WO2011152808A1 - Formulation comprising cefpodoxime proxetil and clavulanic acid - Google Patents
Formulation comprising cefpodoxime proxetil and clavulanic acid Download PDFInfo
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- WO2011152808A1 WO2011152808A1 PCT/TR2011/000148 TR2011000148W WO2011152808A1 WO 2011152808 A1 WO2011152808 A1 WO 2011152808A1 TR 2011000148 W TR2011000148 W TR 2011000148W WO 2011152808 A1 WO2011152808 A1 WO 2011152808A1
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- Prior art keywords
- pharmaceutical composition
- composition according
- clavulanic acid
- microcrystalline cellulose
- cefpodoxime proxetil
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
- A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
Definitions
- the present invention relates to pharmaceutical compositions comprising cefpodoxime proxetil and clavulanic acid and/or derivatives thereof as the active agents.
- Cefpodoxime proxetil (Formula I), chemical name of which is pivaloyloxymethyl 7-[2-(2- amino-thiazole-4-yl]-2-(syn)-methoxyimino-acetamido]-3-methoxymethyl-3-cefem-4- carboxylate, was first disclosed in the patent numbered EP0049118.
- Clavulanic acid is a beta-lactamase inhibitor illustrated in Formula 2.
- Clavulanic acid and derivatives thereof are known as the beta-lactamase inhibitors which withstand the beta-lactamase-originated resistance mechanism by suppressing the activity of beta-lactamase enzymes.
- EP0593573 comprises a formulation relating to suspension forms of beta-lactam antibiotics and beta lactamase inhibitors.
- suspension forms are not preferred much as they have the potential of high and/or uncontrolled dose intake; there appear problems in their physical and chemical stability; they have high manufacture costs and they cause problems in use and carrying.
- the inventors have aimed to develop stable oral pharmaceutical formulations which comprise cefpodoxime proxetil and clavulanic acid derivatives thereof together and eliminate the low solubility problem of cefpodoxime proxetil.
- the present invention relates to stable pharmaceutical compositions with good solubility characteristics in which cefpodoxime proxetil and clavulanic acid are formulated together. It has surprisingly been seen that when the pharmaceutical composition comprising cefpodoxime proxetil and clavulanic acid wherein
- each one of the cellulose-based disintegrants is present in an amount more than 7% by weight with respect to the weight of the unit dose is developed, dissolution of the cefpodoxime proxetil increases and dissolution time of the composition decreases.
- the first aspect of the present invention is the pharmaceutical compositions comprising cefpodoxime proxetil and clavulanic acid as the active agents wherein a combination of croscarmellose and microcrystalline cellulose is used as the disintegrant and each one of the cellulose-based disintegrants is present in an amount more than 7% with respect to the unit dose.
- Cefpodoxime proxetil that can be used in the pharmaceutical composition of the present invention can be in the form of its solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms or in free base form and/or a combination thereof.
- Clavulanic acid that can be used in the pharmaceutical composition of the present invention can be in the form of its solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms or free base form and/or a combination thereof.
- potassium clavulanate is used in the present invention.
- Croscarmellose sodium used in the pharmaceutical composition according to the present invention is present in an amount more than 7%, preferably in the range of 8-15%, more preferably in the range of 9-12% with respect to unit dose amount. Although the use of croscarmellose sodium in this specified amount is more than the amount disclosed in the prior art, the inventors have found that the dissolution rate of the composition increases in contrast to expectations.
- compositions comprising cefpodoxime proxetil and clavulanic acid or its derivatives wherein croscarmellose sodium is preferably used in an amount in the range of 8-15%, more preferably in an amount in the range of 9-12% by weight with respect to the weight of the unit dose.
- Microcrystalline cellulose used in the pharmaceutical composition according to the present invention is present in an amount more than 7%, preferably in the range of 8-15%, more preferably in the range of 9-13% with respect to unit dose amount.
- the inventors have found that the dissolution time reduces by 60% in the case that microcrystalline cellulose is used in said amount.
- compositions comprising cefpodoxime proxetil and clavulanic acid or its derivatives wherein microcrystalline cellulose is preferably used in an amount in the range of 8-15%, more preferably in an amount in the range of 9-13% by weight with respect to the weight of the unit dose.
- each cellulose-based disintegrant in an amount more than 7% with respect to the unit dose has an important effect on both the increase of dissolution of cefpodoxime proxetil and decrease in dissolution time of the composition comprising cefpodoxime proxetil and clavulanic acid.
- the inventors have observed that an optimum particle size of the cellulose-based disintegrant used in the composition of the present invention has a considerable effect on the disintegration and dissolution of the composition. They have found that when the particle size of microcrystalline cellulose used in the present invention is less than 100 ⁇ , preferably in the range of 30-90 ⁇ and more preferably in the range of 40-60 ⁇ , the dissolution of the composition increases and also dissolution time decreases.
- compositions comprising cefpodoxime proxetil and clavulanic acid or its derivatives wherein microcrystalline cellulose with a particle size less than 100 ⁇ , preferably in the range of 30- 90 ⁇ and more preferably in the range of 40-60 ⁇ is used in the disintegrant combination.
- the formulation of the present invention can comprise various excipients such as, but not limited to, glidants, lubricants, diluents, surfactants and optionally coating agents.
- the glidant that can be used in the pharmaceutical composition of the present invention can be selected from, but not limited to, a group comprising magnesium silicate, silicon dioxide, starch, talc, tribasic calcium phosphate or combinations thereof.
- the lubricant that can be used in the pharmaceutical composition of the present invention can be selected from, but not limited to, a group comprising calcium stearate, magnesium stearate, polyoxyethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, talc, sodium benzoate or combinations thereof.
- magnesium stearate is used as the lubricant in the pharmaceutical composition of the present invention.
- the diluent that can be used in the pharmaceutical composition of the present invention can be selected from, but not limited to, a group comprising calcium carbonate, calcium sulfate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, microcrystalline cellulose, lactose, magnesium carbonate, magnesium oxide, maltodextrin, maltose, mannitol, sodium chloride, sorbitol, starch, xylitol or combinations thereof.
- the surfactant that can be used in the pharmaceutical composition of the present invention can be selected from, but not limited to, a group comprising docusate sodium, sorbitan esters, cetrimide and sodium lauryl sulfate.
- sodium lauryl sulfate is preferably used as the surfactant.
- the pharmaceutical composition of the present invention can comprise 20-800 mg cefpodoxime proxetil or its pharmaceutically acceptable salts, hydrates, solvates or combinations thereof in an equal amount.
- the pharmaceutical composition of the present invention can comprise 50-500 mg clavulanic acid or its pharmaceutically acceptable salts, hydrates, solvates or combinations thereof in an equal amount.
- Clavulanic acid and its derivatives e.g. potassium clavulanate
- potassium clavulanate in the pharmaceutical composition is preferably used with a humectant in the ratio of 1 : 1.
- colloidal silica for instance colloidal silica anhydrous, for example Aerosil® 200, magnesium trisilicate, cellulose powder, Cabosil®, magnesium oxide, calcium silicate, Syloid®, starch, microcrystalline cellulose, talc can be used as the humectant.
- potassium clavulanate is used with microcrystalline cellulose preferably in the ratio of 1 : 1.
- the pharmaceutical composition of the present invention can comprise 5-60% cefpodoxime proxetil in proportion to total weight of unit dose or pharmaceutically acceptable solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms thereof.
- the pharmaceutical composition of the present invention can comprise 5-50% clavulanic acid in proportion to total weight of unit dose or pharmaceutically acceptable salts, hydrates, solvates or combinations thereof in an equal amount.
- the pharmaceutical composition of the present invention can comprise 5-60% cefpodoxime proxetil; 5-50% potassium clavulanate; 0,5-5% glidant; 0,1-5% lubricant; 0,1-25% disintegrant and/or disintegrants; 1-30% diluent; 0,1-5% surfactant and optionally coating agent of 1-5% of the core weight.
- the pharmaceutical composition comprising cefpodoxime proxetil and clavulanic acid prepared according to the present invention can be in conventional tablet, film coated tablet, sachet or capsule form.
- the present invention relates to processes for preparation of pharmaceutical compositions comprising pharmaceutically acceptable excipients in addition to cefpodoxime proxetil and clavulanic acid or its derivatives as the active agents.
- the process of the present invention comprises the steps of granulating the active agent cefpodoxime proxetil and clavulanic acid or its derivatives by conventional wet and/or dry granulation methods; or powdering cefpodoxime proxetil, clavulanic acid derivatives and other excipients after mixing them by dry blending method and - compressing the pharmaceutical composition of the present invention in tablet form and optionally coating the tablets with a coating agent in the case that the product is developed in tablet form and/or,
- Another aspect of the present invention is that the formulation prepared according to said invention is used in the treatment of diseases related with infections caused by gram negative and gram positive bacteria.
- the pharmaceutical composition prepared according to the present invention is used in the production of a medicament so as to be used in upper respiratory infections such as ear, nose, throat, otitis media, sinusitis, tonsillitis, pharyngitis; lower respiratory tract infections such as pyelonephritis, cystitis and urethritis; skin or soft tissue infections such as froncle, pyoderma, impetigo; in the treatment and prophylaxis of gonorrhea and lyme diseases.
- upper respiratory infections such as ear, nose, throat, otitis media, sinusitis, tonsillitis, pharyngitis
- lower respiratory tract infections such as pyelonephritis, cystitis and urethritis
- skin or soft tissue infections such as froncle, pyoderma, impetigo
- in the treatment and prophylaxis of gonorrhea and lyme diseases in the production of a medicament so as to be used in upper respiratory infections such as
- composition of the present invention can be prepared as described below, but not limited to the examples given.
- EXAMPLE 1 Formulation and process for preparation of film tablet comprising cefpodoxime proxetil and potasium clavulanate
- a process for preparation of pharmaceutical compositions is composed of the steps of mixing and compressing cefpodoxime proxetil, the disintegrant and the diluent and then sieving them; adding the surfactant, potassium clavulanate: avicel, disintegrant, glidant and lubricant into the granules obtained and mixing them; and then compressing tablets of the mixture obtained and coating the tablets with coating material.
Abstract
The present invention relates to pharmaceutical compositions comprising cefpodoxime proxetil and clavulanic acid and/or its derivatives as the active agents.
Description
FORMULATION COMPRISING CEFPODOXIME PROXETIL AND CLAVULANIC
ACID
The present invention relates to pharmaceutical compositions comprising cefpodoxime proxetil and clavulanic acid and/or derivatives thereof as the active agents.
Background of the Invention
Cefpodoxime proxetil (Formula I), chemical name of which is pivaloyloxymethyl 7-[2-(2- amino-thiazole-4-yl]-2-(syn)-methoxyimino-acetamido]-3-methoxymethyl-3-cefem-4- carboxylate, was first disclosed in the patent numbered EP0049118.
Formula 1
Clavulanic acid, on the other hand, is a beta-lactamase inhibitor illustrated in Formula 2.
Formula 2
Clavulanic acid and derivatives thereof (for instance its salts such as potassium clavulanate) are known as the beta-lactamase inhibitors which withstand the beta-lactamase-originated resistance mechanism by suppressing the activity of beta-lactamase enzymes.
The patent numbered EP0593573 comprises a formulation relating to suspension forms of beta-lactam antibiotics and beta lactamase inhibitors.
However, suspension forms are not preferred much as they have the potential of high and/or uncontrolled dose intake; there appear problems in their physical and chemical stability; they have high manufacture costs and they cause problems in use and carrying.
To this end, the inventors have aimed to develop stable oral pharmaceutical formulations which comprise cefpodoxime proxetil and clavulanic acid derivatives thereof together and eliminate the low solubility problem of cefpodoxime proxetil.
Description of the Invention:
The present invention relates to stable pharmaceutical compositions with good solubility characteristics in which cefpodoxime proxetil and clavulanic acid are formulated together. It has surprisingly been seen that when the pharmaceutical composition comprising cefpodoxime proxetil and clavulanic acid wherein
- a combination of croscarmellose sodium and microcrystalline cellulose is used as the disintegrant and
- each one of the cellulose-based disintegrants is present in an amount more than 7% by weight with respect to the weight of the unit dose is developed, dissolution of the cefpodoxime proxetil increases and dissolution time of the composition decreases.
According to this, the first aspect of the present invention is the pharmaceutical compositions comprising cefpodoxime proxetil and clavulanic acid as the active agents wherein a combination of croscarmellose and microcrystalline cellulose is used as the disintegrant and each one of the cellulose-based disintegrants is present in an amount more than 7% with respect to the unit dose.
Cefpodoxime proxetil that can be used in the pharmaceutical composition of the present invention can be in the form of its solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms or in free base form and/or a combination thereof.
Clavulanic acid that can be used in the pharmaceutical composition of the present invention can be in the form of its solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms or free base form and/or a combination thereof. Preferably, potassium clavulanate is used in the present invention.
Croscarmellose sodium used in the pharmaceutical composition according to the present invention is present in an amount more than 7%, preferably in the range of 8-15%, more preferably in the range of 9-12% with respect to unit dose amount. Although the use of croscarmellose sodium in this specified amount is more than the amount disclosed in the prior art, the inventors have found that the dissolution rate of the composition increases in contrast to expectations.
Another aspect of the present invention is the pharmaceutical compositions comprising cefpodoxime proxetil and clavulanic acid or its derivatives wherein croscarmellose sodium is preferably used in an amount in the range of 8-15%, more preferably in an amount in the range of 9-12% by weight with respect to the weight of the unit dose.
Microcrystalline cellulose used in the pharmaceutical composition according to the present invention is present in an amount more than 7%, preferably in the range of 8-15%, more preferably in the range of 9-13% with respect to unit dose amount. The inventors have found that the dissolution time reduces by 60% in the case that microcrystalline cellulose is used in said amount.
Another aspect of the present invention is the pharmaceutical compositions comprising cefpodoxime proxetil and clavulanic acid or its derivatives wherein microcrystalline cellulose is preferably used in an amount in the range of 8-15%, more preferably in an amount in the range of 9-13% by weight with respect to the weight of the unit dose.
According to these, it has been found that the use of each cellulose-based disintegrant in an amount more than 7% with respect to the unit dose has an important effect on both the increase of dissolution of cefpodoxime proxetil and decrease in dissolution time of the composition comprising cefpodoxime proxetil and clavulanic acid.
The inventors have observed that an optimum particle size of the cellulose-based disintegrant used in the composition of the present invention has a considerable effect on the disintegration and dissolution of the composition. They have found that when the particle size of microcrystalline cellulose used in the present invention is less than 100 μπι, preferably in the range of 30-90 μπι and more preferably in the range of 40-60 μιτι, the dissolution of the composition increases and also dissolution time decreases.
According to this, another aspect of the present invention is pharmaceutical compositions comprising cefpodoxime proxetil and clavulanic acid or its derivatives wherein
microcrystalline cellulose with a particle size less than 100 μηι, preferably in the range of 30- 90 μηι and more preferably in the range of 40-60 μιη is used in the disintegrant combination.
In addition to cefpodoxime proxetil, clavulanic acid, microcrystalline cellulose, croscarmellose, the formulation of the present invention can comprise various excipients such as, but not limited to, glidants, lubricants, diluents, surfactants and optionally coating agents.
The glidant that can be used in the pharmaceutical composition of the present invention can be selected from, but not limited to, a group comprising magnesium silicate, silicon dioxide, starch, talc, tribasic calcium phosphate or combinations thereof.
The lubricant that can be used in the pharmaceutical composition of the present invention can be selected from, but not limited to, a group comprising calcium stearate, magnesium stearate, polyoxyethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, talc, sodium benzoate or combinations thereof. Preferably, magnesium stearate is used as the lubricant in the pharmaceutical composition of the present invention.
The diluent that can be used in the pharmaceutical composition of the present invention can be selected from, but not limited to, a group comprising calcium carbonate, calcium sulfate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, microcrystalline cellulose, lactose, magnesium carbonate, magnesium oxide, maltodextrin, maltose, mannitol, sodium chloride, sorbitol, starch, xylitol or combinations thereof.
The surfactant that can be used in the pharmaceutical composition of the present invention can be selected from, but not limited to, a group comprising docusate sodium, sorbitan esters, cetrimide and sodium lauryl sulfate. In the present invention, sodium lauryl sulfate is preferably used as the surfactant.
The pharmaceutical composition of the present invention can comprise 20-800 mg cefpodoxime proxetil or its pharmaceutically acceptable salts, hydrates, solvates or combinations thereof in an equal amount.
The pharmaceutical composition of the present invention can comprise 50-500 mg clavulanic acid or its pharmaceutically acceptable salts, hydrates, solvates or combinations thereof in an equal amount.
Clavulanic acid and its derivatives (e.g. potassium clavulanate) are extremely susceptible to moisture. To this respect, potassium clavulanate in the pharmaceutical composition is preferably used with a humectant in the ratio of 1 : 1.
One or more of the substances comprising silica; colloidal silica, for instance colloidal silica anhydrous, for example Aerosil® 200, magnesium trisilicate, cellulose powder, Cabosil®, magnesium oxide, calcium silicate, Syloid®, starch, microcrystalline cellulose, talc can be used as the humectant.
In the pharmaceutical composition of the present invention, potassium clavulanate is used with microcrystalline cellulose preferably in the ratio of 1 : 1.
The pharmaceutical composition of the present invention can comprise 5-60% cefpodoxime proxetil in proportion to total weight of unit dose or pharmaceutically acceptable solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms thereof.
The pharmaceutical composition of the present invention can comprise 5-50% clavulanic acid in proportion to total weight of unit dose or pharmaceutically acceptable salts, hydrates, solvates or combinations thereof in an equal amount.
The pharmaceutical composition of the present invention can comprise 5-60% cefpodoxime proxetil; 5-50% potassium clavulanate; 0,5-5% glidant; 0,1-5% lubricant; 0,1-25% disintegrant and/or disintegrants; 1-30% diluent; 0,1-5% surfactant and optionally coating agent of 1-5% of the core weight.
In another aspect, the pharmaceutical composition comprising cefpodoxime proxetil and clavulanic acid prepared according to the present invention can be in conventional tablet, film coated tablet, sachet or capsule form.
In another aspect, the present invention relates to processes for preparation of pharmaceutical compositions comprising pharmaceutically acceptable excipients in addition to cefpodoxime proxetil and clavulanic acid or its derivatives as the active agents.
According to this, the process of the present invention comprises the steps of granulating the active agent cefpodoxime proxetil and clavulanic acid or its derivatives by conventional wet and/or dry granulation methods; or powdering cefpodoxime proxetil, clavulanic acid derivatives and other excipients after mixing them by dry blending method and
- compressing the pharmaceutical composition of the present invention in tablet form and optionally coating the tablets with a coating agent in the case that the product is developed in tablet form and/or,
filling the pharmaceutical composition of the present invention in capsules in the case that the product is developed in tablet form and/or,
filling the pharmaceutical composition of the present invention in packs in the case that the product is developed in sachet form.
Another aspect of the present invention is that the formulation prepared according to said invention is used in the treatment of diseases related with infections caused by gram negative and gram positive bacteria.
According to another aspect of the present invention, the pharmaceutical composition prepared according to the present invention is used in the production of a medicament so as to be used in upper respiratory infections such as ear, nose, throat, otitis media, sinusitis, tonsillitis, pharyngitis; lower respiratory tract infections such as pyelonephritis, cystitis and urethritis; skin or soft tissue infections such as froncle, pyoderma, impetigo; in the treatment and prophylaxis of gonorrhea and lyme diseases.
The pharmaceutical composition of the present invention can be prepared as described below, but not limited to the examples given.
EXAMPLE 1: Formulation and process for preparation of film tablet comprising cefpodoxime proxetil and potasium clavulanate
According to this, a process for preparation of pharmaceutical compositions is composed of the steps of mixing and compressing cefpodoxime proxetil, the disintegrant and the diluent and then sieving them; adding the surfactant, potassium clavulanate: avicel, disintegrant, glidant and lubricant into the granules obtained and mixing them; and then compressing tablets of the mixture obtained and coating the tablets with coating material.
Claims
1. A pharmaceutical composition composed of a combination of cefpodoxime proxetil and clavulanic acid or its derivatives, wherein;
said composition comprises a combination of croscarmellose sodium and microcrystalline cellulose mixture as the disintegrant
- each one of the cellulose-based disintegrants is present in an amount more than 7% by weight with respect to the weight of the unit dose.
2. The pharmaceutical composition according to claim 1, wherein cefpodoxime proxetil comprised in said composition is in the form of its solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms or in free form and/or combinations thereof.
3. The pharmaceutical composition according to claim 1, wherein clavulanic acid comprised in said composition is in the form of its solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms or in free form and/or combinations thereof.
4. The pharmaceutical composition according to claim 3, wherein potassium clavulanate is used in said composition.
5. The pharmaceutical composition according to claim 1, wherein said composition comprises 8-15% croscarmellose sodium.
6. The pharmaceutical composition according to claim 5, wherein said composition comprises 9-12% croscarmellose sodium.
7. The pharmaceutical composition according to claim 1, wherein the particle size of microcrystalline cellulose used is less than 100 μπι.
8. The pharmaceutical composition according to claim 7, wherein the particle size of microcrystalline cellulose used is in the range of 30-90 μιη.
9. The pharmaceutical composition according to claim 8, wherein the particle size of microcrystalline cellulose used is in the range of 40-60 μιη.
10. The pharmaceutical composition according to claim 1, wherein said composition comprises 8-15% microcrystalline cellulose.
11. The pharmaceutical composition according to claim 10, wherein said composition comprises 9-13% microcrystalline cellulose.
12. The pharmaceutical composition according to claim 1, wherein said composition comprises one or more excipients such as glidant, lubricant, surfactant and optionally coating agents in addition to cefpodoxime proxetil, potassium clavulanate, microcrystalline cellulose and croscarmellose sodium.
13. The pharmaceutical composition according to claim 12, wherein the diluent is selected from a group comprising calcium carbonate, calcium sulfate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, microcrystalline cellulose, lactose, magnesium carbonate, magnesium oxide, maltodextrin, maltose, mannitol, sodium chloride, sorbitol, starch, xylitol or combinations thereof.
14. The pharmaceutical composition according to claim 12, wherein the glidant is selected from a group comprising magnesium silicate, silicon dioxide, starch, talc, tribasic calcium phosphate or combinations thereof.
15. The pharmaceutical composition according to claim 12, wherein the lubricant is selected from a group comprising calcium stearate, magnesium stearate, polyoxyethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, talc, sodium benzoate or combinations thereof.
16. The pharmaceutical composition according to claim 15, wherein magnesium stearate is used as the lubricant in said formulation.
17. The pharmaceutical composition according to claim 12, wherein the surfactant is selected from a group comprising docusate sodium, sorbitan esters, cetrimide and sodium lauryl sulfate.
18. The pharmaceutical composition according to claim 1, wherein said composition comprises 20-800 mg cefpodoxime proxetil or its pharmaceutically acceptable salts, hydrates, solvates or combinations thereof in an equal amount.
19. The pharmaceutical composition according to claim 1, wherein said composition comprises 50-500 mg clavulanic acid or its pharmaceutically acceptable salts, hydrates, solvates or combinations thereof in an equal amount.
20. The pharmaceutical composition according to claim 1 , wherein clavulanic acid or its derivative is used with a humectant in the ratio of 1 : 1.
21. The pharmaceutical composition according to claim 20, wherein the humectant to be used together with clavulanic acid is selected from a group comprising silica, colloidal silicon dioxide, magnesium trisilicate, cellulose powder, magnesium oxide, calcium silicate, starch, talc or microcrystalline cellulose.
22. The pharmaceutical composition according to claim 21, wherein the humectant to be used together with clavulanic acid is microcrystalline cellulose.
23. The pharmaceutical composition according to claim 1, wherein said composition comprises 5-60% cefpodoxime proxetil or pharmaceutically acceptable solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms thereof in an equal amount.
24. The pharmaceutical composition according to claim 1, wherein said composition comprises 5-50% clavulanic acid or pharmaceutically acceptable solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms thereof in an equal amount.
25. The pharmaceutical composition according to claim 1, wherein said composition comprises 5-60% cefpodoxime proxetil; 5-50% potassium clavulanate; 0,5-5% glidant; 0,1-5% lubricant; 0,1-25% disintegrant and/or disintegrants; 1-30% diluent; 0,1-5% surfactant in proportion to total weight of unit dose amount and optionally coating agent of 1-5%) of the core weight.
26. The pharmaceutical composition according to claim 1, wherein said composition is used in conventional tablet, film coated tablet, sachet or capsule.
27. A process for preparation of the pharmaceutical composition claimed in claim 1, wherein said process composes the steps of granulating the active agents cefpodoxime proxetil and clavulanic acid or its derivatives by conventional wet and/or dry granulation methods; or powdering cefpodoxime proxetil, clavulanic acid and other excipients after mixing them by dry blending method.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11770579.8A EP2575777A1 (en) | 2010-06-03 | 2011-06-02 | Formulation comprising cefpodoxime proxetil and clavulanic acid |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR201004467 | 2010-06-03 | ||
| TR2010/04467 | 2010-06-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2011152808A1 true WO2011152808A1 (en) | 2011-12-08 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/TR2011/000148 WO2011152808A1 (en) | 2010-06-03 | 2011-06-02 | Formulation comprising cefpodoxime proxetil and clavulanic acid |
Country Status (2)
| Country | Link |
|---|---|
| EP (1) | EP2575777A1 (en) |
| WO (1) | WO2011152808A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013151517A1 (en) * | 2012-04-04 | 2013-10-10 | Mahmut Bilgic | Tablet formulations comprising cefpodoxime proxetil and clavulanic acid |
| WO2014123500A1 (en) * | 2013-02-11 | 2014-08-14 | Bilgiç Mahmut | Pharmaceutical formulations comprising cefpodoxime proxetil and clavulanic acid |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0049118A2 (en) | 1980-09-30 | 1982-04-07 | Sankyo Company Limited | Cephalosporin derivatives, their preparation and compositions containing them |
| EP0593573A1 (en) | 1991-07-11 | 1994-04-27 | Smithkline Beecham Plc | Pharmaceutical formulation of a beta-lactam antibiotic and clavulanic acid or a water-soluble salt thereof |
| WO1998001114A1 (en) * | 1996-07-03 | 1998-01-15 | Yamanouchi Europe B.V. | Granulate for the preparation of fast-disintegrating and fast-dissolving compositions containing a high amount of drug |
| WO2004006917A1 (en) * | 2002-07-16 | 2004-01-22 | Ranbaxy Laboratories Limited | Dispersible tablets for oral administration |
| WO2005065685A1 (en) * | 2004-01-06 | 2005-07-21 | Panacea Biotec Ltd. | Controlled release pharmaceutical composition comprising an acid-insoluble polymer and a bioadhesive polymer |
| WO2007110875A1 (en) * | 2006-03-24 | 2007-10-04 | Panacea Biotec Ltd. | Antibiotic compositions of modified release and process of production thereof |
-
2011
- 2011-06-02 WO PCT/TR2011/000148 patent/WO2011152808A1/en active Application Filing
- 2011-06-02 EP EP11770579.8A patent/EP2575777A1/en not_active Withdrawn
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0049118A2 (en) | 1980-09-30 | 1982-04-07 | Sankyo Company Limited | Cephalosporin derivatives, their preparation and compositions containing them |
| EP0593573A1 (en) | 1991-07-11 | 1994-04-27 | Smithkline Beecham Plc | Pharmaceutical formulation of a beta-lactam antibiotic and clavulanic acid or a water-soluble salt thereof |
| WO1998001114A1 (en) * | 1996-07-03 | 1998-01-15 | Yamanouchi Europe B.V. | Granulate for the preparation of fast-disintegrating and fast-dissolving compositions containing a high amount of drug |
| WO2004006917A1 (en) * | 2002-07-16 | 2004-01-22 | Ranbaxy Laboratories Limited | Dispersible tablets for oral administration |
| WO2005065685A1 (en) * | 2004-01-06 | 2005-07-21 | Panacea Biotec Ltd. | Controlled release pharmaceutical composition comprising an acid-insoluble polymer and a bioadhesive polymer |
| WO2007110875A1 (en) * | 2006-03-24 | 2007-10-04 | Panacea Biotec Ltd. | Antibiotic compositions of modified release and process of production thereof |
Non-Patent Citations (1)
| 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 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013151517A1 (en) * | 2012-04-04 | 2013-10-10 | Mahmut Bilgic | Tablet formulations comprising cefpodoxime proxetil and clavulanic acid |
| WO2014123500A1 (en) * | 2013-02-11 | 2014-08-14 | Bilgiç Mahmut | Pharmaceutical formulations comprising cefpodoxime proxetil and clavulanic acid |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2575777A1 (en) | 2013-04-10 |
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