WO2012060786A2 - Cefpodoxime proxetil formulations comprising viscosity agent - Google Patents
Cefpodoxime proxetil formulations comprising viscosity agent Download PDFInfo
- Publication number
- WO2012060786A2 WO2012060786A2 PCT/TR2011/000251 TR2011000251W WO2012060786A2 WO 2012060786 A2 WO2012060786 A2 WO 2012060786A2 TR 2011000251 W TR2011000251 W TR 2011000251W WO 2012060786 A2 WO2012060786 A2 WO 2012060786A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- agent
- pharmaceutical composition
- composition according
- range
- carboxymethyl cellulose
- Prior art date
Links
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
- A61K9/14—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
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Definitions
- the present invention relates to pharmaceutical formulations comprising cefpodoxime and optionally clavulanic acid or derivatives thereof.
- Cefpodoxime proxetil is a third generation cephalosporin. Due to this feature, it is indicated for the treatment of infections caused by gram positive and gram negative bacteria.
- Clavulanic acid and derivatives thereof are known as the beta-lactamase inhibitors which withstand the beta-lactamase-originated resistance mechanism by suppressing the activity of beta-lactamase enzymes produced by bacteria.
- Clavulanic acid and derivatives thereof can optionally be formulated as combined with antibiotics in order to increase efficiency of beta-lactam derivative antibiotics.
- Tablets which contain 100 mg and 200 mg of cefpodoxime are available on the market. When these tablets containing 100 or 200 mg of active agent are formulated with excipients, they become quite large in size and this makes use of this dosage form inconvenient for patients who have swallowing difficulties, especially for pediatric and geriatric patients.
- cefpodoxime has quite low water solubility; therefore bioavailability of tablet forms thereof is rather low. It is known that efficiency of a drug depends on the design of the pharmaceutical formulation to a great extent. When highly hydrophobic nature of cephalosporins, especially cefpodoxime, are taken into consideration, it is seen that selecting each agent to be used in the formulation carefully is significant to attain to the desired level of bioavailability in the dosage forms constituted.
- cefpodoxime has rather low water solubility makes development of water dispersible cefpodoxime formulations difficult. These cefpodoxime formulations do not disperse in water homogeneously due to low water solubility of cefpodoxime.
- cefpodoxime is a hydrophobic molecule. Therefore, it has low water solubility leading to gelling problem of the water dispersible formulations comprising cefpodoxime. Gelling is also an important problem which makes the development of water dispersible cefpodoxime formulations difficult. Accordingly, there is need for formulations comprising cefpodoxime and optionally clavulanic acid or derivatives thereof which have higher bioavailability than solid oral dosage forms; can dissolve in water homogeneously; have no gelling problem in order to meet the needs of the patients in special conditions, for example pediatric and geriatric patients.
- the subject matter of the present invention is formulations comprising water dispersible cefpodoxime which comprise a viscosity agent comprising hydroxypropyl cellulose and at least one carboxymethyl cellulose derivative agent and optionally clavulanic acid or derivatives thereof.
- powder, tablet and/or granules comprising the active agent cefpodoxime and a viscosity agent composition, wherein the ratio of carboxymethyl cellulose derivative agent to hydroxypropyl cellulose is in the range of 15: 1 and 5:1, preferably 12:1 and 6:1, more preferably 10:1 and 7:1 by weight and carboxymethyl cellulose derivative agent is selected from carboxymethyl cellulose calcium, carboxymethyl cellulose sodium or a combination thereof, constitute a suspension which is dispersed in water without gelling.
- compositions in the form of water dispersible powder, tablet and/or granule can be taken by patients more comfortably than the solid dosage forms as they disperse in water homogeneously and their bioavailability is superior to said solid dosage forms; b) the problem of gelling which is frequently encountered in cefpodoxime formulations is overcome in this way.
- Cefpodoxime that can be used in water dispersible powder, tablet and/or granule formulations of the present invention can be in the form of its esters, solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms or free form and or a combination thereof.
- cefpodoxime proxetil is used in the present invention.
- water dispersible powder , tablet and/or granule stated in the text comprises single dose effervescent powder, tablets and/or granules; single dose water dispersible powder, tablets and granules; multiple dose powder, tablets and granules which are dispersed in water to form suspension; single dose water soluble powder, tablets and granules; multiple dose water soluble powder, tablets and granules, preferably in the form of multiple dose powder dispersed in water to form suspension or single dose water dispersible powder, tablets or granules.
- one aspect of the present invention is water dispersible powder, tablet and/or granule formulations comprising cefpodoxime characterized in that;
- composition comprises hydroxypropyl cellulose and at least one carboxymethyl cellulose derivative agent combination
- the ratio of carboxymethyl cellulose derivative agent to hydroxypropyl cellulose is in the range of 15:1 and 5:1, preferably 12:1 and 6:1, more preferably 10:1 and 7:1 by weight and
- carboxymethyl cellulose derivative agent is selected from carboxymethyl cellulose calcium, carboxymethyl cellulose sodium or a combination thereof.
- the viscosity agent that can be used in water dispersible powder, tablet and/or granule formulation of the present invention is composed of hydroxypropyl cellulose and at least one carboxymethylcellulose derivative agent.
- carboxymethylcellulose derivative agent refers to alkali and alkaline-earth salts of carboxymethyl cellulose.
- the inventors have found that water dispersity of a pharmaceutical composition obtained by use of combination of carboxymethyl cellulose sodium and carboxymethyl cellulose calcium is better than the other pharmaceutical compositions in which only one of said agents is used.
- present invention relates to water dispersible cefpodoxime formulations comprising a viscosity agent combination comprising hydroxypropyl cellulose, carboxymethyl cellulose sodium and carboxymethyl cellulose calcium.
- the ratio of carboxymethyl cellulose calcium to carboxymethyl cellulose sodium in said viscosity agent combination is in the range of 5:1 and 1 :1 by weight, preferably in the range of 4:1 and 2:1 by weight.
- tablet hardness should be taken into consideration since this parameter affects the dissolution time of the tablets, thus the bioavailability of cefpodoxime proxetil.
- the formulations comprising hydroxypropyl cellulose having an average particle size in the range of 5-100 ⁇ , preferably 10-90 ⁇ and the carboxymethyl cellulose derivative having an average particle size in the range of 10-150 ⁇ , preferably 20-100 ⁇ have an optimum hardness and thus rapid dissolution leading to an increase in the bioavailability of cefpodoxime proxetil.
- water dispersible tablet formulations comprising cefpodoxime proxetil wherein hydroxypropyl cellulose has an average particle size in the range of 5-100 ⁇ , preferably 10-90 ⁇ and the carboxymethyl cellulose derivative having an average particle size in the range of 10-150 ⁇ , preferably 20-100 ⁇ .
- Another aspect of the present invention is water dispersible powder, tablet and/or granule formulations comprising cefpodoxime as the active agent; viscosity agent composition comprising hydroxypropyl cellulose and at least one carboxymethyl cellulose derivative agent combination; and additionally other pharmaceutically acceptable excipients.
- the water dispersible powder, tablet and/or granule formulation can comprise various excipients such as, but not limited to, binders, lubricants, humectants, antiadherents, disintegrants, diluents, basic agents, acidic agents, taste regulating agents, flavoring agents, preservative agents and optionally effervescent couple.
- excipients such as, but not limited to, binders, lubricants, humectants, antiadherents, disintegrants, diluents, basic agents, acidic agents, taste regulating agents, flavoring agents, preservative agents and optionally effervescent couple.
- the binder that can be used in water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising ethyl cellulose, gelatine, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminum silicate, methyl cellulose, povidone or the combination thereof.
- the lubricant that can be used in water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising calcium stearate, magnesium stearate, polyethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, talc, sodium benzoate or the combination thereof.
- talc is used as lubricant in the formulation of the present invention.
- the humectant that can be used in the water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising anhydrous sodium sulphate, silica gel and potassium carbonate or the combination thereof.
- the antiadherent that can be used in the water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising talc, corn starch, colloidal silica, L-leucine, sodium sulfate, magnesium stearate and sodium stearate.
- the disintegrant that can be used in water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising carboxymethyl cellulose calcium, carboxymethyl cellulose sodium, microcrystalline cellulose, silicon dioxide, croscarmellose sodium, crospovidone, hydroxypropyl cellulose, methyl cellulose, povidone, magnesium aluminum silicate and starch or combinations thereof.
- the diluent that can be used in water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising calcium carbonate, calcium sulphate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulphate, microcrystalline cellulose, lactose, magnesium carbonate, magnesium oxide, maltodextrin, maltose, mannitol, sodium chloride, sorbitol, starch, xylitol or combinations thereof.
- the basic agent that can be used in the water dispersible powder, tablet and/or granule formulation of the present invention can be selected from a group comprising potassium carbonate, potassium bicarbonate, potassium citrate, potassium hydroxide, sodium carbonate, sodium bicarbonate or combinations thereof.
- the acidic agent that can be used in the water dispersible powder, tablet and/or granule formulation of the present invention can be selected from a group comprising acetic acid, citric acid, lactic acid, malic acid, phosphoric acid, propionic acid, tartaric acid or combinations thereof.
- citric acid is used in the formulation of the present invention as acidic agent.
- the taste regulating agent that can be used in water dispersible powder, tablet and/or granule formulation of the present invention can be selected from a group comprising acesulfame, aspartame, dextrose, fructose, glucose, lactitol, maltitol, maltose, sorbitol, saccharine, saccharine sodium, sodium cyclamate, sucralose, sodium chloride, potassium chloride, sucrose, xylitol or combinations thereof.
- the preservative agent that can be used in water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising methylparaben, ethylparaben, butylparaben, sorbic acid, tertiary ammonium salts, potassium sorbate, benzoic acid and/or salts thereof (sodium benzoate) and benzyl alcohol or combinations thereof.
- the effervescent couple that can optionally be used in water dispersible powder, tablet and granule formulation of the present invention can be selected from organic acids such as citric acid, tartaric acid, malic acid, fumaric acid and basic agents such as sodium hydrogen carbonate, sodium carbonate, potassium carbonate and potassium hydrogen carbonate
- the water dispersible powder, tablet and granule formulation of the present invention can comprise cefpodoxime in the range of 20-800 mg or its pharmaceutically acceptable esters, salts, hydrates, solvates or a combination thereof in an equal amount.
- the water dispersible powder, tablet and granule formulation of the present invention can comprise 5-40% of cefpodoxime or its pharmaceutically acceptable esters, solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms in proportion to total weight of unit dose.
- the water dispersible powder, tablet and granule formulation of the present invention can comprise 5-40 % of cefpodoxime and at least one; binder in the range of 0-30%; lubricant in the range of 2-10%; humectant in the range of 0-30%; antiadherent in the range of %1-10; disintegrant and/or disintegrants in the range of 0-15%; diluent in the range of 35-60%; basic agent in the range of 0-30%; acidic agent in the range of 0.1 - 15 %; taste regulating agent in the range of 10-30%; viscosity agent in the range of 4-15%; flavoring agent in the range of 0.5- 3%; preservative agent in the range of 0-3% and optionally effervescent couple in the range of 0-80% in proportion to the total weight of unit dose amount.
- the formulation of the present invention is related to the pharmaceutical compositions comprising cefpodoxime and optionally clavulanic acid or derivatives thereof.
- the present invention relates to pharmaceutical compositions comprising cefpodoxime and clavulanic acid or derivatives thereof, viscosity agent composition comprising hydroxypropyl cellulose and at least one carboxymethyl cellulose derivative agent combination; and optionally pharmaceutically acceptable excipients in addition.
- Clavulanic acid that can optionally 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 form and/or a combination thereof.
- potassium clavulanate is used in the present invention.
- the pharmaceutical composition of the present invention can comprise clavulanic acid in the range of 50-500 mg or its pharmaceutically acceptable salts, hydrates, solvates or the combination thereof in an equal amount.
- Clavulanic acid and its derivatives are extremely susceptible to moisture.
- potassium clavulanate is preferably used with a humectant in the ratio of 1 :1 in the pharmaceutical composition of the present invention.
- colloidal silica for instance colloidal silica anhydrous, magnesium trisilicate, cellulose powder, magnesium oxide, calcium silicate, starch, microcrystalline cellulose, talc can be used as the humectant.
- potassium clavulanate is preferably used with syloid in the ratio of 1 : 1.
- the pharmaceutical composition of the present invention can comprise 5-50% of clavulanic acid in proportion to total weight of unit dose amount or pharmaceutically acceptable salts, hydrates, solvates or combinations thereof in an equal amount.
- the present invention relates to processes that can be used for preparation of water dispersible powder, tablet and/or granule formulations comprising pharmaceutically acceptable excipients in addition to cefpodoxime as the active agent and a viscosity agent composition.
- the process of the present invention comprises granulation of the active agent cefpodoxime proxetil by conventional wet and/or dry granulation methods; or powdering cefpodoxime proxetil and other excipients after mixing them by dry blending method and optionally compressing tablets.
- the powder, tablet and/or granules obtained are dispersed in water before use by patients and taken in liquid form.
- Another aspect of the present invention is that the formulation prepared according to said invention is used in the treatment of diseases related with infections caused by gram negative and gram positive bacteria.
- Water dispersible tablets of the present invention can be prepared as specified below, yet the invention is not restricted to these examples.
- EXAMPLE 1 Formulation and process for preparation of water dispersible granule
- a method for preparation of water dispersible granule given in the example comprises, but not limited to, dissolving cefpodoxime proxetil in a suitable solvent; and granulating the diluent with this solution; and drying and then mixing the obtained granules with the other excipients which are lubricant, viscosity agent comprising hydroxypropyl cellulose and carboxymethyl cellulose derivative, taste regulating agent, acidic agent, antiadherent and flavouring agent.
- a method for preparation of water dispersible granule given in this example comprises, but not limited to, dissolving cefpodoxime proxetil in a suitable solvent; and granulating the diluent with this solution; and drying and then mixing the granules obtained with potassium clavylanate-syloid (1 :1) and the other excipients which are lubricant, viscosity agent comprising hydroxypropyl cellulose and carboxymethyl cellulose derivative, taste regulating agent, acidic agent, antiadherent and flavouring agent.
- EXAMPLE 3 Formulation and process for preparation of water dispersible tablet
- a method for preparation of water dispersible granules given in the example comprises, but not limited to, dissolving cefpodoxime proxetil in a suitable solvent; and granulating the diluent with this solution; and drying and then mixing the obtained granules with the other excipients which are lubricant, viscosity agent comprising hydroxypropyl cellulose, calcium carboxymethyl cellulose and sodium carboxymethyl cellulose, taste regulating agent, acidic agent, antiadherent and flavouring agent.
Abstract
The present invention relates to pharmaceutical formulations comprising cefpodoxime proxetil.
Description
CEFPODOXIME PROXETIL FORMULATIONS COMPRISING VISCOSITY
AGENT
The present invention relates to pharmaceutical formulations comprising cefpodoxime and optionally clavulanic acid or derivatives thereof. Background of the Invention:
Cefpodoxime proxetil (Figure I), chemical name of which pivaloyloxymethyl 7-[2-(2-amino- thiazole-4-yl]-2-(syn)-methoxyimino-acetamido]-3-methoxymethyl-3-cefem-4-carboxyIate, was first disclosed in the patent number EP0049118.
Cefpodoxime proxetil is a third generation cephalosporin. Due to this feature, it is indicated for the treatment of infections caused by gram positive and gram negative bacteria.
Clavulanic acid and derivatives thereof (for instance its salts such as potassium clavulanate) are known as the beta-lactamase inhibitors which withstand the beta-lactamase-originated resistance mechanism by suppressing the activity of beta-lactamase enzymes produced by bacteria. Clavulanic acid and derivatives thereof can optionally be formulated as combined with antibiotics in order to increase efficiency of beta-lactam derivative antibiotics.
Tablets which contain 100 mg and 200 mg of cefpodoxime are available on the market. When these tablets containing 100 or 200 mg of active agent are formulated with excipients, they become quite large in size and this makes use of this dosage form inconvenient for patients who have swallowing difficulties, especially for pediatric and geriatric patients.
The molecule cefpodoxime has quite low water solubility; therefore bioavailability of tablet forms thereof is rather low.
It is known that efficiency of a drug depends on the design of the pharmaceutical formulation to a great extent. When highly hydrophobic nature of cephalosporins, especially cefpodoxime, are taken into consideration, it is seen that selecting each agent to be used in the formulation carefully is significant to attain to the desired level of bioavailability in the dosage forms constituted.
In order to overcome the difficulties resulting from the use of the solid dosage form, water dispersible dosage forms have been developed. However, the fact that cefpodoxime has rather low water solubility makes development of water dispersible cefpodoxime formulations difficult. These cefpodoxime formulations do not disperse in water homogeneously due to low water solubility of cefpodoxime.
Moreover, cefpodoxime is a hydrophobic molecule. Therefore, it has low water solubility leading to gelling problem of the water dispersible formulations comprising cefpodoxime. Gelling is also an important problem which makes the development of water dispersible cefpodoxime formulations difficult. Accordingly, there is need for formulations comprising cefpodoxime and optionally clavulanic acid or derivatives thereof which have higher bioavailability than solid oral dosage forms; can dissolve in water homogeneously; have no gelling problem in order to meet the needs of the patients in special conditions, for example pediatric and geriatric patients.
Description of the Invention: The subject matter of the present invention is formulations comprising water dispersible cefpodoxime which comprise a viscosity agent comprising hydroxypropyl cellulose and at least one carboxymethyl cellulose derivative agent and optionally clavulanic acid or derivatives thereof. It has surprisingly been seen that powder, tablet and/or granules comprising the active agent cefpodoxime and a viscosity agent composition, wherein the ratio of carboxymethyl cellulose derivative agent to hydroxypropyl cellulose is in the range of 15: 1 and 5:1, preferably 12:1 and 6:1, more preferably 10:1 and 7:1 by weight and carboxymethyl cellulose derivative agent is selected from carboxymethyl cellulose calcium, carboxymethyl cellulose sodium or a combination thereof, constitute a suspension which is dispersed in water without gelling. Accordingly, pharmaceutical dosage forms in the form of water dispersible powder, tablet and/or granule;
a) can be taken by patients more comfortably than the solid dosage forms as they disperse in water homogeneously and their bioavailability is superior to said solid dosage forms; b) the problem of gelling which is frequently encountered in cefpodoxime formulations is overcome in this way. Cefpodoxime that can be used in water dispersible powder, tablet and/or granule formulations of the present invention can be in the form of its esters, solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms or free form and or a combination thereof. Preferably, cefpodoxime proxetil is used in the present invention. The term "water dispersible powder , tablet and/or granule" stated in the text comprises single dose effervescent powder, tablets and/or granules; single dose water dispersible powder, tablets and granules; multiple dose powder, tablets and granules which are dispersed in water to form suspension; single dose water soluble powder, tablets and granules; multiple dose water soluble powder, tablets and granules, preferably in the form of multiple dose powder dispersed in water to form suspension or single dose water dispersible powder, tablets or granules.
According to this, one aspect of the present invention is water dispersible powder, tablet and/or granule formulations comprising cefpodoxime characterized in that;
- said composition comprises hydroxypropyl cellulose and at least one carboxymethyl cellulose derivative agent combination,
- the ratio of carboxymethyl cellulose derivative agent to hydroxypropyl cellulose is in the range of 15:1 and 5:1, preferably 12:1 and 6:1, more preferably 10:1 and 7:1 by weight and
- carboxymethyl cellulose derivative agent is selected from carboxymethyl cellulose calcium, carboxymethyl cellulose sodium or a combination thereof.
Another aspect of the present invention is that the viscosity agent that can be used in water dispersible powder, tablet and/or granule formulation of the present invention is composed of hydroxypropyl cellulose and at least one carboxymethylcellulose derivative agent.
The term "carboxymethylcellulose derivative agent" stated in the text refers to alkali and alkaline-earth salts of carboxymethyl cellulose.
The inventors have found that water dispersity of a pharmaceutical composition obtained by use of combination of carboxymethyl cellulose sodium and carboxymethyl cellulose calcium is better than the other pharmaceutical compositions in which only one of said agents is used.
According to this, present invention relates to water dispersible cefpodoxime formulations comprising a viscosity agent combination comprising hydroxypropyl cellulose, carboxymethyl cellulose sodium and carboxymethyl cellulose calcium.
The ratio of carboxymethyl cellulose calcium to carboxymethyl cellulose sodium in said viscosity agent combination is in the range of 5:1 and 1 :1 by weight, preferably in the range of 4:1 and 2:1 by weight. In the case that the water dispersible formulation is formulated in tablet form, tablet hardness should be taken into consideration since this parameter affects the dissolution time of the tablets, thus the bioavailability of cefpodoxime proxetil. It has been observed that the formulations comprising hydroxypropyl cellulose having an average particle size in the range of 5-100 μπι, preferably 10-90 μηι and the carboxymethyl cellulose derivative having an average particle size in the range of 10-150 μιη, preferably 20-100 μηι have an optimum hardness and thus rapid dissolution leading to an increase in the bioavailability of cefpodoxime proxetil.
Accordingly, another aspect of the present invention is water dispersible tablet formulations comprising cefpodoxime proxetil wherein hydroxypropyl cellulose has an average particle size in the range of 5-100 μηι, preferably 10-90 μιη and the carboxymethyl cellulose derivative having an average particle size in the range of 10-150 μιη, preferably 20-100 μπι.
Another aspect of the present invention is water dispersible powder, tablet and/or granule formulations comprising cefpodoxime as the active agent; viscosity agent composition comprising hydroxypropyl cellulose and at least one carboxymethyl cellulose derivative agent combination; and additionally other pharmaceutically acceptable excipients.
Apart from cefpodoxime and viscosity agent composition comprising hydroxypropyl cellulose and at least one carboxymethyl cellulose derivative agent combination; the water dispersible powder, tablet and/or granule formulation can comprise various excipients such as, but not limited to, binders, lubricants, humectants, antiadherents, disintegrants, diluents, basic agents, acidic agents, taste regulating agents, flavoring agents, preservative agents and optionally effervescent couple.
The binder that can be used in water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising ethyl cellulose, gelatine, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminum silicate, methyl cellulose, povidone or the combination thereof. The lubricant that can be used in water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising calcium stearate, magnesium stearate, polyethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, talc, sodium benzoate or the combination thereof. Preferably, talc is used as lubricant in the formulation of the present invention. The humectant that can be used in the water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising anhydrous sodium sulphate, silica gel and potassium carbonate or the combination thereof.
The antiadherent that can be used in the water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising talc, corn starch, colloidal silica, L-leucine, sodium sulfate, magnesium stearate and sodium stearate.
The disintegrant that can be used in water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising carboxymethyl cellulose calcium, carboxymethyl cellulose sodium, microcrystalline cellulose, silicon dioxide, croscarmellose sodium, crospovidone, hydroxypropyl cellulose, methyl cellulose, povidone, magnesium aluminum silicate and starch or combinations thereof.
The diluent that can be used in water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising calcium carbonate, calcium sulphate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulphate, microcrystalline cellulose, lactose, magnesium carbonate, magnesium oxide, maltodextrin, maltose, mannitol, sodium chloride, sorbitol, starch, xylitol or combinations thereof.
The basic agent that can be used in the water dispersible powder, tablet and/or granule formulation of the present invention can be selected from a group comprising potassium carbonate, potassium bicarbonate, potassium citrate, potassium hydroxide, sodium carbonate, sodium bicarbonate or combinations thereof.
The acidic agent that can be used in the water dispersible powder, tablet and/or granule formulation of the present invention can be selected from a group comprising acetic acid, citric acid, lactic acid, malic acid, phosphoric acid, propionic acid, tartaric acid or combinations thereof. Preferably, citric acid is used in the formulation of the present invention as acidic agent.
The taste regulating agent that can be used in water dispersible powder, tablet and/or granule formulation of the present invention can be selected from a group comprising acesulfame, aspartame, dextrose, fructose, glucose, lactitol, maltitol, maltose, sorbitol, saccharine, saccharine sodium, sodium cyclamate, sucralose, sodium chloride, potassium chloride, sucrose, xylitol or combinations thereof.
The preservative agent that can be used in water dispersible powder, tablet and granule formulation of the present invention can be selected from a group comprising methylparaben, ethylparaben, butylparaben, sorbic acid, tertiary ammonium salts, potassium sorbate, benzoic acid and/or salts thereof (sodium benzoate) and benzyl alcohol or combinations thereof. The effervescent couple that can optionally be used in water dispersible powder, tablet and granule formulation of the present invention can be selected from organic acids such as citric acid, tartaric acid, malic acid, fumaric acid and basic agents such as sodium hydrogen carbonate, sodium carbonate, potassium carbonate and potassium hydrogen carbonate
The water dispersible powder, tablet and granule formulation of the present invention can comprise cefpodoxime in the range of 20-800 mg or its pharmaceutically acceptable esters, salts, hydrates, solvates or a combination thereof in an equal amount.
The water dispersible powder, tablet and granule formulation of the present invention can comprise 5-40% of cefpodoxime or its pharmaceutically acceptable esters, solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms in proportion to total weight of unit dose.
The water dispersible powder, tablet and granule formulation of the present invention can comprise 5-40 % of cefpodoxime and at least one; binder in the range of 0-30%; lubricant in the range of 2-10%; humectant in the range of 0-30%; antiadherent in the range of %1-10; disintegrant and/or disintegrants in the range of 0-15%; diluent in the range of 35-60%; basic agent in the range of 0-30%; acidic agent in the range of 0.1 - 15 %; taste regulating agent in the range of 10-30%; viscosity agent in the range of 4-15%; flavoring agent in the range of 0.5-
3%; preservative agent in the range of 0-3% and optionally effervescent couple in the range of 0-80% in proportion to the total weight of unit dose amount.
The formulation of the present invention is related to the pharmaceutical compositions comprising cefpodoxime and optionally clavulanic acid or derivatives thereof. According to this, the present invention relates to pharmaceutical compositions comprising cefpodoxime and clavulanic acid or derivatives thereof, viscosity agent composition comprising hydroxypropyl cellulose and at least one carboxymethyl cellulose derivative agent combination; and optionally pharmaceutically acceptable excipients in addition.
Clavulanic acid that can optionally 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 form and/or a combination thereof. Preferably, potassium clavulanate is used in the present invention.
The pharmaceutical composition of the present invention can comprise clavulanic acid in the range of 50-500 mg or its pharmaceutically acceptable salts, hydrates, solvates or the combination thereof in an equal amount.
Clavulanic acid and its derivatives (e.g. potassium clavulanate) are extremely susceptible to moisture. To this respect, potassium clavulanate is preferably used with a humectant in the ratio of 1 :1 in the pharmaceutical composition of the present invention.
One or more of the substances comprising silica; colloidal silica, for instance colloidal silica anhydrous, magnesium trisilicate, cellulose powder, magnesium oxide, calcium silicate, starch, microcrystalline cellulose, talc can be used as the humectant.
In the pharmaceutical composition of the present invention, potassium clavulanate is preferably used with syloid in the ratio of 1 : 1.
The pharmaceutical composition of the present invention can comprise 5-50% of clavulanic acid in proportion to total weight of unit dose amount or pharmaceutically acceptable salts, hydrates, solvates or combinations thereof in an equal amount.
In another aspect, the present invention relates to processes that can be used for preparation of water dispersible powder, tablet and/or granule formulations comprising pharmaceutically
acceptable excipients in addition to cefpodoxime as the active agent and a viscosity agent composition.
According to this, the process of the present invention comprises granulation of the active agent cefpodoxime proxetil by conventional wet and/or dry granulation methods; or powdering cefpodoxime proxetil and other excipients after mixing them by dry blending method and optionally compressing tablets.
The powder, tablet and/or granules obtained are dispersed in water before use by patients and taken in liquid form.
Another aspect of the present invention is that the formulation prepared according to said invention is used in the treatment of diseases related with infections caused by gram negative and gram positive bacteria.
Water dispersible tablets of the present invention can be prepared as specified below, yet the invention is not restricted to these examples.
EXAMPLE 1: : Formulation and process for preparation of water dispersible granule
A method for preparation of water dispersible granule given in the example comprises, but not limited to, dissolving cefpodoxime proxetil in a suitable solvent; and granulating the diluent
with this solution; and drying and then mixing the obtained granules with the other excipients which are lubricant, viscosity agent comprising hydroxypropyl cellulose and carboxymethyl cellulose derivative, taste regulating agent, acidic agent, antiadherent and flavouring agent.
EXAMPLE 2: Formulation and process for preparation of water dispersible granule
A method for preparation of water dispersible granule given in this example comprises, but not limited to, dissolving cefpodoxime proxetil in a suitable solvent; and granulating the diluent with this solution; and drying and then mixing the granules obtained with potassium clavylanate-syloid (1 :1) and the other excipients which are lubricant, viscosity agent comprising hydroxypropyl cellulose and carboxymethyl cellulose derivative, taste regulating agent, acidic agent, antiadherent and flavouring agent.
EXAMPLE 3: : Formulation and process for preparation of water dispersible tablet
(* ratio of calcium carboxymethyl cellulose: sodium carboxymethyl cellulose is 3:1)
A method for preparation of water dispersible granules given in the example comprises, but not limited to, dissolving cefpodoxime proxetil in a suitable solvent; and granulating the diluent with this solution; and drying and then mixing the obtained granules with the other excipients which are lubricant, viscosity agent comprising hydroxypropyl cellulose, calcium carboxymethyl cellulose and sodium carboxymethyl cellulose, taste regulating agent, acidic agent, antiadherent and flavouring agent.
Claims
1. A pharmaceutical composition comprising cefpodoxime characterized in that;
- said composition comprises hydroxypropyl cellulose and at least one carboxymethyl cellulose derivative agent combination,
- the ratio of carboxymethyl cellulose derivative agent to hydroxypropyl cellulose is in the range of 15 : 1 and 5 : 1 by weight and
- carboxymethyl cellulose derivative agent is selected from carboxymethyl cellulose calcium, carboxymethyl cellulose sodium or a combination thereof.
2. The pharmaceutical composition according to claim 1 , wherein cefpodoxime that is used as the active agent can be in the form of its esters, solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms or in free form and/or a combination thereof.
3. The pharmaceutical composition according to claim 1 and 2, wherein cefpodoxime proxetil is used as the active agent.
4. The pharmaceutical composition according to claim 1-3, wherein said composition is in the form of water dispersible powder, tablet and or granules; single dose effervescent powder, tablets and/or granules; single dose water dispersible powders, tablets and/or granules; multiple dose powder, tablet and/or granules which are dispersed in water to form suspension; single dose water soluble powder, tablet and/or granules; multiple dose water soluble powder, tablet and/or granules.
5. The pharmaceutical composition according to claim 1-4, wherein said formulation comprises hydroxypropyl cellulose having an average particle size in the range of 5-100 μιη.
6. The pharmaceutical composition according to claim 1-5, wherein said formulation comprises the carboxymethyl cellulose derivative having an average particle size in the range of 10-150 μπι.
7. The pharmaceutical composition according to claim 1-6, wherein said composition further comprises pharmaceutically acceptable excipients in addition to cefpodoxime used as the active agent and viscosity agent composition comprising hydroxypropyl cellulose and at least one carboxymethyl cellulose derivative agent combination.
8. The pharmaceutical composition according to claim 1-7, wherein said composition can comprise binder, lubricant, humectant, antiadherent, disintegrant, diluent, basic agent, acidic agent, taste regulating agent, viscosity agent, flavoring agent, preservative agent and/or effervescent couple in addition to cefpodoxime used as the active agent and viscosity agent composition comprising hydroxypropyl cellulose and at least one carboxymethyl cellulose derivative agent.
9. The pharmaceutical composition according to claim 8, wherein the binder is selected from a group comprising ethyl cellulose, gelatine, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminium silicate, methyl cellulose, povidone or the combination thereof.
10. The pharmaceutical composition according to claim 8, wherein the lubricant is selected from a group comprising calcium stearate, magnesium stearate, polyethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, talc, sodium benzoate or the combination thereof.
1 1. The pharmaceutical composition according to claim 10, wherein talc is used as lubricant.
12. The pharmaceutical composition according to claim 8, wherein the humectant is selected from a group comprising anhydrous sodium sulphate, silica gel and potassium carbonate or a combination thereof.
13. The pharmaceutical composition according to claim 8, wherein the antiadherent is selected from a group comprising talc, corn starch, colloidal silica, L-leucine, sodium sulfate, magnesium stearate and sodium stearate.
14. The pharmaceutical composition according to claim 8, wherein the diluent is selected from a group comprising calcium carbonate, calcium sulphate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulphate, microcrystalline cellulose, lactose, magnesium carbonate, magnesium oxide, maltodextrin, maltose, mannitol, sodium chloride, sorbitol, starch, xylitol or combinations thereof.
15. The pharmaceutical composition according to claim 8, wherein the acidic agent is selected from a group comprising acetic acid, citric acid, lactic acid, malic acid, phosphoric acid, propionic acid, tartaric acid or combinations thereof.
16. The pharmaceutical composition according to claim 15, wherein citric acid is used as acidic agent.
17. The pharmaceutical composition according to claim 8, wherein the taste regulating agent is selected from a group comprising acesulfame, aspartame, dextrose, fructose, glucose, lactitol, maltitol, maltose, sorbitol, saccharine, saccharine sodium, sodium cyclamate, sucralose, sodium chloride, potassium chloride, sucrose, xylitol or combinations thereof.
18. The pharmaceutical composition according to claim 8, wherein the effervescent couple is selected from organic acids such as citric acid, tartaric acid, malic acid, fumaric acid and basic agents such as sodium hydrogen carbonate, sodium carbonate, potassium carbonate and potassium hydrogen carbonate .
19. The pharmaceutical composition according to any of the preceding claims, wherein carboxymethyl cellulose derivative agent is composed of carboxymethyl cellulose calcium and carboxymethyl cellulose sodium combination.
20. The pharmaceutical composition according to claim 19, wherein the ratio of carboxymethyl cellulose calcium to carboxymethyl cellulose sodium is in the range of 5:1 and 1:1 by weight.
21. The pharmaceutical composition according to claim 20, wherein the ratio of carboxymethyl cellulose calcium to carboxymethyl cellulose sodium is in the range of 4:1 and 2:1 by weight.
22. The pharmaceutical composition according to any of the preceding claims, wherein said composition can comprise cefpodoxime in the range of 20-800 mg or its pharmaceutically acceptable esters, salts, hydrates, solvates or a combination thereof in an equal amount.
23. The pharmaceutical composition according to any of the preceding claims, wherein said composition can comprise 5-40% of cefpodoxime or its pharmaceutically acceptable esters, solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms in proportion to total amount of unit dose.
24. The pharmaceutical composition according claims 7-23, wherein said composition can comprise 5-40 % of cefpodoxime and at least one; binder in the range of 0-30%; lubricant in the range of 2-10%; humectant in the range of 0-30%; antiadherent in the range of %1- 10; disintegrant and/or disintegrants in the range of 0-15%; diluent in the range of 35- 60%; basic agent in the range of 0-30%; acidic agent in the range of 0.1-15%; taste regulating agent in the range of 10-30%; viscosity agent in the range of 4-15%; flavoring agent in the range of 0.5-3%; preservative agent in the range of 0-3% and optionally effervescent couple in the range of 0-80% in proportion to the total weight of unit dose amount.
25. The pharmaceutical composition according to any preceding claims, wherein said composition comprises clavulanic acid or derivatives thereof in addition to cefpodoxime as the active agent and viscosity agent composition.
26. The pharmaceutical composition according to claim 25, wherein clavulanic acid 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 a combination thereof.
27. The pharmaceutical composition according to claim 26, wherein potassium clavulanate is used in said composition.
28. A method for preparation of the pharmaceutical composition according to preceding claims, wherein said method comprises granulation of the active agent cefpodoxime proxetil by conventional wet and/or dry granulation methods; or powdering cefpodoxime proxetil and other excipients after mixing them by dry blending method and optionally compressing tablets.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2010/09168 | 2010-11-05 | ||
| TR2010/09168A TR201009168A2 (en) | 2010-11-05 | 2010-11-05 | Water dispersible cefpodoxime proxetil formulations. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2012060786A2 true WO2012060786A2 (en) | 2012-05-10 |
| WO2012060786A3 WO2012060786A3 (en) | 2012-07-26 |
Family
ID=45446166
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/TR2011/000255 WO2012060790A2 (en) | 2010-11-05 | 2011-11-03 | Water dispersible cefpodoxime proxetil formulations |
| PCT/TR2011/000251 WO2012060786A2 (en) | 2010-11-05 | 2011-11-03 | Cefpodoxime proxetil formulations comprising viscosity agent |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/TR2011/000255 WO2012060790A2 (en) | 2010-11-05 | 2011-11-03 | Water dispersible cefpodoxime proxetil formulations |
Country Status (2)
| Country | Link |
|---|---|
| TR (1) | TR201009168A2 (en) |
| WO (2) | WO2012060790A2 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103142506A (en) * | 2013-04-03 | 2013-06-12 | 天津医药集团津康制药有限公司 | Cefpodoxime proxetil granules and preparation method thereof |
| CN103230367A (en) * | 2013-05-07 | 2013-08-07 | 山东罗欣药业股份有限公司 | Cefpodoxime proxetil composition dry suspension and preparation method thereof |
| WO2013151517A1 (en) * | 2012-04-04 | 2013-10-10 | Mahmut Bilgic | Tablet formulations comprising cefpodoxime proxetil and clavulanic acid |
| WO2016088041A1 (en) * | 2014-12-01 | 2016-06-09 | Sun Pharmaceutical Industries Limited | Extended-release cefpodoxime proxetil composition |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0049118A2 (en) | 1980-09-30 | 1982-04-07 | Sankyo Company Limited | Cephalosporin derivatives, their preparation and compositions containing them |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE60205870T2 (en) * | 2001-02-27 | 2006-06-29 | Ranbaxy Laboratories, Ltd. | ORAL PHARMACEUTICAL COMPOSITION OF CEFPODOXIM PROXETIL |
| TW200404550A (en) * | 2002-07-08 | 2004-04-01 | Sankyo Co | Cepharospolin formulation for oral use |
| JP4526247B2 (en) * | 2002-07-08 | 2010-08-18 | 第一三共株式会社 | Oral cephalosporins |
| CN1681497A (en) * | 2002-07-16 | 2005-10-12 | 兰贝克赛实验室有限公司 | Dispersible tablets for oral administration |
| WO2007017895A2 (en) * | 2005-05-05 | 2007-02-15 | Lupin Limited | Stabilized oral pharmaceutical compositions of cephalosporins |
| TR201002878A2 (en) * | 2010-04-13 | 2011-10-21 | Bi̇lgi̇ç Mahmut | Pharmaceutical compositions comprising cefpodoxime proxetil. |
-
2010
- 2010-11-05 TR TR2010/09168A patent/TR201009168A2/en unknown
-
2011
- 2011-11-03 WO PCT/TR2011/000255 patent/WO2012060790A2/en active Application Filing
- 2011-11-03 WO PCT/TR2011/000251 patent/WO2012060786A2/en active Application Filing
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0049118A2 (en) | 1980-09-30 | 1982-04-07 | Sankyo Company Limited | Cephalosporin derivatives, their preparation and compositions containing them |
Cited By (5)
| 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 |
| CN103142506A (en) * | 2013-04-03 | 2013-06-12 | 天津医药集团津康制药有限公司 | Cefpodoxime proxetil granules and preparation method thereof |
| CN103230367A (en) * | 2013-05-07 | 2013-08-07 | 山东罗欣药业股份有限公司 | Cefpodoxime proxetil composition dry suspension and preparation method thereof |
| CN103230367B (en) * | 2013-05-07 | 2014-11-12 | 山东罗欣药业集团股份有限公司 | Cefpodoxime proxetil composition dry suspension and preparation method thereof |
| WO2016088041A1 (en) * | 2014-12-01 | 2016-06-09 | Sun Pharmaceutical Industries Limited | Extended-release cefpodoxime proxetil composition |
Also Published As
| Publication number | Publication date |
|---|---|
| TR201009168A2 (en) | 2012-05-21 |
| WO2012060790A2 (en) | 2012-05-10 |
| WO2012060786A3 (en) | 2012-07-26 |
| WO2012060790A3 (en) | 2012-09-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2528589B1 (en) | Stable efervescent formulations comprising cefaclor | |
| WO2012060788A1 (en) | Formulations of cephalosporins with controlled moisture content | |
| WO2011142731A2 (en) | Formulations comprising a third generation cephalosporin and clavulanic acid | |
| WO2012060786A2 (en) | Cefpodoxime proxetil formulations comprising viscosity agent | |
| WO2012026907A2 (en) | Cefpodoxime proxetil formulations | |
| WO2011142730A1 (en) | Pharmaceutical composition comprising cefixime and clavulanic acid derivative compound | |
| JP4743684B2 (en) | Method for improving dissolution of poorly water-soluble drugs | |
| US20130129791A1 (en) | Preparations of effervescent formulations comprising second and third generation cephalosporin and uses thereof | |
| EP2566449B1 (en) | Pharmaceutical compositions comprising ceftibuten | |
| EP2515860B1 (en) | Improved pharmaceutical compositions comprising cefdinir | |
| WO2011129792A1 (en) | Water dispersible formulations comprising cefpodoxime proxetil | |
| WO2011093828A2 (en) | Solid dosage forms comprising cefprozil | |
| EP2566451B1 (en) | Pharmaceutical compositions comprising cefditoren pivoxil | |
| WO2011093829A1 (en) | Effervescent formulations comprising cefixime and clavulanic acid as active agents | |
| WO2012060787A1 (en) | Oral dosage forms comprising cefdinir and carboxymethyl cellulose calcium | |
| WO2012060791A2 (en) | Production method for pharmaceutical compositions comprising cefdinir | |
| WO2011152805A2 (en) | Pharmaceutical composition comprising cefpodoxime proxetil and clavulanic acid | |
| WO2011139255A2 (en) | Pharmaceutical compositions comprising cefetamet | |
| WO2011152808A1 (en) | Formulation comprising cefpodoxime proxetil and clavulanic acid | |
| WO2012026908A2 (en) | Cefpodoxime proxetil formulations comprising taste regulating agent | |
| WO2013109230A1 (en) | Pharmaceutical compositions comprising tadalafil | |
| WO2011093821A1 (en) | Effervescent formulations comprising cefdinir and clavulanic acid | |
| WO2012060792A1 (en) | Pharmaceutical compositions comprising minimum 6 % of disintegrants by weight | |
| WO2012060793A2 (en) | Process for the preparation of cefdinir formulations | |
| EP2833873A1 (en) | Film tablet formulations comprising cefuroxime axetil and clavulanic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 11805268 Country of ref document: EP Kind code of ref document: A2 |
|
| NENP | Non-entry into the national phase in: |
Ref country code: DE |
|
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 11805268 Country of ref document: EP Kind code of ref document: A2 |