WO2011139255A2 - Pharmaceutical compositions comprising cefetamet - Google Patents
Pharmaceutical compositions comprising cefetamet Download PDFInfo
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- WO2011139255A2 WO2011139255A2 PCT/TR2011/000133 TR2011000133W WO2011139255A2 WO 2011139255 A2 WO2011139255 A2 WO 2011139255A2 TR 2011000133 W TR2011000133 W TR 2011000133W WO 2011139255 A2 WO2011139255 A2 WO 2011139255A2
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- 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
- A61K31/4164—1,3-Diazoles
- A61K31/4174—Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0007—Effervescent
Definitions
- the present invention relates to pharmaceutical compositions comprising cefetamet or any pharmaceutically acceptable derivative thereof, and the use of said compositions in the treatment of bacterial infections.
- Cefetamet which has the chemical name (6R,7R)-7-[[(2Z)-2-(2-amino-4- thiazolyl)(methoxyimino)acetyl] amino] -3 -methyl- 8-oxo-5 -thia- 1 -azabicyclo [4.2.0]
- oct-2-ene- 2-carboxylic acid is a third generation cephalosporin antibiotic that has a perfect effect particularly on the species streptococcus, enterobacter, neisseria, hemophilus. It was first disclosed in the patent numbered US4396681 and its strong effect on gram positive and gram negative bacteria was indicated in that patent document.
- Cefetamet is more durable against the enzyme beta-lactamase compared to penicillin, first and second generation cephalosporins.
- the formulation comprising the active agent cefetamet is marketed in 250 mg and 500 mg oral tablet forms.
- the tablet forms comprising 250 and 500 mg active agent in a single dose are formulated with excipients, they become quite large in size and this made the use of this dosage form inconvenient in patients with dysphagia, particularly in pediatric and geriatric patients.
- suspension forms have been developed to overcome said problems in the prior art.
- the patent application numbered in CN 1650868 discloses a medicine in the form of oral liquid or suspension for treating pulmonary infectious diseases which is prepared from ambroxol hydrochloride and one of cefixime, cefetamet sodium and cefetamet hydrochloride.
- suspension forms comprising cefetamet are not preferred since they have the potential of high and/or uncontrolled dose intake and are not physically and chemically stable.
- Cefetamet has a low solubility in water. For that reason, it is generally observed that water dispersible formulations comprising cefetamet cannot quickly disperse since cefetamet cannot dissolve in water entirely. Accordingly, the desirable amount of cefetamet cannot be absorbed and this leads to low bioavailability of it.
- the inventors have surprisingly found that the water dispersible dosage forms comprising cefetamet and its any pharmaceutically acceptable derivative pertaining to the present invention overcome the problems encountered in the prior art.
- the present invention relates to the water dispersible powder, tablet and granules comprising cefetamet and/or pharmaceutically acceptable salts, hydrates, solvates, esters, amorphous and crystal forms of cefetamet and/or combination thereof; their formulations and the procedures for their preparation.
- cefetamet in which d 50 value of the molecule cefetamet is in the range of 10-50 ⁇ solubility problem of cefetamet can be overcome and the formulation comprising it can disperse entirely and quickly.
- the inventors have found that the water dispersible formulations comprising cefetamet in which d 0 value of the cefetamet is in the range of 10-50 ⁇ , has increased solubility of cefetamet and thus the rapid and entire dispersion of said formulations. This provides the increase of the absorption of cefetamet as the active agent and hence the increase of its bioavailability.
- the first aspect of the present invention is the water dispersible formulations comprising cefetamet wherein d 50 value of the molecule cefetamet is in the range of 10-50 ⁇ .
- water dispersible formulations present in the text comprises effervescent tablets, effervescent granules, effervescent powders, water dispersible tablets, water dispersible powders, water dispersible granules, water soluble tablets, water soluble powders and water soluble granules.
- the formulation pertaining to the present invention comprises 5-60%, preferably 5-50%, more preferably 10-40% of cefetamet as the active agent or a pharmaceutically acceptable derivative thereof in an amount equivalent to that.
- Cefetamet which is comprised in the water dispersible formulation pertaining to the present invention, can be in the form of its pharmaceutically acceptable hydrates, solvates, esters, enantiomers, polymorphs, crystal forms, amorphous forms, salts or in free base form and/or a combination thereof.
- Cefetamet comprised in the water dispersible formulation pertaining to the present invention is in ester form. It is preferably cefetamet pivoxil.
- Cefetamet pivoxil comprised in the water dispersible formulation pertaining to the present invention is preferably in salt form. It is preferably cefetamet pivoxil hydrochloride.
- another aspect of the present invention is the water dispersible formulations comprising cefetamet pivoxil hydrochloride wherein d 50 value of the molecule cefetamet pivoxil hydrochloride is in the range of 10-50 ⁇ .
- the water dispersible formulation pertaining to the present invention can comprise one or more of the excipients including binders, lubricants, disintegrants, diluents, flavoring agents, sweeteners, coloring agents, surfactants, anti-foam agent, stabilizing agents, viscosity agents in addition to the cefetamet.
- excipients including binders, lubricants, disintegrants, diluents, flavoring agents, sweeteners, coloring agents, surfactants, anti-foam agent, stabilizing agents, viscosity agents in addition to the cefetamet.
- the lubricant that is used in the pharmaceutical formulation of the present invention can be selected from, but not limited to, a group comprising talc, magnesium stearate, stearic acid, sodium stearil fumarate, polyoxyethylene glycol, leucine, alanine, glycine, sodium benzoate, sodium acetate, fumaric acid or a combination thereof.
- the present invention relates to water dispersible dosage formulations comprising cefetamet wherein the amount of lubricant used is in the range of 1 - 8% by weight.
- the ratio of cefetamet to lubricant is an important parameter on both dissolution and flowability of the formulations. It is observed that the desired flowability and solubility can be provided in the case that the ratio of cefetamet to lubricant is in the range of 20:1 to 1 :1, preferably 15:1 to 2:1, more preferably 10:1 to 5: 1 by weight.
- the present invention relates to water dispersible dosage formulations comprising cefetamet wherein the ratio of cefetamet to lubricant is in the range of 20:1 to 1 : 1 by weight.
- the effervescent acid that is optionally used in the water dispersible formulations pertaining to the present invention can be selected from, but not limited to, a group comprising acetic acid, citric acid, lactic acid, malic acid, phosphoric acid, propionic acid, tartaric acid or a combination thereof.
- the effervescent base that is optionally used in the water dispersible formulations pertaining to the present invention can be selected from, but not limited to, a group comprising potassium carbonate, potassium bicarbonate, potassium citrate, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate, sodium hydrogen citrate or a combination thereof.
- the binder that is used in the pharmaceutical formulation of the present invention can be selected from, but not limited to, a group comprising starches such as potato starch, corn starch, wheat starch; sugars such as sucrose, glucose, dextrose, lactose, maltodextrin; natural and synthetic gums; gelatin; cellulose derivatives such as microcrystalline cellulose, HPC, HEC, HPMC, carboxymethyl cellulose, methyl cellulose, ethyl cellulose; polyvinylpyrrolidone (povidone), polyethylene glycol (PEG); waxes; calcium carbonate; calcium phosphate; alcohols such as sorbitol, xylitol, mannitol, and water or a combination thereof.
- starches such as potato starch, corn starch, wheat starch
- sugars such as sucrose, glucose, dextrose, lactose, maltodextrin
- natural and synthetic gums such as cellulose derivatives such as microcrystalline cellulose, HPC, H
- the disintegrant that is used in the pharmaceutical formulation of the present invention can be selected from, but not limited to, a group comprising starches such as potato starch, corn starch, wheat starch, pregelatinized starch, sodium starch glycolate; cellulose derivatives such as croscarmellose sodium or microcrystalline cellulose; polyvinylpyrrolidone; crospovidone; alginic acid and its salts; clays such as xanthan gum or Veegum; ion exchange resins or a combination thereof.
- starches such as potato starch, corn starch, wheat starch, pregelatinized starch, sodium starch glycolate
- cellulose derivatives such as croscarmellose sodium or microcrystalline cellulose
- polyvinylpyrrolidone such as crospovidone
- alginic acid and its salts such as xanthan gum or Veegum
- ion exchange resins or a combination thereof such as xanthan gum or Veegum
- the diluent that is used in the pharmaceutical formulation of the present invention can be selected from, but not limited to, a group lactose, maltose, dextrin, maltodextrin, mannitol, sorbitol, starch or a combination thereof.
- the flavoring agent that is used in the pharmaceutical formulation of the present invention can be selected from, but not limited to, a group comprising natural aroma oils (peppermint oil, wintergreen oil, clove bud oil, parsley oil, eucalyptus oil, lemon oil, orange oil), menthol, eucalyptol, cinnamon, 1 -methyl acetate, sage, eugenol, oxanone, lemon, orange, blackberry, propenyl guaetol acetyl, cinnamon, vanilla, thymol, linalool or a combination thereof.
- natural aroma oils peppermint oil, wintergreen oil, clove bud oil, parsley oil, eucalyptus oil, lemon oil, orange oil
- menthol eucalyptol
- cinnamon 1 -methyl acetate
- sage eugenol
- oxanone lemon, orange
- blackberry propenyl guaetol acetyl
- cinnamon vanilla
- the sweetener that is used in the pharmaceutical formulation of the present invention can be selected from, but not limited to, a group comprising sucralose, sucrose, fructose, glucose, galactose, xylose, dextrose, laevulose, lactose, maltose, maltodextrin, mannitol, maltitol, maltol, sorbitol, xylitol, erythritol, lactitol, isomalt, corn syrup, saccharine, saccharine salts, acesulfame potassium, aspartame, D-tryptophane, monoammonium glycyrrhizinate, neohesperidin dihydrochalcone, thaumatin, neotame, alitame, stevioside and cyclamates or a combination thereof.
- the viscosity agent that is used in the pharmaceutical formulation of the present invention can be selected from, but not limited to, a group comprising carboxymethyl cellulose, methyl cellulose, xanthan gum, gummi tragacanthae, gum arabic, aerosil 200, collidone, agar-agar, bentonite, hydroxyethyl cellulose or a combination thereof.
- the formulation in water dispersible form pertaining to the present invention comprises; cefetamet in the range of 5-60% by weight
- disintegrant in the range of 0- 10% by weight
- binder in the range of 0-20% by weight.
- the pharmaceutical composition of the present invention can be prepared through a process which is comprised of dry blending or dry granulation or wet granulation of the components or a combination thereof and generally known standard techniques and manufacture procedures in technology.
- the present invention relates to the use of water dispersible dosage forms comprising cefetamet or its any pharmaceutically acceptable derivative in the treatment of the infections caused by gram negative and gram positive bacteria.
- the present invention relates to the use of the pharmaceutical compositions in water dispersible dosage forms comprising cefetamet or any pharmaceutically acceptable derivative thereof in the manufacture 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
- Example 1 Formulation and process for the preparation of effervescent powder, granules or tablets
- the process in scope of the present invention comprises granulating a mixture comprising effervescent couple and sweetener with the granulation solution comprising binder and a solvent through conventional wet and/or dry granulation methods, then sieving the mixture; adding cefetamet pivoxil hydrochloride, lubricant and other excipients into the obtained granules, and optionally compressing the obtained mixture in tablet compressing machine.
- Example 2 Formulation and process for the preparation of water dispersible powder, granules or tablets
- the process in scope of the present invention comprises granulating a mixture comprising cefetamet and binder and the other excipients with the granulation solution comprising the diluent through conventional wet and/or dry granulation methods, then sieving the mixture; adding sweetener and the lubricant into the obtained granules, and optionally compressing the obtained mixture in tablet compressing machine.
Abstract
The present invention relates to pharmaceutical compositions comprising cefetamet pharmaceutically acceptable derivative thereof and process for the preparation of them.
Description
PHARMACEUTICAL COMPOSITIONS COMPRISING CEFETAMET
The present invention relates to pharmaceutical compositions comprising cefetamet or any pharmaceutically acceptable derivative thereof, and the use of said compositions in the treatment of bacterial infections.
Cefetamet, which has the chemical name (6R,7R)-7-[[(2Z)-2-(2-amino-4- thiazolyl)(methoxyimino)acetyl] amino] -3 -methyl- 8-oxo-5 -thia- 1 -azabicyclo [4.2.0] oct-2-ene- 2-carboxylic acid, is a third generation cephalosporin antibiotic that has a perfect effect particularly on the species streptococcus, enterobacter, neisseria, hemophilus. It was first disclosed in the patent numbered US4396681 and its strong effect on gram positive and gram negative bacteria was indicated in that patent document.
Cefetamet is more durable against the enzyme beta-lactamase compared to penicillin, first and second generation cephalosporins.
The formulation comprising the active agent cefetamet is marketed in 250 mg and 500 mg oral tablet forms.
However, in the case that the tablet forms comprising 250 and 500 mg active agent in a single dose are formulated with excipients, they become quite large in size and this made the use of this dosage form inconvenient in patients with dysphagia, particularly in pediatric and geriatric patients.
Alternatively, the suspension forms have been developed to overcome said problems in the prior art. For instance, the patent application numbered in CN 1650868 discloses a medicine in the form of oral liquid or suspension for treating pulmonary infectious diseases which is
prepared from ambroxol hydrochloride and one of cefixime, cefetamet sodium and cefetamet hydrochloride.
However, the suspension forms comprising cefetamet are not preferred since they have the potential of high and/or uncontrolled dose intake and are not physically and chemically stable.
Cefetamet has a low solubility in water. For that reason, it is generally observed that water dispersible formulations comprising cefetamet cannot quickly disperse since cefetamet cannot dissolve in water entirely. Accordingly, the desirable amount of cefetamet cannot be absorbed and this leads to low bioavailability of it.
As is seen, new formulations comprising cefetamet are required to be developed in order to provide new dosage forms which are easily administered and which disperse quickly by providing the entire dissolution of cefetamet in water.
The inventors have surprisingly found that the water dispersible dosage forms comprising cefetamet and its any pharmaceutically acceptable derivative pertaining to the present invention overcome the problems encountered in the prior art.
Description of the Invention:
The present invention relates to the water dispersible powder, tablet and granules comprising cefetamet and/or pharmaceutically acceptable salts, hydrates, solvates, esters, amorphous and crystal forms of cefetamet and/or combination thereof; their formulations and the procedures for their preparation. Surprisingly, it has been found that in the water dispersible formulations comprising cefetamet in which d50 value of the molecule cefetamet is in the range of 10-50 μιτι solubility problem of cefetamet can be overcome and the formulation comprising it can disperse entirely and quickly.
Surprisingly, the inventors have found that the water dispersible formulations comprising cefetamet in which d 0 value of the cefetamet is in the range of 10-50 μηι, has increased solubility of cefetamet and thus the rapid and entire dispersion of said formulations. This provides the increase of the absorption of cefetamet as the active agent and hence the increase of its bioavailability.
According to this, the first aspect of the present invention is the water dispersible formulations comprising cefetamet wherein d50 value of the molecule cefetamet is in the range of 10-50 μηι.
The term "water dispersible formulations" present in the text comprises effervescent tablets, effervescent granules, effervescent powders, water dispersible tablets, water dispersible powders, water dispersible granules, water soluble tablets, water soluble powders and water soluble granules.
The formulation pertaining to the present invention comprises 5-60%, preferably 5-50%, more preferably 10-40% of cefetamet as the active agent or a pharmaceutically acceptable derivative thereof in an amount equivalent to that.
Cefetamet, which is comprised in the water dispersible formulation pertaining to the present invention, can be in the form of its pharmaceutically acceptable hydrates, solvates, esters, enantiomers, polymorphs, crystal forms, amorphous forms, salts or in free base form and/or a combination thereof.
Cefetamet comprised in the water dispersible formulation pertaining to the present invention is in ester form. It is preferably cefetamet pivoxil.
Cefetamet pivoxil comprised in the water dispersible formulation pertaining to the present invention is preferably in salt form. It is preferably cefetamet pivoxil hydrochloride.
Accordingly, another aspect of the present invention is the water dispersible formulations comprising cefetamet pivoxil hydrochloride wherein d50 value of the molecule cefetamet pivoxil hydrochloride is in the range of 10-50 μηι.
The water dispersible formulation pertaining to the present invention can comprise one or more of the excipients including binders, lubricants, disintegrants, diluents, flavoring agents, sweeteners, coloring agents, surfactants, anti-foam agent, stabilizing agents, viscosity agents in addition to the cefetamet.
The lubricant that is used in the pharmaceutical formulation of the present invention can be selected from, but not limited to, a group comprising talc, magnesium stearate, stearic acid, sodium stearil fumarate, polyoxyethylene glycol, leucine, alanine, glycine, sodium benzoate, sodium acetate, fumaric acid or a combination thereof.
In addition to the dissolution problems of the water dispersible formulation comprising cefetamet, some parameters changing according to the formulation developed such as flowability should be taken into consideration during the preparation of the formulations. The inventors have conducted studies on various amounts of lubricant in order to overcome the
flowability problem during the preparation of the water dispersible tablet and granules and they have found that the required flowability is provided when the lubricant is used in the range of 1-8%, preferably 1-6%, more preferably 1-3% by weight.
According to this aspect, the present invention relates to water dispersible dosage formulations comprising cefetamet wherein the amount of lubricant used is in the range of 1 - 8% by weight.
The inventors have also found that the ratio of cefetamet to lubricant is an important parameter on both dissolution and flowability of the formulations. It is observed that the desired flowability and solubility can be provided in the case that the ratio of cefetamet to lubricant is in the range of 20:1 to 1 :1, preferably 15:1 to 2:1, more preferably 10:1 to 5: 1 by weight.
According to this aspect, the present invention relates to water dispersible dosage formulations comprising cefetamet wherein the ratio of cefetamet to lubricant is in the range of 20:1 to 1 : 1 by weight.
The effervescent acid that is optionally used in the water dispersible formulations pertaining to the present invention can be selected from, but not limited to, a group comprising acetic acid, citric acid, lactic acid, malic acid, phosphoric acid, propionic acid, tartaric acid or a combination thereof.
The effervescent base that is optionally used in the water dispersible formulations pertaining to the present invention can be selected from, but not limited to, a group comprising potassium carbonate, potassium bicarbonate, potassium citrate, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate, sodium hydrogen citrate or a combination thereof.
The binder that is used in the pharmaceutical formulation of the present invention can be selected from, but not limited to, a group comprising starches such as potato starch, corn starch, wheat starch; sugars such as sucrose, glucose, dextrose, lactose, maltodextrin; natural and synthetic gums; gelatin; cellulose derivatives such as microcrystalline cellulose, HPC, HEC, HPMC, carboxymethyl cellulose, methyl cellulose, ethyl cellulose; polyvinylpyrrolidone (povidone), polyethylene glycol (PEG); waxes; calcium carbonate; calcium phosphate; alcohols such as sorbitol, xylitol, mannitol, and water or a combination thereof.
The disintegrant that is used in the pharmaceutical formulation of the present invention can be selected from, but not limited to, a group comprising starches such as potato starch, corn starch, wheat starch, pregelatinized starch, sodium starch glycolate; cellulose derivatives such as croscarmellose sodium or microcrystalline cellulose; polyvinylpyrrolidone; crospovidone; alginic acid and its salts; clays such as xanthan gum or Veegum; ion exchange resins or a combination thereof.
The diluent that is used in the pharmaceutical formulation of the present invention can be selected from, but not limited to, a group lactose, maltose, dextrin, maltodextrin, mannitol, sorbitol, starch or a combination thereof.
The flavoring agent that is used in the pharmaceutical formulation of the present invention can be selected from, but not limited to, a group comprising natural aroma oils (peppermint oil, wintergreen oil, clove bud oil, parsley oil, eucalyptus oil, lemon oil, orange oil), menthol, eucalyptol, cinnamon, 1 -methyl acetate, sage, eugenol, oxanone, lemon, orange, blackberry, propenyl guaetol acetyl, cinnamon, vanilla, thymol, linalool or a combination thereof.
The sweetener that is used in the pharmaceutical formulation of the present invention can be selected from, but not limited to, a group comprising sucralose, sucrose, fructose, glucose, galactose, xylose, dextrose, laevulose, lactose, maltose, maltodextrin, mannitol, maltitol, maltol, sorbitol, xylitol, erythritol, lactitol, isomalt, corn syrup, saccharine, saccharine salts, acesulfame potassium, aspartame, D-tryptophane, monoammonium glycyrrhizinate, neohesperidin dihydrochalcone, thaumatin, neotame, alitame, stevioside and cyclamates or a combination thereof.
The viscosity agent that is used in the pharmaceutical formulation of the present invention can be selected from, but not limited to, a group comprising carboxymethyl cellulose, methyl cellulose, xanthan gum, gummi tragacanthae, gum arabic, aerosil 200, collidone, agar-agar, bentonite, hydroxyethyl cellulose or a combination thereof.
According to the present invention, the formulation in water dispersible form pertaining to the present invention comprises; cefetamet in the range of 5-60% by weight
lubricant in the range of 1 -8% by weight
- effervescent couple in the range of 0-80% by weight
- diluent in the range of 0-60% by weight
viscosity agent in the range of 0-5 % by weight
disintegrant in the range of 0- 10% by weight
binder in the range of 0-20% by weight.
- sweetener in the range of 1 -5%
The pharmaceutical composition of the present invention can be prepared through a process which is comprised of dry blending or dry granulation or wet granulation of the components or a combination thereof and generally known standard techniques and manufacture procedures in technology.
In one aspect, the present invention relates to the use of water dispersible dosage forms comprising cefetamet or its any pharmaceutically acceptable derivative in the treatment of the infections caused by gram negative and gram positive bacteria.
According to another aspect, the present invention relates to the use of the pharmaceutical compositions in water dispersible dosage forms comprising cefetamet or any pharmaceutically acceptable derivative thereof in the manufacture 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.
Example 1 Formulation and process for the preparation of effervescent powder, granules or tablets
According to this, the process in scope of the present invention comprises granulating a mixture comprising effervescent couple and sweetener with the granulation solution comprising binder and a solvent through conventional wet and/or dry granulation methods,
then sieving the mixture; adding cefetamet pivoxil hydrochloride, lubricant and other excipients into the obtained granules, and optionally compressing the obtained mixture in tablet compressing machine.
Example 2 Formulation and process for the preparation of water dispersible powder, granules or tablets
According to this, the process in scope of the present invention comprises granulating a mixture comprising cefetamet and binder and the other excipients with the granulation solution comprising the diluent through conventional wet and/or dry granulation methods, then sieving the mixture; adding sweetener and the lubricant into the obtained granules, and optionally compressing the obtained mixture in tablet compressing machine.
Claims
1. The water dispersible formulation comprising cefetamet or any pharmaceutically acceptable derivative thereof characterized in that d50 value of the molecule cefetamet is in the range of 10-50 μηι.
2. The formulation according to claim 1 wherein said formulation comprises 5-60% of cefetamet by weight.
3. The formulation according to claim 1 wherein active agent cefetamet is in the form of its pharmaceutically acceptable hydrates, solvates, esters, enantiomers, polymorphs, crystal forms, amorphous forms, salts or in free base form and/or a combination thereof.
4. The formulation according to claim 3 characterized in that the active agent cefetamet is in ester and/or salt form.
5. The formulation according to claim 4 characterized in that the active agent cefetamet is cefetamet pivoxil.
6. The formulation according to claim 5 characterized in that the active agent cefetamet is cefetamet pivoxil hydrochloride.
7. The formulation according to claim 1 wherein said formulation comprises pharmaceutically acceptable excipients in addition to the active agent cefetamet.
8. The formulation according to claim 7 wherein said formulation comprises one or more of the excipients including binders, lubricants, optionally effervescent couple, glidants, diluents, disintegrants, flavoring agents, sweeteners, coloring agents, surfactants, anti- foam agents, stabilizing agents.
9. The formulation according to claim 8 wherein that the lubricant is selected from a group comprising talc, magnesium stearate, stearic acid, sodium stearyl fumarate, polyoxyethylene glycol, leucine, alanine, glycine, sodium benzoate, sodium acetate, fumaric acid or a combination thereof.
10. The formulation according to claim 9 wherein the amount of the lubricant that said formulation comprises is in the range of 1-8%.
11. The formulation according to claim 10 wherein the amount of the lubricant that said formulation comprises is in the range of 1 -6%.
12. The formulation according to claim 11 wherein the amount of the lubricant that said formulation comprises is in the range of 1-3%.
13. The formulation according to claim 9 wherein the ratio of cefetamet to lubricant is in the range of 20: 1 to 1 : 1 by weight.
14. The formulation according to claim 13 wherein the ratio of cefetamet to lubricant is in the range of 15: 1 to 2:1 by weight.
15. The formulation according to claim 14 wherein the ratio of cefetamet to lubricant is in the range of 10: 1 to 5 : 1 by weight.
16. The formulation according to claim 8 wherein the effervescent acid is selected from a group comprising acetic acid, citric acid, lactic acid, malic acid, phosphoric acid, propionic acid, tartaric acid or a combination thereof.
17. The formulation according to claim 8 wherein the effervescent base is selected from a group comprising potassium carbonate, potassium bicarbonate, potassium citrate, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate, sodium hydrogen citrate or a combination thereof.
18. The formulation according to claim 8 wherein the binder is selected from a group comprising starches such as potato starch, corn starch, wheat starch; sugars such as sucrose, glucose, dextrose, lactose, maltodextrin; natural and synthetic gums; gelatin; cellulose derivatives such as microcrystalline cellulose, HPC, HEC, HPMC, carboxymethyl cellulose, methyl cellulose, ethyl cellulose; polyvinylpyrrolidone (povidone), polyethylene glycol (PEG); waxes; calcium carbonate; calcium phosphate; alcohols such as sorbitol, xylitol, mannitol, and water or a combination thereof.
19. The formulation according to claim 8 wherein the diluent is selected from a group comprising lactose, maltose, dextrin, maltodextrin, mannitol, sorbitol, starch or a combination thereof.
20. The formulation according to claim 8 wherein the disintegrant is selected from a group comprising starches such as potato starch, corn starch, wheat starch, pregelatinized starch, sodium starch glycolate; cellulose derivatives such as croscarmellose sodium or microcrystalline cellulose; polyvinylpyrrolidone; crospovidone; alginic acid and its salts; clays such as xanthan gum or Veegum; ion exchange resins or a combination thereof.
21. The formulation according to claim 8 wherein the flavoring agent is selected from a group comprising natural aroma oils (peppermint oil, wintergreen oil, clove bud oil, parsley oil, eucalyptus oil, lemon oil, orange oil), menthol, eucalyptol, cinnamon, 1- methyl acetate, sage, eugenol, oxanone, lemon, orange, blackberry, propenyl guaetol acetyl, cinnamon, vanilla, thymol, linalool or a combination thereof.
22. The formulation according to claim 8 wherein the sweetener is selected from a group comprising sucralose, sucrose, fructose, glucose, galactose, xylose, dextrose, laevulose, lactose, maltose, maltodextrin, mannitol, maltitol, maltol, sorbitol, xylitol, erythritol, lactitol, isomalt, corn syrup, saccharine, saccharine salts, acesulfame potassium, aspartame, D-tryptophane, monoammonium glycyrrhizinate, neohesperidin dihydrochalcone, thaumatin, neotame, alitame, stevioside and cyclamates or a combination thereof.
23. The formulation according to claim 8 wherein the viscosity agent is selected from a group comprising carboxymethyl cellulose, methyl cellulose, xanthan gum, gummi tragacanthae, gum arabic, aerosyl 200, collidone, agar-agar, bentonite, hydroxyethyl cellulose or a combination thereof.
24. The formulation according to claim 1, wherein said formulation comprises;
- cefetamet in the range of 5-60% by weight
lubricant in the range of 1 -8% by weight
effervescent couple in the range of 0-80% by weight
- diluent in the range of 0-60% by weight
- viscosity agent in the range of 0-5 % by weight
- disintegrant in the range of 0- 10% by weight
- binder in the range of 0-20% by weight
sweetener in the range of 1 -5%
25. The method for the preparation of a pharmaceutical composition according to claim 1, wherein said method comprises a process of dry blending or dry granulation or wet granulation of the components or a combination thereof, and generally known standard techniques and manufacture procedures in technology.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11724475A EP2566450A2 (en) | 2010-05-04 | 2011-05-02 | Pharmaceutical compositions comprising cefetamet |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR201003545 | 2010-05-04 | ||
| TR2010/03545 | 2010-05-04 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2011139255A2 true WO2011139255A2 (en) | 2011-11-10 |
| WO2011139255A3 WO2011139255A3 (en) | 2012-05-03 |
Family
ID=44201076
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/TR2011/000133 WO2011139255A2 (en) | 2010-05-04 | 2011-05-02 | Pharmaceutical compositions comprising cefetamet |
Country Status (2)
| Country | Link |
|---|---|
| EP (1) | EP2566450A2 (en) |
| WO (1) | WO2011139255A2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013109205A1 (en) * | 2012-01-18 | 2013-07-25 | Mahmut Bilgic | Pharmaceutical tablet formulations comprising cefetamet |
| CN104876947A (en) * | 2015-05-06 | 2015-09-02 | 山东罗欣药业集团股份有限公司 | Cefetamet pivoxil hydrochloride hydrate crystals and dispersible tablet thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4396681A (en) | 1981-06-10 | 1983-08-02 | Essex Chemical Corporation | Process for coating one pot moisture curable coating composition onto non-porous substrate and article |
| CN1650868A (en) | 2004-12-02 | 2005-08-10 | 四川川投医药生物技术有限责任公司 | Compound medicinal preparation for treating pneumonia infection disease and its preparation method |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1319533C (en) * | 2003-09-28 | 2007-06-06 | 东北制药总厂 | Cefetamet pivoxil hydrochloride dispersion dispersion tablets and preparation method |
| CN101612138B (en) * | 2009-07-16 | 2011-02-02 | 浙江亚太药业股份有限公司 | Cefetamet pivoxil hydrochloride capsule and preparation method thereof |
-
2011
- 2011-05-02 EP EP11724475A patent/EP2566450A2/en not_active Withdrawn
- 2011-05-02 WO PCT/TR2011/000133 patent/WO2011139255A2/en active Application Filing
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4396681A (en) | 1981-06-10 | 1983-08-02 | Essex Chemical Corporation | Process for coating one pot moisture curable coating composition onto non-porous substrate and article |
| CN1650868A (en) | 2004-12-02 | 2005-08-10 | 四川川投医药生物技术有限责任公司 | Compound medicinal preparation for treating pneumonia infection disease and its preparation method |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013109205A1 (en) * | 2012-01-18 | 2013-07-25 | Mahmut Bilgic | Pharmaceutical tablet formulations comprising cefetamet |
| WO2013109202A2 (en) * | 2012-01-18 | 2013-07-25 | Mahmut Bilgic | Pharmaceutical compounds comprising cefetamet |
| WO2013109202A3 (en) * | 2012-01-18 | 2014-03-20 | Mahmut Bilgic | Pharmaceutical compounds comprising cefetamet |
| CN104876947A (en) * | 2015-05-06 | 2015-09-02 | 山东罗欣药业集团股份有限公司 | Cefetamet pivoxil hydrochloride hydrate crystals and dispersible tablet thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2011139255A3 (en) | 2012-05-03 |
| EP2566450A2 (en) | 2013-03-13 |
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