, impetigo; gonorrhea and lyme diseases.
- Example I Tablet formulation comprising cefuroxime axetil and clavulanic acid
- the formulation given above is prepared by wet granulation method. After cefuroxime axetil and potassium clavulanate are granulated with the granulation solution comprising binder; the granules are mixed with the mixture comprising diluent, disintegrant, binder and glidant in the container. The mixture lubricated with the lubricant is sent to tablet compression. The tablets are coated with film, blistered and put into cartons.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to pharmaceutical formulations comprising cefuroxime axetil and clavulanic acid for use in treatment and prophylaxis of gram positive and gram negative bacteria-related upper respiratory tract infections such as otorhinolaryngological infections, otitis media, sinusitis, tonsillitis, pharyngitis; lower respiratory tract infections such as pyelonephritis, cystitis and urethritis; skin and soft tissue infections such as furuncle, pyoderma, impetigo; gonorrhea and lyme diseases. Said formulations are characterized in being in film coated tablet form.
Description
FILM TABLET FORMULATIONS COMPRISING CEFUROXIME AXETIL AND
CLAVULANIC ACID
The present invention relates to pharmaceutical formulations comprising cefuroxime axetil and clavulanic acid for use in treatment and prophylaxis of gram positive and gram negative bacteria-related upper respiratory tract infections such as otorhinolaryngological infections, otitis media, sinusitis, tonsillitis, pharyngitis; lower respiratory tract infections such as pyelonephritis, cystitis and urethritis; skin and soft tissue infections such as furuncle, pyoderma, impetigo; gonorrhea and lyme diseases. Said formulations are characterized in being in film coated tablet form. Cefuroxime was first disclosed in the application numbered US3974153. It has been disclosed in said document that use of cefuroxime is effective in treatment and prophylaxis of gram positive and gram negative bacteria-related upper respiratory tract infections such as otorhinolaryngological infections, otitis media, sinusitis, tonsillitis, pharyngitis; lower respiratory tract infections such as pyelonephritis, cystitis and urethritis; skin and soft tissue infections such as furuncle, pyoderma, impetigo; gonorrhea and lyme diseases.
Cefuroxime is found in form of 125, 250 and 500 mg tablet and suspension on the market.
Although cefuroxime axetil, which is ester form of cefuroxime, is a pretty effective beta- lactam antibiotic against a broad spectrum of microorganisms, it is known that bioavailability of cefuroxime required to enable its absorption through the blood circulation by the gastrointestinal tract is low. The reasons for this are low solubility of cefuroxime in aqueous solutions and its stability problems.
In the prior art, difficulties of providing high bioavailability for orally administrable cefuroxime axetil formulations are mentioned.
In the patent numbered US4820833, it was disclosed that solubility of pure amorphous form of cefuroxime in oral dosage forms is higher compared to its crystalline forms and has a better bioavailability.
In the patent numbered US4897270, it was seen that absorption of film coated cefuroxime axetil formulations through blood circulation remains low unless coating is formulated to disperse quickly when the film-coated tablet reaches the stomach.
According to the prior art, it is seen that oral forms of cefuroxime axetil provide good bioavailability when cefuroxime axetil is used in pure amorphous form or high amounts of disintegrant are used to enable quick dissolution in gastrointestinal liquid.
Furthermore, tablet forms are developed comprising combinations of a beta-lactam group cephalosporin antibiotic such as cefuroxime axetil and a beta-lactam inhibitor such as clavulanic acid in order to prevent bacterial resistance and provide an even higher antibacterial resistance. However, problems of solubility and stability seen in cefuroxime axetil formulations are more prominent in tablet formulations comprising cefuroxime axetil and clavulanic acid in the prior art since clavulanic acid has a high potential to absorb moisture due to its hygroscopic nature. This results in observation of instability in oral tablet forms comprising cefuroxime axetil and clavulanic acid, therefore low solubility and low bioavailability during use.
According to the problems mentioned in the prior art, there is need for development of stabile oral tablet formulations comprising cefuroxime axetil and clavulanic acid combination which have high solubility in gastrointestinal liquid, high absorption through the blood circulation by the gastrointestinal tract and therefore high bioavailability. The inventors have seen that film coated tablet forms comprising cefuroxime axetil and clavulanic acid they developed are highly stabile and they present high solubility and fast dispersion during use and thus they have high bioavailability.
The inventors have surprisingly seen that the formulations comprising cefuroxime axetil and clavulanic acid and formulated in film coated tablet form are stabile and have high solubility in gastrointestinal liquid, therefore their absorption through blood circulation increases in the
case that they comprise at least one cellulose based diluent and the ratio of cefuroxime axetil: diluent is in the range of 1 :5 to 5:1 by weight.
Description of the Invention
According to this, the present invention relates to formulations comprising cefuroxime axetil and clavulanic acid formulated in film coated tablet form and is characterized in that said formulations comprise at least one cellulose based diluent and the ratio of cefuroxime axetihdiluent is in the range of 1 :5 to 5: 1 by weight.
Characteristic features of the film coated tablet formulations of the present invention are that they are stabile, present high solubility and fast dispersion during use and therefore have high bioavailability as their absorption through the blood circulation increases as a result of comprising at least one cellulose based diluent and having the ratio of cefuroxime axetil .-diluent in the range of 1 :5 to 5:1 by weight.
According to this in another aspect, the present invention relates to formulations formulated in film coated tablet form comprising cefuroxime axetil and clavulanic acid, and it is characterized in comprising at least one cellulose based diluent and having the ratio of cefuroxime axetihdiluent preferably in the range of 1 :2 to 4: 1 by weight.
The diluent used in the formulations of the present invention can be selected from a group comprising microcrystalline cellulose, silicified microcrystalline, cellulose acetate, modified cellulose and/or combinations thereof. Preferably, microcrystalline cellulose can be used as diluent in the tablet formulations prepared according to the present invention.
Another characteristic feature of the tablet formulations of the present invention is that said formulations comprise at least one pharmaceutically acceptable excipient in addition to cefuroxime axetil, clavulanic acid and the diluent. According to this, the pharmaceutically acceptable excipients that can be used in the formulations of the present invention can be selected from a group comprising disintegrant, glidant, lubricant, binder, humectant and film coating agent.
The disintegrant that can be used in the tablet formulations of the present invention comprising cefuroxime axetil and clavulanic acid can be selected from a group comprising
carboxymethyl cellulose calcium, carboxymethyl cellulose sodium, microcrystalline cellulose, silicon dioxide, croscarmellose sodium, crospovidone, hydroxypropyl cellulose, methylcellulose, povidone, magnesium aluminium silicate, starch.
Preferably, carboxymethyl cellulose sodium or carboxymethyl cellulose calcium or a disintegrant composition comprising the combination thereof can be used as disintegrant in the formulations of the present invention. More preferably, carboxymethyl cellulose calcium can be used.
Physical characteristics of the tablets such as hardness and brittleness are required to be at optimum values in order for the film tablet formulations comprising cefuroxime axetil and clavulanic acid to disperse fast and homogeneously in body and provide an effective treatment during use. The inventors have seen that optimum hardness and brittleness values are attained and thus the formulations can disperse fast and homogeneously as desired in the case that the film tablet formulations comprising cefuroxime axetil and clavulanic acid comprise a diluent and a disintegrant such that the ratio of diluen disintegrant is in the range of 1 : 1 to 6: 1 , preferably in the range of 2: 1 to 5 : 1 by weight.
Another characteristic of the tablet formulations of the present invention comprising cefuroxime axetil and clavulanic acid is that the ratio of diluent:disintegrant is in the range of 1 :1 to 6: 1, preferably in the range of 2: 1 to 5:1 by weight.
The glidant that can be used in the formulations of the present invention can be selected from a group comprising magnesium silicate, silicon dioxide, colloidal silicon dioxide, starch, talc, tribasic calcium phosphate or combinations thereof.
Preferably, silicon dioxide can be used as the glidant in the formulations of the present invention.
The lubricant that can be used in the formulations prepared according to the present invention can be selected form a group comprising calcium stearate, magnesium stearate, sodium stearyl fumarate, polyethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, sodium benzoate.
Preferably, sodium stearyl fumarate can be used as the lubricant in the formulations of the present invention.
The binder that can be used in the formulations of the present invention can be selected from a group comprising ethyl cellulose, gelatine, hydroxyl ethyl cellulose, hydroxyl methyl cellulose, hydroxyl propyl cellulose, hypromellose, magnesium aluminium silicate, methyl cellulose, povidone. The humectant that can be used in the tablet formulations of the present invention comprising cefuroxime axetil and clavulanic acid can be selected from a group comprising silica, colloidal silica, magnesium trisilicate, powder cellulose, microcrystalline cellulose, magnesium oxide, calcium silicate, starch, microcrystalline cellulose and talc.
Clavulanic acid can be in the form of its solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts and free base, polymorphous forms, crystalline forms, amorphous forms and esters.
Clavulanic acid used as the second active agent in addition to cefuroxime in the tablet formulations of the present invention comprising cefuroxime is preferably in potassium clavulanate form. Another characteristic of the formulations of the present invention is that the ratio of potassium clavulanate :humectant is 1 : 1.
The film coating agent that can be used in the film coated tablet formulations prepared according to the present invention can be selected from a group comprising polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, lecithin or a combination thereof. For instance, the film coating agent marketed under the name of Opadry Yellow® can be used.
Another characteristic of the formulations of the present invention is that said formulations comprise cefuroxime axetil in the range of 5-80%, preferably in the range of 20-70%, more preferably in the range of 30-60% by weight in proportion to total weight of the unit dose amount. Another characteristic of the formulations of the present invention is that said formulations comprise potassium clavulanate-humectant mixture in the range of 10-50%, preferably in the range of 10-40%, more preferably in the range of 15-35% by weight in proportion to total weight of the unit dose amount.
The formulations prepared according to the present invention can comprise 5-30% diluent, 1- 10% disintegrant, 0.1-2% binder, 0.1-2% glidant, 0.1-2% lubricant, 0.5-2.5% coating agent by weight in proportion to total weight of the unit dose amount.
Preferably, wet granulation method is used for preparation of the formulation of the present invention. According to this method, the granulation solution prepared using binder and purified water is used to granulate the mixture comprising sieved cefuroxime axetil, diluent and disintegrant. After the obtained granules are dried and sieved; potassium clavulanate, diluent, disintegrant and glidant are added to the mixture and they are mixed again. At the last phase, lubrication is applied with the lubricant and the final mixture obtained is compressed in tablet form. The tablets compressed are coated with film. The film coated tablets are blistered and put into cartons.
The formulations of the present invention can be used in treatment and prophylaxis of gram positive and gram negative bacteria-related upper respiratory tract infections such as otorhinolaryngological infections, otitis media, sinusitis, tonsillitis, pharyngitis; lower respiratory tract infections such as pyelonephritis, cystitis and urethritis; skin and soft tissue infections such as furuncle, pyoderma, impetigo; gonorrhea and lyme diseases.
The examples below are given in order to explain the pharmaceutical compositions of the present invention and their preparation methods, yet the invention cannot be limited to these.
Example I. Tablet formulation comprising cefuroxime axetil and clavulanic acid
The formulation given above is prepared by wet granulation method. After cefuroxime axetil and potassium clavulanate are granulated with the granulation solution comprising binder; the granules are mixed with the mixture comprising diluent, disintegrant, binder and glidant in the container. The mixture lubricated with the lubricant is sent to tablet compression. The tablets are coated with film, blistered and put into cartons.
Claims
1. A formulation comprising cefuroxime axetil and clavulanic acid and formulated in film coated tablet form, characterized in that said formulation comprises at least one cellulose based diluent,
• the ratio of cefuroxime axetil: diluent is in the range of 1 :5 to 5 : 1 and
• the ratio of diluen disintegrant is in the range of 1 : 1 to 6: 1 by weight.
2. The formulation according to claim 1, characterized in that said formulation comprises at least one cellulose based diluent and the ratio of cefuroxime axeti diluent is in the range of 1 :2 to 4:1 by weight.
3. The formulation according to claims 1-2, characterized in that the diluent comprised in said formulation is selected from a group comprising microcrystalline cellulose, silicified microcrystalline, cellulose acetate, modified cellulose and/or a combination thereof.
4. The formulation according to claim 3, characterized in that the diluent comprised in said formulation is microcrystalline cellulose.
5. The formulation according to claims 1-4, characterized in that said formulation comprises at least one pharmaceutically acceptable excipient in addition to cefuroxime axetil, clavulanic acid and the diluent.
6. The formulation according to claim 5, characterized in that the excipients that can be comprised in said formulation are selected from a group comprising disintegrant, glidant, lubricant, binder, humectant and film coating agent.
7. The formulation according to claim 6, characterized in that the disintegrant that can be comprised in said formulation is selected from a group comprising carboxymethyl cellulose calcium, carboxymethyl cellulose sodium, microcrystalline cellulose, silicon dioxide, croscarmellose sodium, crospovidone, hydroxypropyl cellulose, methylcellulose, povidone, magnesium aluminium silicate, starch or combinations thereof.
8. The formulation according to claim 7, characterized in that the disintegrant that can be comprised in said formulation is selected from carboxymethyl cellulose sodium or carboxymethyl cellulose calcium or a disintegrant composition comprising a combination thereof.
9. The formulation according to claim 8, characterized in that the disintegrant that can be comprised in said formulation is carboxymethyl cellulose calcium.
10. The formulation according to claims 5-9, characterized in that the glidant that can be comprised in said formulation is selected from a group comprising magnesium silicate, silicon dioxide, colloidal silicon dioxide, starch, talc, tribasic calcium phosphate or a combination thereof.
1 1. The formulation according to claim 10, characterized in that the glidant that can be used in said formulations is silicon dioxide.
12. The formulation according to claims 5-1 1 , characterized in that the lubricant that can be comprised in said formulation is selected form a group comprising calcium stearate, magnesium stearate, sodium stearyl fumarate, polyethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, sodium benzoate.
13. The formulation according to claim 12, characterized in that the lubricant that can be used in said formulations is sodium stearyl fumarate.
14. The formulation according to claim 5-13, characterized in that the binder that can be comprised in said formulation is selected from a group comprising ethyl cellulose, gelatine, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminium silicate, methyl cellulose, povidone.
15. The formulation according to claims 5-14, characterized in that the humectant that can be comprised in said formulation is selected from a group comprising silica, colloidal silica, magnesium trisilicate, powder cellulose, microcrystalline cellulose, magnesium oxide, calcium silicate, starch, microcrystalline cellulose and talc.
16. The formulation according to claims 5-15, characterized in that the coating agent that can be comprised in said formulation is selected from a group comprising polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, lecithin or a combination thereof.
17. The formulation according to claims 1 -16, characterized in that the ratio of diluent:disintegrant comprised in said formulation is in the range of 2: 1 to 5: 1 by weight.
18. The formulation according to any preceding claims, characterized in that clavulanic acid comprised in said formulation is selected from a group comprising its solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts and free base form, polymorphs, crystalline forms, amorphous forms and esters.
19. The formulation according to any preceding claims, characterized in that clavulanic acid comprised in said formulation is in potassium clavulanate form.
20. The formulation according to any preceding claims, characterized in that the ratio of potassium clavulanate:humectant in said formulation is 1 : 1.
21. The formulation according to any preceding claims, characterized in that said formulation comprises 5-80% cefuroxime axetil by weight.
22. The formulation according to claim 21 , characterized in that said formulation comprises 20-70% cefuroxime axetil by weight.
23. The formulation according to claim 22, characterized in that said formulation comprises 30-60%) cefuroxime axetil by weight.
24. The formulation according to any preceding claims, characterized in that said formulation comprises potassium clavulanate-humectant mixture in the range of 10- 50% by weight.
25. The formulation according to claim 24, characterized in that said formulation comprises potassium clavulanate-humectant mixture in the range of 10-40% by weight.
26. The formulation according to claim 25, characterized in that said formulation comprises potassium clavulanate-humectant mixture in the range of 10-40% by weight.
27. The formulation according to any preceding claims, characterized in that said formulation comprises 5-30% of diluent, 1-10%> of disintegrant, 0.1-2% of binder, 0.1- 2% of glidant, 0.1-2% of lubricant, 0.5-2.5% of coating agent by weight in proportion to total weight of the unit dose amount.
28. A method for production of the formulation according to any preceding claims, characterized in that said method comprises the steps of wet granulation, drying, sieving, lubrication, tablet compression and film coating.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR201203835 | 2012-04-04 | ||
| PCT/TR2013/000107 WO2013151516A1 (en) | 2012-04-04 | 2013-04-03 | Film tablet formulations comprising cefuroxime axetil and clavulanic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP2833873A1 true EP2833873A1 (en) | 2015-02-11 |
Family
ID=48483178
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP13724645.0A Withdrawn EP2833873A1 (en) | 2012-04-04 | 2013-04-03 | Film tablet formulations comprising cefuroxime axetil and clavulanic acid |
Country Status (2)
| Country | Link |
|---|---|
| EP (1) | EP2833873A1 (en) |
| WO (1) | WO2013151516A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10420776B2 (en) | 2016-10-13 | 2019-09-24 | RhinoNase, Inc. | Antibiotic compositions for nasal irrigation and methods |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3974153A (en) | 1971-05-14 | 1976-08-10 | Glaxo Laboratories Limited | 7-Hydrocarbonoxy imino-acetamido-3-carbamoyloxy methylceph-3-em-4 carboxylic acids |
| YU44680B (en) | 1982-07-30 | 1990-12-31 | Glaxo Lab Ltd | Process for obtaining very pure amorphous form of cephuroxim axetile |
| GB8524001D0 (en) * | 1985-09-30 | 1985-11-06 | Glaxo Group Ltd | Pharmaceutical composition |
| AT500063A1 (en) * | 1999-11-23 | 2005-10-15 | Sandoz Ag | COATED TABLETS |
| US20110190253A1 (en) * | 2008-05-27 | 2011-08-04 | Blanchard John S | Method for treating tuberculosis |
| WO2013001541A1 (en) * | 2011-06-30 | 2013-01-03 | Aggarwal Kumar Vijay | An optimized bilayered tablet dosage form with high rate of bioavailability of two active antibiotics: cefuroxime and clavulanic acid |
-
2013
- 2013-04-03 WO PCT/TR2013/000107 patent/WO2013151516A1/en not_active Ceased
- 2013-04-03 EP EP13724645.0A patent/EP2833873A1/en not_active Withdrawn
Non-Patent Citations (1)
| Title |
|---|
| See references of WO2013151516A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2013151516A1 (en) | 2013-10-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2943574A1 (en) | Solid composition comprising amorphous sofosbuvir | |
| WO2012060788A1 (en) | Formulations of cephalosporins with controlled moisture content | |
| CN108136033A (en) | Include the solid composite medicament of amorphous Suo Feibuwei | |
| US20130274262A1 (en) | Pharmaceutical compositions of linezolid | |
| WO2013151518A1 (en) | Capsule formulations comprising ceftibuten | |
| WO2011142730A1 (en) | Pharmaceutical composition comprising cefixime and clavulanic acid derivative compound | |
| WO2016079687A1 (en) | Oral pharmaceutical composition of teriflunomide | |
| WO2012060786A2 (en) | Cefpodoxime proxetil formulations comprising viscosity agent | |
| WO2013151516A1 (en) | Film tablet formulations comprising cefuroxime axetil and clavulanic acid | |
| EP2608776A2 (en) | Cefpodoxime proxetil formulations | |
| EP2510922A1 (en) | Manufacturing process for tablet formulations comprising cefuroxime | |
| EP2575812A2 (en) | Pharmaceutical composition comprising cefpodoxime proxetil and clavulanic acid | |
| WO2017037645A1 (en) | Stable pharmaceutical formulations of teriflunomide | |
| WO2014123500A1 (en) | Pharmaceutical formulations comprising cefpodoxime proxetil and clavulanic acid | |
| WO2012060787A1 (en) | Oral dosage forms comprising cefdinir and carboxymethyl cellulose calcium | |
| EP2575777A1 (en) | Formulation comprising cefpodoxime proxetil and clavulanic acid | |
| WO2008045006A1 (en) | Formulations of candesartan | |
| WO2014126541A1 (en) | Pharmaceutical compositions used in treating bacterial infections | |
| WO2012060793A2 (en) | Process for the preparation of cefdinir formulations | |
| WO2011010214A1 (en) | Pharmaceutical composition of rifampicin | |
| WO2012060792A1 (en) | Pharmaceutical compositions comprising minimum 6 % of disintegrants by weight | |
| WO2013151517A1 (en) | Tablet formulations comprising cefpodoxime proxetil and clavulanic acid | |
| CA2847439A1 (en) | Compositions of imatinib | |
| EP2663289A2 (en) | Cefpodoxime proxetil formulations comprising taste regulating agent | |
| US20150093437A1 (en) | Novel pharmaceutical composition of linezolid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| 17P | Request for examination filed |
Effective date: 20141103 |
|
| AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR |
|
| AX | Request for extension of the european patent |
Extension state: BA ME |
|
| DAX | Request for extension of the european patent (deleted) | ||
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
| 18D | Application deemed to be withdrawn |
Effective date: 20151021 |