EP2515857A1 - The production method for effervescent tablet with cefdinir - Google Patents
The production method for effervescent tablet with cefdinirInfo
- Publication number
- EP2515857A1 EP2515857A1 EP10805546A EP10805546A EP2515857A1 EP 2515857 A1 EP2515857 A1 EP 2515857A1 EP 10805546 A EP10805546 A EP 10805546A EP 10805546 A EP10805546 A EP 10805546A EP 2515857 A1 EP2515857 A1 EP 2515857A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- formulation
- cefdinir
- effervescent
- water
- granulation solution
- 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- Withdrawn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
- RTXOFQZKPXMALH-GHXIOONMSA-N cefdinir Chemical compound S1C(N)=NC(C(=N\O)\C(=O)N[C@@H]2C(N3C(=C(C=C)CS[C@@H]32)C(O)=O)=O)=C1 RTXOFQZKPXMALH-GHXIOONMSA-N 0.000 title claims abstract description 37
- 229960003719 cefdinir Drugs 0.000 title claims abstract description 37
- 238000004519 manufacturing process Methods 0.000 title claims description 8
- 239000007938 effervescent tablet Substances 0.000 title description 5
- 238000000034 method Methods 0.000 claims abstract description 65
- 238000002360 preparation method Methods 0.000 claims abstract description 10
- 239000013543 active substance Substances 0.000 claims abstract description 9
- 239000000203 mixture Substances 0.000 claims description 52
- 238000009472 formulation Methods 0.000 claims description 45
- 238000005469 granulation Methods 0.000 claims description 28
- 230000003179 granulation Effects 0.000 claims description 28
- 239000000243 solution Substances 0.000 claims description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 25
- 235000003599 food sweetener Nutrition 0.000 claims description 15
- 235000002639 sodium chloride Nutrition 0.000 claims description 15
- 239000003765 sweetening agent Substances 0.000 claims description 15
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 claims description 13
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 claims description 13
- 239000008187 granular material Substances 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 12
- 239000011230 binding agent Substances 0.000 claims description 11
- 150000007530 organic bases Chemical class 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- 239000000314 lubricant Substances 0.000 claims description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 8
- 150000004677 hydrates Chemical class 0.000 claims description 8
- 239000012453 solvate Substances 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 7
- 229940090805 clavulanate Drugs 0.000 claims description 7
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims description 6
- 229960003324 clavulanic acid Drugs 0.000 claims description 6
- 239000003086 colorant Substances 0.000 claims description 6
- 239000000796 flavoring agent Substances 0.000 claims description 6
- 235000013355 food flavoring agent Nutrition 0.000 claims description 6
- 239000013078 crystal Substances 0.000 claims description 5
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 4
- 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 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 4
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 4
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 4
- 235000015165 citric acid Nutrition 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
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 229940069328 povidone Drugs 0.000 claims description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 4
- 238000011282 treatment Methods 0.000 claims description 4
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 4
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 2
- HXKKHQJGJAFBHI-UHFFFAOYSA-N 1-aminopropan-2-ol Chemical compound CC(O)CN HXKKHQJGJAFBHI-UHFFFAOYSA-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
- JHKKTXXMAQLGJB-UHFFFAOYSA-N 2-(methylamino)phenol Chemical compound CNC1=CC=CC=C1O JHKKTXXMAQLGJB-UHFFFAOYSA-N 0.000 claims description 2
- 229930186147 Cephalosporin Natural products 0.000 claims description 2
- UDIPTWFVPPPURJ-UHFFFAOYSA-M Cyclamate Chemical compound [Na+].[O-]S(=O)(=O)NC1CCCCC1 UDIPTWFVPPPURJ-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-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
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- 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
- 239000005715 Fructose Substances 0.000 claims description 2
- 229930091371 Fructose Natural products 0.000 claims description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 2
- 239000001828 Gelatine Substances 0.000 claims description 2
- 206010018612 Gonorrhoea Diseases 0.000 claims description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- 206010021531 Impetigo Diseases 0.000 claims description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 2
- 206010024971 Lower respiratory tract infections Diseases 0.000 claims description 2
- 208000016604 Lyme disease Diseases 0.000 claims description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 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
- FSVCELGFZIQNCK-UHFFFAOYSA-N N,N-bis(2-hydroxyethyl)glycine Chemical compound OCCN(CCO)CC(O)=O FSVCELGFZIQNCK-UHFFFAOYSA-N 0.000 claims description 2
- SEQKRHFRPICQDD-UHFFFAOYSA-N N-tris(hydroxymethyl)methylglycine Chemical compound OCC(CO)(CO)[NH2+]CC([O-])=O SEQKRHFRPICQDD-UHFFFAOYSA-N 0.000 claims description 2
- 206010033078 Otitis media Diseases 0.000 claims description 2
- 239000008118 PEG 6000 Substances 0.000 claims description 2
- 201000007100 Pharyngitis Diseases 0.000 claims description 2
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 2
- 206010037596 Pyelonephritis Diseases 0.000 claims description 2
- 208000006311 Pyoderma Diseases 0.000 claims description 2
- 206010057190 Respiratory tract infections Diseases 0.000 claims description 2
- 206010062255 Soft tissue infection Diseases 0.000 claims description 2
- 239000004376 Sucralose Substances 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- 206010046306 Upper respiratory tract infection Diseases 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
- YGCFIWIQZPHFLU-UHFFFAOYSA-N acesulfame Chemical compound CC1=CC(=O)NS(=O)(=O)O1 YGCFIWIQZPHFLU-UHFFFAOYSA-N 0.000 claims description 2
- 229960005164 acesulfame Drugs 0.000 claims description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
- 150000001412 amines Chemical class 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
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 2
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- FSBVERYRVPGNGG-UHFFFAOYSA-N dimagnesium dioxido-bis[[oxido(oxo)silyl]oxy]silane hydrate Chemical compound O.[Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O FSBVERYRVPGNGG-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 239000007911 effervescent powder Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229940099273 magnesium trisilicate Drugs 0.000 description 1
- 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
- 235000019793 magnesium trisilicate Nutrition 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229920003124 powdered cellulose Polymers 0.000 description 1
- 235000019814 powdered cellulose Nutrition 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
-
- 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
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0007—Effervescent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
Definitions
- Present invention is related to a process for use in the preparation of effervescent forms comprising cefdinir as active agent and the pharmaceutical formulations obtained by this process.
- Cefdinir molecule which is shown with Formula I was first disclosed in the patent numbered BE897864 and its chemical name is (6R,7R)-7-[[(2Z)-(2-amino-4- thiazolil)(hydroxyimino)acetyl] amino]-3-ethenyl-8-oxo-5-thia- 1 -azabicyclo[4.2.0]oct-2-en-2- carboxylic acid.
- the molecule which is a third generation cephalosporin, is indicated for the treatment of several illnesses caused by gram positive and gram negative bacteria.
- Cefdinir which physically appears as a white powder has very poor solubility in common organic solvents such as methanol, ethanol, and acetonitrile and in water. Due to this property there are some problems while developing effervescent formulations comprising this molecule.
- the difficulties encountered during the preparation of the formulation causes the problems in the physical properties of the final product, for instance the hardness and dispersion time parameters, or dose uniformity. This leads to some disadvantages for use of the patient and results in some problems about the bioavailability data since final product does not have dose uniformity.
- the present invention is related to granulating cefdinir with an aqueous solution of organic base in a method for use in the preparation of effervescent formulation comprising cefdinir.
- the present invention is related to the use of a production method comprising following the steps given below in the production of cefdinir formulations in the effervescent form. Therefore, said process comprises the following steps;
- a granulation solution comprising water in an amount of 80-98% of the total water amount to be used in the process and organic basic agent is prepared, (first granulation solution)
- a granulation solution comprising water in an amount of 2-20% of the total water amount to be used in the process, ethanol and binding agent is prepared, (second granulation solution)
- step III The granules obtained in step III are mixed with effervescent acid and sweetener and granulated with the second granulation solution,
- Said granules are mixed with lubricant, flavoring agent, sweetener and coloring agent,
- granulation of cefdinir with aqueous granulation solution comprising organic base prevents the agglomeration of this substance upon contact with water and this way dose uniformity of the final product was provided.
- one aspect of the invention is the use of the process described above in the production of the effervescent compositions comprising cefdinir.
- the effervescent formulation produced in accordance with the process of the present invention can be stored in tablet and/or sachet form.
- Organic basic agent to be used in the present invention can be selected from primary, secondary, tertiary organic amines comprising at least one hydroxyl group (-OH) and/or heterocyclic compounds comprising nitrogen.
- Organic base that can be used in the formulation can be selected from a group comprising ethanolamine, isopropanolamine, 1-deoxy-l-methylamino-sorbitol, 1-deoxy-l-methylamino-D- glucitol, tris(hydroxymethyl)aminomethane, N-(tri(hydroxymethyl)methyl)glycine, N,N-Bis(2- hydroxyethyl)glycine, 2-methyl aminophenol.
- 1-deoxy-l-methylamino-sorbitol and tris(hydroxymethyl)aminomethane are used.
- Cefdinir which can be used in effervescent powder, tablet and granule formulations of the present invention can be present in the form of its solvates, hydrates, enetiomers, racemates, organic salts, inorganic salts, polymorphs, crystal and amorphous forms or in free form and/or as a combination of these.
- Water which is used as a granulation solution in the present invention, is in the deionized form.
- Water amount to be used in first granulation solution is in the range of 80- 98% of the water amount to be used in the process, preferably in the range of 85-96%.
- Water amount to be used in second granulation solution is in the range of 2- 20% of the water amount to be used in the process, preferably in the range of 4-15%.
- Binder which can be used in the effervescent formulation that is produced by using the process in accordance with the present invention, can be selected from, but not limited with, a group comprising ethyl cellulose, gelatine, hydroxy ethyl cellulose, hydroxy methyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminium silicate, methyl cellulose, povidone. Preferably povidone is used.
- Lubricant which can be used in the effervescent formulation that is produced by using the process in accordance with the present invention, can be selected from, but not limited with, a group comprising calcium stearate, magnesium stearate, polyethylene glycol, PEG6000, polyvinyl alcohol, potassium benzoate, sodium benzoate.
- Sweetener which can be used in the effervescent formulation that is produced by using the process in accordance with the present invention, can be selected from, but not limited with, a group comprising acesulfame, aspartamate, dextrose, fructose, glucose, lactitol, maltitol, maltose, sorbitol, saccharide, sodium saccharide, sodium cyclamate, sucralose, sodium chloride, potassium chloride, sucrose, xylitol or combinations thereof.
- Sweetener which can be used in the steps IV and VI of the described process, can be selected from the above group and also they can be same or different from each other.
- Effervescent acid which will used in the effervescent formulation that is produced by using the process in accordance with the present invention, can be selected from organic acids such as citric acid, tartaric acid, malic acid, furmaric acid and effervescent base can be selected from basic agents such as sodium carbonate, sodium hydrogen carbonate, potassium carbonate and potassium hydrogen carbonate.
- effervescent formulation produced by the process in accordance with the present invention 1 -4000 mg of cefdinir or its pharmaceutically acceptable salts, hydrates, solvates or a combination thereof in an amount equivalent to that can be used.
- a second active agent can optionally be used.
- a second active agent can be selected from cefalosporins and beta-lactamase, preferably clavulanic acid or derivatives thereof is used.
- clavulanic acid which can optionally be used, is used in the form of its solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystal/amorphous forms or free form or in a combination thereof.
- potassium clavulanate is used.
- cefdinir formulation produced by the process in accordance with the present invention, optionally 50-500 mg of clavulanic acid or its pharmaceutically acceptable salts, hydrates, solvates or a combination thereof in an amount equivalent to that can be used.
- Clavulanic acid and derivatives thereof are very sensitive to moisture. Therefore, in the pharmaceutical composition in accordance with the present invention, preferably potasium clavulanate is used together with a desiccant in a ratio of 1 : 1.
- One or more than one of the following substances can be used as a desiccant; silica; colloidal silica, for instance colloidal silica anhydrous, Aerosil® 200, magnesium trisilicate, powdered cellulose, Cabosil®, magnesium oxide, calcium silicate, Syloid®, starch, microcrystalline cellulose and talc.
- silica colloidal silica, for instance colloidal silica anhydrous, Aerosil® 200, magnesium trisilicate, powdered cellulose, Cabosil®, magnesium oxide, calcium silicate, Syloid®, starch, microcrystalline cellulose and talc.
- potasium clavulanate is used together with syloid or microcrystalline cellulose in a ratio of 1 : 1.
- cefdinir formulation produced by the process in accordance with the present invention 5- 90%, preferably 10-80% of clavulanic acid in an amount by total weight of the unit dose or pharmaceutically acceptable salts, hydrates, solvates or a combination thereof in an amount equivalent to that can be used. Accordingly, in the cefdinir formulation produced by the process in accordance with the present invention, in cases where potasium clavulanate is used as the second active agent, said second active agent gets involved in the process in the steps II and/or IV and/or VI of the process.
- potasium clavulanate can be granuled with cefdinir by using the granulation solution comprising organic base or it can be mixed with the granules comprising cefdinir and organic base and granuled by using the granulation solution comprising binder or it can be mixed with the granules including cefdinir dryly.
- Effervescent formulations in accordance with the present invention can be prepared according to the following examples provided that they are not limited by these examples, P T/TR2010/000257
- EXAMPLE 1 Formulation and process for the preparation of effervescent tablet
- Formulation to be prepared in accordance with the present invention is obtained by granulation of sodium hydrogen carbonate and cefdinir with aqueous solution of organic base and then mixing the formed granules with citric acid and sweetener. The formed mixture is then granulated with a solution of binder. The granule obtained after this step is mixed with lubricant, coloring agent, sweetener and flavouring agent and preferably it is compressed in the form of tablets.
- EXAMPLE 2 Formulation and process for the preparation of effervescent tablet
- Formulation can be obtained by granulation of cefdinir with aqueous solution of organic base and then mixing the formed granules with sweetener, effervescent acid and potassium clavulanate:syloid. The formed mixture is then granulated with a solution of binder. The granule obtained after this step is mixed with lubricant, coloring agent, sweetener and flavouring agent and optionally it can be pressed as tablets.
- present invention relates to use of effervescent formulations comprising cefdinir and in addition to that pharmaceutically acceptable excipients for the treatment of infections caused by gram positive and gram negative bacteria.
- pharmaceutical formulation prepared in accordance with the present invention is used in the production of the drug to be used in the treatment and prophylaxis of upper respiratory tract infections such that ear, nose, throat, otitis media, sinusitis, tonsillitis, pharyngitis, lower respiratory tract infections such as pyelonephritis, cystitis and urethritis, skin and soft tissue infections such as froncle, pyoderma, impetigo and also gonorrhea and lyme diseases.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cephalosporin Compounds (AREA)
Abstract
Present invention is related to processes that are used in the preparation of effervescent form comprising cefdinir as active agent and the pharmaceutical formulations obtained by this process.
Description
THE PRODUCTION METHOD FOR EFFERVESCENT TABLET WITH
CEFDINIR
Present invention is related to a process for use in the preparation of effervescent forms comprising cefdinir as active agent and the pharmaceutical formulations obtained by this process. Background of the invention
Cefdinir molecule which is shown with Formula I was first disclosed in the patent numbered BE897864 and its chemical name is (6R,7R)-7-[[(2Z)-(2-amino-4- thiazolil)(hydroxyimino)acetyl] amino]-3-ethenyl-8-oxo-5-thia- 1 -azabicyclo[4.2.0]oct-2-en-2- carboxylic acid. The molecule which is a third generation cephalosporin, is indicated for the treatment of several illnesses caused by gram positive and gram negative bacteria.
Formula I
Cefdinir which physically appears as a white powder has very poor solubility in common organic solvents such as methanol, ethanol, and acetonitrile and in water. Due to this property there are some problems while developing effervescent formulations comprising this molecule. The difficulties encountered during the preparation of the formulation causes the problems in the physical properties of the final product, for instance the hardness and dispersion time parameters, or dose uniformity. This leads to some disadvantages for use of the patient and results in some problems about the bioavailability data since final product does not have dose uniformity.
The production processes in which the components are blended by dry granulation and/or blending method are preferred in order to prevent the problems resulting from solubility of cefdinir in the process. However, it is observed that pharmaceutical composition prepared by said process fails to satisfy the desired tablet hardness when the formulation prepared is compressed in a tablet form.
One of the problems frequently confronted in developing the formulations is that in the processes including wet granulation method once the active agent contacts with water, it is agglomerated
due to its hydrophobic character and due to this reason, dose uniformity of the final product can not be provided.
In view of the prior art, it is seen that new processes for use in the preparation of formulations of effervescent compositions comprising cefdinir, wherein said composition is stable, has long shelf life and high bio-availability, are required.
The inventors have surprisingly found that the problems confronted in the prior art can be solved by using the process in accordance with the invention in the preparation of cefdinir formulations in effervescent form
Detailed Description of the Invention
The present invention is related to granulating cefdinir with an aqueous solution of organic base in a method for use in the preparation of effervescent formulation comprising cefdinir.
In another aspect, the present invention is related to the use of a production method comprising following the steps given below in the production of cefdinir formulations in the effervescent form. Therefore, said process comprises the following steps;
I. A granulation solution comprising water in an amount of 80-98% of the total water amount to be used in the process and organic basic agent is prepared, (first granulation solution)
II. Effervescent base and cefdinir are granulated with this granulation solution, (first granulation)
III. A granulation solution comprising water in an amount of 2-20% of the total water amount to be used in the process, ethanol and binding agent is prepared, (second granulation solution)
IV. The granules obtained in step III are mixed with effervescent acid and sweetener and granulated with the second granulation solution,
V. The granules obtained are dried and screened,
VI. Said granules are mixed with lubricant, flavoring agent, sweetener and coloring agent,
VII. The obtained composition is stored in accordance with the desired dosage form.
0257
In the process in accordance with the invention, granulation of cefdinir with aqueous granulation solution comprising organic base prevents the agglomeration of this substance upon contact with water and this way dose uniformity of the final product was provided.
Accordingly, one aspect of the invention is the use of the process described above in the production of the effervescent compositions comprising cefdinir.
The effervescent formulation produced in accordance with the process of the present invention can be stored in tablet and/or sachet form.
Organic basic agent to be used in the present invention can be selected from primary, secondary, tertiary organic amines comprising at least one hydroxyl group (-OH) and/or heterocyclic compounds comprising nitrogen.
Organic base that can be used in the formulation can be selected from a group comprising ethanolamine, isopropanolamine, 1-deoxy-l-methylamino-sorbitol, 1-deoxy-l-methylamino-D- glucitol, tris(hydroxymethyl)aminomethane, N-(tri(hydroxymethyl)methyl)glycine, N,N-Bis(2- hydroxyethyl)glycine, 2-methyl aminophenol. Preferably 1-deoxy-l-methylamino-sorbitol and tris(hydroxymethyl)aminomethane are used.
Cefdinir which can be used in effervescent powder, tablet and granule formulations of the present invention can be present in the form of its solvates, hydrates, enetiomers, racemates, organic salts, inorganic salts, polymorphs, crystal and amorphous forms or in free form and/or as a combination of these. Water, which is used as a granulation solution in the present invention, is in the deionized form.
Water amount to be used in first granulation solution is in the range of 80- 98% of the water amount to be used in the process, preferably in the range of 85-96%. Water amount to be used in second granulation solution is in the range of 2- 20% of the water amount to be used in the process, preferably in the range of 4-15%. Binder, which can be used in the effervescent formulation that is produced by using the process in accordance with the present invention, can be selected from, but not limited with, a group comprising ethyl cellulose, gelatine, hydroxy ethyl cellulose, hydroxy methyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminium silicate, methyl cellulose, povidone. Preferably povidone is used.
Lubricant, which can be used in the effervescent formulation that is produced by using the process in accordance with the present invention, can be selected from, but not limited with, a group comprising calcium stearate, magnesium stearate, polyethylene glycol, PEG6000, polyvinyl alcohol, potassium benzoate, sodium benzoate. Sweetener, which can be used in the effervescent formulation that is produced by using the process in accordance with the present invention, can be selected from, but not limited with, a group comprising acesulfame, aspartamate, dextrose, fructose, glucose, lactitol, maltitol, maltose, sorbitol, saccharide, sodium saccharide, sodium cyclamate, sucralose, sodium chloride, potassium chloride, sucrose, xylitol or combinations thereof. Sweetener, which can be used in the steps IV and VI of the described process, can be selected from the above group and also they can be same or different from each other.
Effervescent acid, which will used in the effervescent formulation that is produced by using the process in accordance with the present invention, can be selected from organic acids such as citric acid, tartaric acid, malic acid, furmaric acid and effervescent base can be selected from basic agents such as sodium carbonate, sodium hydrogen carbonate, potassium carbonate and potassium hydrogen carbonate.
In the effervescent formulation produced by the process in accordance with the present invention, 1 -4000 mg of cefdinir or its pharmaceutically acceptable salts, hydrates, solvates or a combination thereof in an amount equivalent to that can be used. In the effervescent formulation produced by the process in accordance with the present invention, 5-60% of cefdinir or pharmaceutically acceptable solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystal/amorphous forms, 1-30% organic base, 1-30% binder, 0.1-3 % lubricant, % 0.1-5% sweetener and/or taste regulating agent, 0.1- 8% coloring and/or flavoring agent and 0.1-90% effervescent couple in an amount with respect to the total weight of the unit dose can be used.
In the cefdinir formulation produced by the process in accordance with the present invention, a second active agent can optionally be used. A second active agent can be selected from cefalosporins and beta-lactamase, preferably clavulanic acid or derivatives thereof is used.
In the cefdinir formulation produced by the process in accordance with the present invention, clavulanic acid, which can optionally be used, is used in the form of its solvates, hydrates,
enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystal/amorphous forms or free form or in a combination thereof. Preferably potassium clavulanate is used.
In the cefdinir formulation produced by the process in accordance with the present invention, optionally 50-500 mg of clavulanic acid or its pharmaceutically acceptable salts, hydrates, solvates or a combination thereof in an amount equivalent to that can be used.
Clavulanic acid and derivatives thereof (for example potasium clavulanate) are very sensitive to moisture. Therefore, in the pharmaceutical composition in accordance with the present invention, preferably potasium clavulanate is used together with a desiccant in a ratio of 1 : 1.
One or more than one of the following substances can be used as a desiccant; silica; colloidal silica, for instance colloidal silica anhydrous, Aerosil® 200, magnesium trisilicate, powdered cellulose, Cabosil®, magnesium oxide, calcium silicate, Syloid®, starch, microcrystalline cellulose and talc.
In the cefdinir formulation produced by the process in accordance with the present invention, preferably potasium clavulanate is used together with syloid or microcrystalline cellulose in a ratio of 1 : 1.
In the cefdinir formulation produced by the process in accordance with the present invention, 5- 90%, preferably 10-80% of clavulanic acid in an amount by total weight of the unit dose or pharmaceutically acceptable salts, hydrates, solvates or a combination thereof in an amount equivalent to that can be used. Accordingly, in the cefdinir formulation produced by the process in accordance with the present invention, in cases where potasium clavulanate is used as the second active agent, said second active agent gets involved in the process in the steps II and/or IV and/or VI of the process.
In another aspect, potasium clavulanate can be granuled with cefdinir by using the granulation solution comprising organic base or it can be mixed with the granules comprising cefdinir and organic base and granuled by using the granulation solution comprising binder or it can be mixed with the granules including cefdinir dryly.
Effervescent formulations in accordance with the present invention can be prepared according to the following examples provided that they are not limited by these examples,
P T/TR2010/000257
EXAMPLE 1: Formulation and process for the preparation of effervescent tablet
Formulation to be prepared in accordance with the present invention is obtained by granulation of sodium hydrogen carbonate and cefdinir with aqueous solution of organic base and then mixing the formed granules with citric acid and sweetener. The formed mixture is then granulated with a solution of binder. The granule obtained after this step is mixed with lubricant, coloring agent, sweetener and flavouring agent and preferably it is compressed in the form of tablets.
EXAMPLE 2: Formulation and process for the preparation of effervescent tablet
% amount in unit dose
Cefdinir 20%
Potassium clavulanate:syloid 13%
Organic base 9%
Citric acid 30%
Sodium hydrogen carbonate 20%
Binder 2.5%
Sweetener 2.5%
Lubricant 0.75%
Formulation can be obtained by granulation of cefdinir with aqueous solution of organic base and then mixing the formed granules with sweetener, effervescent acid and potassium clavulanate:syloid. The formed mixture is then granulated with a solution of binder. The granule obtained after this step is mixed with lubricant, coloring agent, sweetener and flavouring agent and optionally it can be pressed as tablets.
In another aspect, present invention relates to use of effervescent formulations comprising cefdinir and in addition to that pharmaceutically acceptable excipients for the treatment of infections caused by gram positive and gram negative bacteria. In another aspect pharmaceutical formulation prepared in accordance with the present invention, is used in the production of the drug to be used in the treatment and prophylaxis of upper respiratory tract infections such that ear, nose, throat, otitis media, sinusitis, tonsillitis, pharyngitis, lower respiratory tract infections such as pyelonephritis, cystitis and urethritis, skin and soft tissue infections such as froncle, pyoderma, impetigo and also gonorrhea and lyme diseases.
Claims
1. A method for the preparation of the effervescent formulation comprising cefdinir, characterized in that cefdinir is granulated with an aqueous solution of organic basic compound.
2. A method for the preparation of the effervescent formulation comprising cefdinir according to claim 1, wherein said method comprises the following steps;
I. A granulation solution comprising organic basic agent and water in an amount of 80-98% of the total water amount that is used in the process is prepared, (first granulation solution)
II. Effervescent base and cefdinir are granulated with this granulation solution, (first granulation)
III. A granulation solution comprising water in an amount of 2-20% of the total water amount that is used in the process, ethanol and binding agent is prepared, (second granulation solution)
IV. The granules obtained are mixed with effervescent asid and sweetener and granuled with second granulation solution,
V. The granules obtained are dried and sieved,
VI. Said granules are mixed with lubricant, flavoring agent, sweetener and coloring agent, VII. The obtained composition is stored in accordance with the desired dosage form.
3. A process according to claims 1-2, wherein organic basic agent that is used is selected from primary, secondary, tertiary organic amines comprising at least one hydroxyl group (-OH) and/or heterocyclic compound comprising nitrogen.
4. A process according to claim 3, wherein organic basic agent that is used is selected from a group comprising ethanolamine, isopropanolamine, 1-deoxy-l-methylamino-sorbitol, 1- deoxy-l-methylamino-D-glucitol, tris(hydroxymethyl)aminomethane, N- (tri(hydroxymethyl)methyl)glycine, N,N-Bis(2-hydroxyethyl)glycine, 2-methyl aminophenol.
5. A process according to claims 4, wherein organic basic agent is 1-deoxy-l-methylamino- sorbitol and/or tris(hydroxymethyl)aminomethane.
6. A process according to claims 1-2, wherein water used as a granulation solution in the present invention is in the deionized form.
7. A process according to claim 2, wherein water amount to be used in first granulation solution is in the range of 80- 98% with respect to the total amount of water that is used in the process.
8. A process according to claim 7, wherein water amount to be used in first granulation solution is in the range of 85- 96% with respect to the total amount of water that is used in the process.
9. A process according to claim 2, wherein water amount to be used in second granulation solution is in the range of 2- 20% with respect to the total amount of water that is used in the process..
10. A process according to claim 9, wherein water amount to be used in second granulation solution is in the range of 4- 15% with respect to the total amount of water that is used in the process.
11. Cefdinir, that will be used in the formulation prepared according to the process, according to claims 1-2, is present in the form of its solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystal and amorphous forms or in free form and/or as a combination of these.
12. Binder, that will be used in the formulation prepared according to the process, according to claims 1-2, is selected from a group comprising ethyl cellulose, gelatine, hydroxy ethyl cellulose, hydroxy methyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium alumimum silicate, methyl cellulose, povidone.
13. A formulation according to claim 12, wherein in said formulation povidone is used as a binder.
14. Lubricant, that will be used in the formulation prepared according to the process, according to claims 1-2, is selected from a group comprising calcium stearate, magnesium stearate, polyethylene glycol, PEG6000, polyvinyl alcohol, potassium benzoate, sodium benzoate.
15. Sweetener, that will be used in the formulation prepared according to the process, according to claims 1-2, is selected from a group comprising acesulfame, aspartamate, dextrose, fructose, glucose, lactitol, maltitol, maltose, sorbitol, saccharide, sodium saccharide, sodium cyclamate, sucralose, sodium chloride, potassium chloride, sucrose, xylitol or combinations thereof.
16. A process according to claims 1-2, wherein sweetener used in the steps IV and VI of said process can be same or different from each other.
17. Effervescent acid, that will be used in the formulation prepared according to the process, according to claims 1-2, is selected from organic acids such as citric acid, tartaric acid, malic acid, furmaric acid and effervescent base is selected from basic agents such as sodium carbonate, sodium hydrogen carbonate, potassium carbonate and potassium hydrogen carbonate.
18. A formulation prepared according to the process disclosed in claims 1 and 2, wherein with respect to the total weight of the unit dose;
• 5-60% of cefdinir or pharmaceutically acceptable solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystal and amorphous forms, · 1-30% organic base,
• 1-30% binder
• 0.1-3 % lubricant
• % 0.1 -5% sweetener
• 0.1-8 % coloring and/or flavouring agent
· 0.1-90% effervescent couple is used.
19. A formulation prepared according to the process disclosed in claims 1 and 2, wherein in said formulation may further comprise a second active agent selected from cephalosporins and beta-lactemase.
20. A formulation according to claim 19, wherein as the second active agent clavulanic acid, preferably potasium clavulanate is used.
21. A formulation according to claim 20, wherein potasium clavulanate is added in II and/or IV and/or VI steps of the process described in claim 2.
22. A formulation prepared according to the process described in claims 1 and 2, wherein said formulation is used for the manufacture of a medicament for use in the treatment and prophylaxis of upper respiratory tract infections such that ear, nose, throat, otitis media, sinusitis, tonsillitis, pharyngitis, lower respiratory tract infections such as pyelonephritis, cystitis and urethritis, skin and soft tissue infections such as froncle, pyoderma, impetigo and also gonorrhea and lyme diseases.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2009/09785A TR200909785A1 (en) | 2009-12-25 | 2009-12-25 | Pharmaceutical compositions containing cefdinir as the active agent. |
| PCT/TR2010/000257 WO2011078827A1 (en) | 2009-12-25 | 2010-12-24 | The production method for effervescent tablet with cefdinir |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP2515857A1 true EP2515857A1 (en) | 2012-10-31 |
Family
ID=43513728
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP10795487.7A Active EP2515850B1 (en) | 2009-12-25 | 2010-12-03 | Pharmaceutical compositions comprising cefdinir as an active agent |
| EP10807505A Withdrawn EP2515862A1 (en) | 2009-12-25 | 2010-12-24 | Rapidly dispersing pharmaceutical formulation with cefdinir |
| EP10805667.2A Active EP2515860B1 (en) | 2009-12-25 | 2010-12-24 | Improved pharmaceutical compositions comprising cefdinir |
| EP10805546A Withdrawn EP2515857A1 (en) | 2009-12-25 | 2010-12-24 | The production method for effervescent tablet with cefdinir |
Family Applications Before (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP10795487.7A Active EP2515850B1 (en) | 2009-12-25 | 2010-12-03 | Pharmaceutical compositions comprising cefdinir as an active agent |
| EP10807505A Withdrawn EP2515862A1 (en) | 2009-12-25 | 2010-12-24 | Rapidly dispersing pharmaceutical formulation with cefdinir |
| EP10805667.2A Active EP2515860B1 (en) | 2009-12-25 | 2010-12-24 | Improved pharmaceutical compositions comprising cefdinir |
Country Status (3)
| Country | Link |
|---|---|
| EP (4) | EP2515850B1 (en) |
| TR (1) | TR200909785A1 (en) |
| WO (4) | WO2011078822A1 (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TR201010859A2 (en) * | 2010-11-05 | 2012-05-21 | Bi̇lgi̇ç Mahmut | Tablet forms containing cefdinir. |
| TR201010212A2 (en) * | 2010-12-08 | 2012-06-21 | Bi̇lgi̇ç Mahmut | Solid oral dosage form containing cefdinir. |
| WO2013095313A1 (en) * | 2011-12-19 | 2013-06-27 | Mahmut Bilgic | Pharmaceutical formulations comprising cefdinir |
| CN103637992B (en) * | 2013-12-19 | 2015-04-08 | 石家庄市华新药业有限责任公司 | Cefdinir granular preparation and preparation method thereof |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA836918B (en) | 1982-09-30 | 1984-05-30 | Fujisawa Pharmaceutical Co | 7-substituted-3-vinyl-3-cephem compounds and processes for the production of the same |
| ATE216887T1 (en) * | 1996-02-29 | 2002-05-15 | Fujisawa Pharmaceutical Co | TABLETS CONTAINING BETA-LACTAM ANTIBIOTIC AND METHOD FOR THE PRODUCTION THEREOF |
| WO2004104010A1 (en) * | 2003-05-20 | 2004-12-02 | Ranbaxy Laboratories Limited | Crystalline form of cefdinir |
| US20050131079A1 (en) * | 2003-12-10 | 2005-06-16 | Pujara Chetan P. | Cefdinir oral suspension |
| WO2006106529A1 (en) * | 2005-04-05 | 2006-10-12 | Lupin Limited | A co-spray dried composition of cefepime with base and process for preparation thereof |
| CN1706389A (en) * | 2005-05-26 | 2005-12-14 | 济南平志医药科技有限公司 | Effervescent cefdinir prepn and its prepn process |
| US20070128268A1 (en) * | 2005-12-07 | 2007-06-07 | Herwig Jennewein | Pharmaceutical compositions comprising an antibiotic |
| US20090275552A1 (en) * | 2006-04-28 | 2009-11-05 | Mahesh Vithalbhai Patel | Therapy for Treating Resistant Bacterial Infections |
| US20080103124A1 (en) * | 2006-10-25 | 2008-05-01 | Astellas Pharma Inc. | Cefdinir-containing pharmaceutical composition |
| DE102007002924A1 (en) * | 2007-01-19 | 2008-07-24 | Bayer Healthcare Ag | ß-lactam-containing formulations with increased stability in aqueous solution |
| CN101352424A (en) * | 2008-09-16 | 2009-01-28 | 天津市中央药业有限公司 | Cefdinir dispersible tablet and preparation method thereof |
-
2009
- 2009-12-25 TR TR2009/09785A patent/TR200909785A1/en unknown
-
2010
- 2010-12-03 EP EP10795487.7A patent/EP2515850B1/en active Active
- 2010-12-03 WO PCT/TR2010/000242 patent/WO2011078822A1/en not_active Ceased
- 2010-12-24 EP EP10807505A patent/EP2515862A1/en not_active Withdrawn
- 2010-12-24 WO PCT/TR2010/000257 patent/WO2011078827A1/en not_active Ceased
- 2010-12-24 WO PCT/TR2010/000261 patent/WO2011078831A1/en not_active Ceased
- 2010-12-24 WO PCT/TR2010/000259 patent/WO2011078829A1/en not_active Ceased
- 2010-12-24 EP EP10805667.2A patent/EP2515860B1/en active Active
- 2010-12-24 EP EP10805546A patent/EP2515857A1/en not_active Withdrawn
Non-Patent Citations (2)
| Title |
|---|
| MARTIN M A ET AL: "INCREASE IN THE ACTIVITY OF THIRD-GENERATION CEPHALOSPORINS IN COMBINATION WITH CLAVULANIC ACID AND SULBACTAM AGAINST BACTEROIDES-FRAGILIS", MEDICAL LABORATORY SCIENCES, ACADEMIC PRESS, LONDON, GB, vol. 47, no. 3, 1 January 1990 (1990-01-01), pages 163 - 167, XP008133356, ISSN: 0308-3616 * |
| See also references of WO2011078827A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2011078827A1 (en) | 2011-06-30 |
| EP2515850A1 (en) | 2012-10-31 |
| EP2515860B1 (en) | 2015-07-29 |
| TR200909785A1 (en) | 2011-07-21 |
| EP2515850B1 (en) | 2016-06-29 |
| WO2011078829A1 (en) | 2011-06-30 |
| EP2515862A1 (en) | 2012-10-31 |
| EP2515860A1 (en) | 2012-10-31 |
| WO2011078831A1 (en) | 2011-06-30 |
| WO2011078822A1 (en) | 2011-06-30 |
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