EP2515858A1 - Pharmaceutical composition with high purity - Google Patents
Pharmaceutical composition with high purityInfo
- Publication number
- EP2515858A1 EP2515858A1 EP10805547A EP10805547A EP2515858A1 EP 2515858 A1 EP2515858 A1 EP 2515858A1 EP 10805547 A EP10805547 A EP 10805547A EP 10805547 A EP10805547 A EP 10805547A EP 2515858 A1 EP2515858 A1 EP 2515858A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- cefdinir
- formulation according
- sodium
- amount
- agent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—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
Definitions
- Present invention is related to water dispersible pharmaceutical dosage forms comprising cefdinir as active agent and methods for preparation of these.
- Cefdinir molecule which is shown with Formula I was first disclosed in the patent numbered BE897864 and its chemical name is (6R,7R)-7-[[(2Z)-(2-amino-4- thiazolil)(hydroxyimino)acetyl] amino]-3-ethenyl-8-oxo-5-thia-l-azabicyclo[4.2.0]oct-2-en-2- carboxylic acid.
- the molecule, which is a third generation cephalosporin, is indicated for the treatment of several illnesses caused by gram positive and gram negative bacteria.
- Cefdinir which physically appears as a white powder has very poor solubility in common organic solvents such as methanol, ethanol, and acetonitrile and in water. Due to this property there are some problems while developing formulations comprising this molecule and in the bioavailability of the finished product.
- Cefdinir is an antibiotic which has a beta lactam ring in its structure. Beta lactam ring has a structure which disintegrates easily. Therefore, after cefdinir is formulated it decomposes in the formulation and can be converted into undesirable byproducts. This situation decreases the ratio of the active agent in the formulation and causes a decrease in the bio-availibity of the obtained product.
- the product sold in the market under the tradename OMNICEF ® is present in capsule and suspension forms. Clinic studies show that the bioavailability of the suspension product is 120% more than the bioavailability of the product in capsule form.
- suspension forms have higher bioavailability, use of this dosage form especially for pediatric and geriatric patients brings about the possibility of taking high and/or uncontrolled dose. Additionally, the fact that the suspensions have physical and chemical stability problems, they have short shelf life and high production costs and the fact that they cause problems while transporting and use are disadvantageous for the manufacturers. Due to the reasons stated above it is necessary to provide new dosage forms in antibiotic theraphy in order to provide effective dosing, meet patient requirements and to offer different alternatives to patients having special conditions, such as pediatric and geriatric patients.
- the present invention is related to water dispersible pharmaceutical compositions wherein the amount of impurity originating from cefdinir is less than 1%.
- Said compositions are characterized in that their impurity content originating from cefdinir is in an amount less than 1%, preferably 0.8% and more preferably 0.6%.
- the first aspect of the present invention is the water dispersible cefdinir formulations comprising the amount of impurity content originating from cefdinir is at most 1%, preferably 0.8% and more preferably 0.6% with respect to the total weight of the formulation comprising unit dose.
- compositions having impurity content originating from cefdinir in an amount of at most 1%.
- Said compositions can also comprise some pharmaceutically acceptable excipients in addition to cefdinir.
- Said pharmaceutical excipients can be selected from a group of sweeteners, pH regulating agents, preservatives, viscosity agents, glidants, lubricants and flavoring agents.
- Sweeteners that can be used in water dispersible pharmaceutical compositions having impurity content originating from cefdinir in an amount of at most 1%, can be selected from a group comprising acesulfame, aspartamate, dextrose, fructose, glucose, lactitol, maltitol, maltose, sorbitol, saccharide, sodium saccharide, sodium cyclamate, sucralose, sodium chloride, potassium chloride, sucrose, xylitol or combinations thereof.
- pH regulating agent that can be used in water dispersible pharmaceutical compositions having impurity content originating from cefdinir in a ratio of at most 1%, can be selected from a group comprising citric acid, malic acid, tribasic calcium phosphate, monosodium glutamate, potassium citrate, sodium citrate, trisodium citrate, sodium hydroxide, dibasic sodium phosphate, monobasic sodium phosphate or combinations thereof.
- citric acid and/or trisodium citrate more preferably a mixture of the combination of citric acid and trisodium citrate is used.
- the inventors have found that the use of the combination of two agents in the range of 5.5% and 7% has an important effect on decreasing the amount of impurity that is formed.
- Preservative that can be used in water dispersible pharmaceutical compositions having impurity content originating from cefdinir in a ratio of at most 1%, can be selected from a group comprising ascorbic acid, citric acid, malic acid, propionic acid, sodium ascorbate, sodium benzoate or combinations thereof.
- Viscosity agent that can be used in water dispersible pharmaceutical compositions having impurity content originating from cefdinir in a ratio of at most 1%, can be selected from a group comprising carboxymethyl cellulose sodium, carboxymethyl cellulose calcium, chitosan, colloidal silicon dioxide, gelatin, guar gum, ksantan gum, hydroxyethyl cellulose, hydroprophyl cellulose, hydroxymethyl cellulose, hypromellose, maltodextrine, ployvinyl alcohol or combinations thereof.
- Glidant that can be used in water dispersible pharmaceutical compositions having impurity content originating from cefdinir in a ratio of at most 1%, can be selected from a group comprising magnesium silicate, silicon dioxide, starch, talk, tribasic calcium phosphateor combinations thereof.
- silicon dioxide is used as a glidant.
- Lubricant that can be used in water dispersible pharmaceutical compositions having impurity content originating from cefdinir in a ratio of at most 1%, can be selected from a group comprising calcium stearate, magnesium stearate, polyethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, talk, sodium benzoate or combinations thereof.
- the present invention is related to water dispersible pharmaceutical composition
- water dispersible pharmaceutical composition comprising impurity content originating from cefdinir in a ratio of at most 1%, cefdinir as active agent and pH regulating agent, sweetener, viscosity agent, lubricant, preservative as excipient.
- Water dispersible cefdinir formulations of the present invention comprising impurity content originating from cefdinir in a ratio of at most 1% can optionally comprise a second active agent.
- Second active agent is clavulanic acid or pharmaceutically acceptable salts thereof.
- the pharmaceutical composition comprising impurity content originating from cefdinir in a ratio of at most 1%, optionally 50-500 mg of clavulanic acid or its pharmaceutically acceptable salts, hydrates, solvates or a combination thereof in an amount equivalent to that can be used.
- Clavulanic acid and/or derivatives thereof are very sensitive to moisture. Therefore, in the pharmaceutical composition according to the present invention, potasium clavulanate is preferably used together with a desiccant in a ratio of 1 : 1.
- One or more than one of the following substances can be used as a desiccant; silica; colloid silica, for instance colloidal silica anhydrous, Aerosil® 200, magnesium trisilicate, powder cellulose, Cabosil®, magnesium oxide, calcium silicate, Syloid®, starch, microcrystalline cellulose and talc.
- silica for instance colloidal silica anhydrous, Aerosil® 200, magnesium trisilicate, powder cellulose, Cabosil®, magnesium oxide, calcium silicate, Syloid®, starch, microcrystalline cellulose and talc.
- potasium clavulanate is preferably used with syloid or microcrystalline cellulose in a ratio of 1 : 1.
- cefdinir or its pharmaceutically acceptable solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystal and amorphous forms can be present in an amount in the range of 2- 20% with respect to the total weight of the unit dose.
- clavulanic acid in an amount in the range of 0-50% with respect to the total weight of the unit dose or its pharmaceutically acceptable salts, solvates, hydrates or a combination thereof in an amount equivalent to that can be used.
- said composition comprises impurity content originating from cefdinir in a ratio of at most 1%, with respect to the total weight of the unit dose; 2-20% of cefdinir, 0-50% potassium clavulanate, 0.1 -5% lubricant, 0.1-5 % glidant 10-90% sweetener, 0.5-5% pH regulating agent, 0.1-5% preservative, 0.1 -5% viscosity agent and 0.1-10% flavoring agent can be used.
- the water dispersible cefdinir composition comprising impurity content originating from cefdinir in a ratio of at most 1% according to the present invention can be present in water dispersible powder, granule or tablet form.
- the present invention is related to the process that can be used for the preparation of water dispersible cefdinir composition comprising impurity content originating from cefdinir in a ratio of at most 1 %.
- the process of the present invention comprises; granulation of cefdinir used as active agent and clavulanic acid, that is optionally used, or derivatives thereof by wet or dry granulation methods or dry blending of cefdinir, clavulanic acid derivatives and other excipients, optionally compressing them in tablet forms or packing in sachet form, preferably preparing them in sachet form.
- Another aspect of the present invention is the use of the pharmaceutical composition that is prepared according to the present invention for the treatment of infections caused by gram positive and gram negative bacteria.
- Another aspect of the present invention is the use of pharmaceutical formulation prepared according to the invention in the production of the drug to be used in the treatment and prophylaxis of upper respiratory tract infections such that ear, nose, throat, otitis media, sinusitis, tonsillitis, pharyngitis, lower respiratory tract infections such as pyelonephritis, cystitis and urethritis, skin and soft tissue infections such as froncle, pyoderma, impetigo and also gonorrhea and lyme diseases.
- upper respiratory tract infections such that ear, nose, throat, otitis media, sinusitis, tonsillitis, pharyngitis, lower respiratory tract infections such as pyelonephritis, cystitis and urethritis, skin and soft tissue infections such as froncle, pyoderma, impetigo and also gonorrhea and lyme diseases.
- Water dispersible formulations in accordance with the present invention can be prepared according to the following examples provided that they are not limited by these examples.
- EXAMPLE 1 Formulation and process for preparation of water dispersible granules comprising cefdinir
- Water dispersible cefdinir composition comprising impurity content originating from cefdinir in a ratio of at most 1% according to the present invention is produced by mixing cefdinir, sweetener, pH regulating agent and other excipients in amounts given in the example after sieving them with 1.3 mm sieve. Said composition is optionally compressed in tablet or filled in sachets.
- EXAMPLE 2 Formulation and process for preparation of water dispersibie granules comprising cefdinir
- Water dispersibie cefdinir composition comprising impurity content originating from cefdinir in a ratio of at most 1% according to the present invention is produced by mixing cefdinir, sweetener, citric acid, trisodium citrate and other excipients in amounts given in the example and sieving them with 1.3 mm sieve. Said composition is optionally compressed in tablet or filled in sachets.
- EXAMPLE 3 Formulation of the preparation of water dispersibie granules comprising cefdinir and process for preparation
- Water dispersibie cefdinir composition comprising impurity content originating from cefdinir in a ratio of at most 1% according to the present invention is produced by mixing cefdinir, a combination of the mixture of potassium clavulanate : microcrystalline cellulose, sweetener, pH regulating agent and other excipients in amounts given in the example after sieving them with 1.3 mm sieve. Optionally, said composition is compressed in tablet form or filled in sachets.
- EXAMPLE 4 Formulation of the preparation of water dispersible granules comprising cefdinir
- Water dispersible cefdinir composition comprising impurity content originating from cefdinir in a ratio of at most 1% according to the present invention is produced by mixing cefdinir, a combination of the mixture of potassium clavulanate : microcrystalline cellulose, sweetener, citric acid, trisodium citrate and other excipients in amounts given in the example after sieving them with 1.3 mm sieve.
- said composition is compressed in tablet form or filled in sachets.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
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Abstract
Present invention is related to water dispersible pharmaceutical dosage forms comprising cefdinir as active agent and methods for preparation of these.
Description
PHARMACEUTICAL COMPOSITION WITH HIGH PURITY
Present invention is related to water dispersible pharmaceutical dosage forms comprising cefdinir as active agent and methods for preparation of these.
Background of the invention
Cefdinir molecule which is shown with Formula I was first disclosed in the patent numbered BE897864 and its chemical name is (6R,7R)-7-[[(2Z)-(2-amino-4- thiazolil)(hydroxyimino)acetyl] amino]-3-ethenyl-8-oxo-5-thia-l-azabicyclo[4.2.0]oct-2-en-2- carboxylic acid. The molecule, which is a third generation cephalosporin, is indicated for the treatment of several illnesses caused by gram positive and gram negative bacteria.
Formula I
Cefdinir which physically appears as a white powder has very poor solubility in common organic solvents such as methanol, ethanol, and acetonitrile and in water. Due to this property there are some problems while developing formulations comprising this molecule and in the bioavailability of the finished product.
Cefdinir is an antibiotic which has a beta lactam ring in its structure. Beta lactam ring has a structure which disintegrates easily. Therefore, after cefdinir is formulated it decomposes in the formulation and can be converted into undesirable byproducts. This situation decreases the ratio of the active agent in the formulation and causes a decrease in the bio-availibity of the obtained product.
The product sold in the market under the tradename OMNICEF® is present in capsule and suspension forms. Clinic studies show that the bioavailability of the suspension product is 120% more than the bioavailability of the product in capsule form.
Although the suspension forms have higher bioavailability, use of this dosage form especially for pediatric and geriatric patients brings about the possibility of taking high and/or uncontrolled dose. Additionally, the fact that the suspensions have physical and chemical stability problems, they have short shelf life and high production costs and the fact that they cause problems while transporting and use are disadvantageous for the manufacturers.
Due to the reasons stated above it is necessary to provide new dosage forms in antibiotic theraphy in order to provide effective dosing, meet patient requirements and to offer different alternatives to patients having special conditions, such as pediatric and geriatric patients.
The present invention is related to water dispersible pharmaceutical compositions wherein the amount of impurity originating from cefdinir is less than 1%. Said compositions are characterized in that their impurity content originating from cefdinir is in an amount less than 1%, preferably 0.8% and more preferably 0.6%.
Accordingly, the first aspect of the present invention is the water dispersible cefdinir formulations comprising the amount of impurity content originating from cefdinir is at most 1%, preferably 0.8% and more preferably 0.6% with respect to the total weight of the formulation comprising unit dose.
Another aspect of the present invention is water dispersible pharmaceutical compositions having impurity content originating from cefdinir in an amount of at most 1%. Said compositions can also comprise some pharmaceutically acceptable excipients in addition to cefdinir.
Said pharmaceutical excipients can be selected from a group of sweeteners, pH regulating agents, preservatives, viscosity agents, glidants, lubricants and flavoring agents.
Sweeteners, that can be used in water dispersible pharmaceutical compositions having impurity content originating from cefdinir in an amount of at most 1%, can be selected from a group comprising acesulfame, aspartamate, dextrose, fructose, glucose, lactitol, maltitol, maltose, sorbitol, saccharide, sodium saccharide, sodium cyclamate, sucralose, sodium chloride, potassium chloride, sucrose, xylitol or combinations thereof. pH regulating agent, that can be used in water dispersible pharmaceutical compositions having impurity content originating from cefdinir in a ratio of at most 1%, can be selected from a group comprising citric acid, malic acid, tribasic calcium phosphate, monosodium glutamate, potassium citrate, sodium citrate, trisodium citrate, sodium hydroxide, dibasic sodium phosphate, monobasic sodium phosphate or combinations thereof. In said pharmaceutical composition, preferably citric acid and/or trisodium citrate, more preferably a mixture of the combination of citric acid and trisodium citrate is used. The inventors have found that the use of the combination of two agents in the range of 5.5% and 7% has an important effect on decreasing the amount of impurity that is formed. The pH agent combination having acidic character, which is used in this amount, plays an important role in the protection of the stability of beta lactam ring.
Preservative, that can be used in water dispersible pharmaceutical compositions having impurity content originating from cefdinir in a ratio of at most 1%, can be selected from a group comprising ascorbic acid, citric acid, malic acid, propionic acid, sodium ascorbate, sodium benzoate or combinations thereof.
Viscosity agent, that can be used in water dispersible pharmaceutical compositions having impurity content originating from cefdinir in a ratio of at most 1%, can be selected from a group comprising carboxymethyl cellulose sodium, carboxymethyl cellulose calcium, chitosan, colloidal silicon dioxide, gelatin, guar gum, ksantan gum, hydroxyethyl cellulose, hydroprophyl cellulose, hydroxymethyl cellulose, hypromellose, maltodextrine, ployvinyl alcohol or combinations thereof.
Glidant, that can be used in water dispersible pharmaceutical compositions having impurity content originating from cefdinir in a ratio of at most 1%, can be selected from a group comprising magnesium silicate, silicon dioxide, starch, talk, tribasic calcium phosphateor combinations thereof. In the pharmaceutical composition of the present invention, preferably silicon dioxide is used as a glidant.
Lubricant, that can be used in water dispersible pharmaceutical compositions having impurity content originating from cefdinir in a ratio of at most 1%, can be selected from a group comprising calcium stearate, magnesium stearate, polyethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, talk, sodium benzoate or combinations thereof.
In another aspect, the present invention is related to water dispersible pharmaceutical composition comprising impurity content originating from cefdinir in a ratio of at most 1%, cefdinir as active agent and pH regulating agent, sweetener, viscosity agent, lubricant, preservative as excipient.
In water dispersible composition, 20-800 mg of cefdinir or its pharmaceutically acceptable salts, hydrates, solvates or a combination thereof in an amount equivalent to that can be used.
Water dispersible cefdinir formulations of the present invention comprising impurity content originating from cefdinir in a ratio of at most 1% can optionally comprise a second active agent. Second active agent is clavulanic acid or pharmaceutically acceptable salts thereof.
Accordingly, in the pharmaceutical composition comprising impurity content originating from cefdinir in a ratio of at most 1%, optionally 50-500 mg of clavulanic acid or its pharmaceutically
acceptable salts, hydrates, solvates or a combination thereof in an amount equivalent to that can be used.
Clavulanic acid and/or derivatives thereof (for example potasium clavulanate) are very sensitive to moisture. Therefore, in the pharmaceutical composition according to the present invention, potasium clavulanate is preferably used together with a desiccant in a ratio of 1 : 1.
One or more than one of the following substances can be used as a desiccant; silica; colloid silica, for instance colloidal silica anhydrous, Aerosil® 200, magnesium trisilicate, powder cellulose, Cabosil®, magnesium oxide, calcium silicate, Syloid®, starch, microcrystalline cellulose and talc.
In the water dispersible cefdinir composition comprising impurity content originating from cefdinir in a ratio of at most 1% according to the present invention, potasium clavulanate is preferably used with syloid or microcrystalline cellulose in a ratio of 1 : 1.
In the water dispersible cefdinir composition comprising impurity content originating from cefdinir in a ratio of at most 1% according to the present invention, cefdinir or its pharmaceutically acceptable solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystal and amorphous forms can be present in an amount in the range of 2- 20% with respect to the total weight of the unit dose.
In the pharmaceutical composition according to the present invention, clavulanic acid in an amount in the range of 0-50% with respect to the total weight of the unit dose or its pharmaceutically acceptable salts, solvates, hydrates or a combination thereof in an amount equivalent to that can be used.
In the water dispersible cefdinir composition, wherein said composition comprises impurity content originating from cefdinir in a ratio of at most 1%, with respect to the total weight of the unit dose; 2-20% of cefdinir, 0-50% potassium clavulanate, 0.1 -5% lubricant, 0.1-5 % glidant 10-90% sweetener, 0.5-5% pH regulating agent, 0.1-5% preservative, 0.1 -5% viscosity agent and 0.1-10% flavoring agent can be used.
The water dispersible cefdinir composition comprising impurity content originating from cefdinir in a ratio of at most 1% according to the present invention can be present in water dispersible powder, granule or tablet form.
The present invention is related to the process that can be used for the preparation of water dispersible cefdinir composition comprising impurity content originating from cefdinir in a ratio of at most 1 %.
Accordingly, the process of the present invention comprises; granulation of cefdinir used as active agent and clavulanic acid, that is optionally used, or derivatives thereof by wet or dry granulation methods or dry blending of cefdinir, clavulanic acid derivatives and other excipients, optionally compressing them in tablet forms or packing in sachet form, preferably preparing them in sachet form.
Another aspect of the present invention is the use of the pharmaceutical composition that is prepared according to the present invention for the treatment of infections caused by gram positive and gram negative bacteria.
Another aspect of the present invention is the use of pharmaceutical formulation prepared according to the invention in the production of the drug to be used in the treatment and prophylaxis of upper respiratory tract infections such that ear, nose, throat, otitis media, sinusitis, tonsillitis, pharyngitis, lower respiratory tract infections such as pyelonephritis, cystitis and urethritis, skin and soft tissue infections such as froncle, pyoderma, impetigo and also gonorrhea and lyme diseases.
Water dispersible formulations in accordance with the present invention can be prepared according to the following examples provided that they are not limited by these examples.
EXAMPLE 1: Formulation and process for preparation of water dispersible granules comprising cefdinir
Water dispersible cefdinir composition comprising impurity content originating from cefdinir in a ratio of at most 1% according to the present invention is produced by mixing cefdinir, sweetener, pH regulating agent and other excipients in amounts given in the example after sieving them with 1.3 mm sieve. Said composition is optionally compressed in tablet or filled in sachets.
EXAMPLE 2: Formulation and process for preparation of water dispersibie granules comprising cefdinir
Water dispersibie cefdinir composition comprising impurity content originating from cefdinir in a ratio of at most 1% according to the present invention is produced by mixing cefdinir, sweetener, citric acid, trisodium citrate and other excipients in amounts given in the example and sieving them with 1.3 mm sieve. Said composition is optionally compressed in tablet or filled in sachets.
EXAMPLE 3: Formulation of the preparation of water dispersibie granules comprising cefdinir and process for preparation
Water dispersibie cefdinir composition comprising impurity content originating from cefdinir in a ratio of at most 1% according to the present invention is produced by mixing cefdinir, a combination of the mixture of potassium clavulanate : microcrystalline cellulose, sweetener, pH regulating agent and other excipients in amounts given in the example after sieving them with 1.3 mm sieve. Optionally, said composition is compressed in tablet form or filled in sachets.
EXAMPLE 4: Formulation of the preparation of water dispersible granules comprising cefdinir
Water dispersible cefdinir composition comprising impurity content originating from cefdinir in a ratio of at most 1% according to the present invention is produced by mixing cefdinir, a combination of the mixture of potassium clavulanate : microcrystalline cellulose, sweetener, citric acid, trisodium citrate and other excipients in amounts given in the example after sieving them with 1.3 mm sieve. Optionally, said composition is compressed in tablet form or filled in sachets.
Claims
1. A water dispersible pharmaceutical composition comprising cefdinir as an active agent, wherein impurity content originating from cefdinir is in an amount of at most 1%.
2. A water dispersible pharmaceutical composition comprising cefdinir according to claim 1, wherein impurity content originating from cefdinir is in an amount of 0.8 %.
3. A water dispersible pharmaceutical composition comprising cefdinir according to claim 2, wherein impurity content originating from cefdinir is in an amount of less than 0.6 %.
4. A water dispersible cefdinir formulation comprising impurity content originating from cefdinir in an amount of at most 1 % according to claim 1, wherein said composition comprises pharmaceutically acceptable excipients in addition to cefdinir that is used as active agent.
5. A formulation according to claim 4, wherein pharmaceutical excipients are selected from a group of sweeteners, pH regulating agents, preservatives, viscosity agents, glidants, lubricants and flavoring agents.
6. A formulation according to claim 5, wherein sweetener is selected from a group comprising acesulfame, aspartamate, dextrose, fructose, glucose, lactitol, maltitol, maltose, sorbitol, saccharide, sodium saccharide, sodium cyclamate, sucralose, sodium chloride, potassium chloride, sucrose, xylitol or combinations thereof.
7. A formulation according to claim 5, wherein pH regulating agent is selected from a group comprising citric acid, malic acid, tribasic calcium phosphate, monosodium glutamate, potassium citrate, sodium citrate, trisodium citrate, sodium hydroxide, dibasic sodium phosphate, monobasic sodium phosphate or combinations thereof.
8. A formulation according claim 7, wherein as pH regulating agent citric acid and/or trisodium citrate is used.
9. A formulation according to claim 8, wherein as pH regulating agent a composition comprising a combination of citric acid and/or trisodium citrate is used.
10. A formulation according claim 7, wherein the amount pH of regulating agent is in an amount in the range of 5.5% and 7% with respect to the total weight of the unit dose.
1 1. A formulation according to claim 9, wherein a composition comprising citric acid and trisodium citrate is used in an amount in the range of 5.5% and 7% with respect to the total weight of the unit dose.
12. A formulation according to claim 5, wherein preservative is selected from a group comprising ascorbic acid, citric acid, malic acid, propionic acid, sodium ascorbate, sodium benzoate or combinations thereof.
13. A formulation according to claim 5, wherein viscosity agent is selected from a group comprising carboxymethyl cellulose sodium, carboxymethyl cellulose calcium, chitosan, colloidal silicon dioxide, gelatin, guar gum, ksantan gum, hydroxyethyl cellulose, hydroprophyl cellulose, hydroxymethyl cellulose, hypromellose, maltodextrine, ployvinyl alcohol or combinations thereof.
14. A formulation according to claim 5, wherein glidant is selected from a group comprising magnesium silicate, silicon dioxide, starch, talk, tribasic calcium phosphateor combinations thereof.
15. A formulation according to claim 14, wherein glidant is silicon dioxide.
16. A formulation according to claim 5, wherein lubricant is selected from a group comprising calcium stearate, magnesium stearate, polyethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, talk, sodium benzoate or combinations thereof.
17. A formulation according to claim 16, wherein lubricant is magnesium stearate.
18. A formulation according to claim 1, wherein 20-800 mg of cefdinir or its pharmaceutically acceptable salts, hydrates, solvates or a combination thereof in an amount equivalent to that is used.
19. A formulation according to claim 1, wherein said formulation optionally comprises a second active agent in addition to cefdinir.
20. A formulation according to claim 19, wherein second active agent is clavulanic acid or pharmaceutically acceptable derivatives thereof.
21. A formulation according to claim 20, wherein clavulanic acid is in the form of its pharmaceutically acceptable salts, preferably in the form of potassium and/or sodium salt.
22. A water dispersible formulation comprising cefdinir as active agent, wherein the impurity content originating from cefdinir is in an amount in the ratio of at most 1% according to any of the previous claims, comprising with respect to the total weight of the unit dose; 2-20% of cefdinir, 0-50% potassium clavulanate, 0.1-5% lubricant, 0.1 -5% glidant, 10-90% sweetener, 0.5-5% pH regulating agent, 0.1-5% preservative, 0.1-5% viscosity agent and 0.1 -10% flavoring agent.
23. A process for the preparation of water dispersible formulation comprising cefdinir as active agent, wherein the impurity content originating from cefdinir is in a ratio of at most 1%, comprises granulation of cefixime, effervescent couple, sweetener and binder with water or an aqueous solution, drying of the formed granules, mixing dried granules with flavoring agent and water soluble lubricant and optionally compressing them in tablet form or packing in sachet form. pharyngitis, lower respiratory tract infections such as pyelonephritis, cystitis and urethritis, skin and soft tissue infections such as froncle, pyoderma, impetigo and also gonorrhea and lyme diseases.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2009/09786A TR200909786A1 (en) | 2009-12-25 | 2009-12-25 | Effervescent tablet and granule formulation containing cefixime. |
| TR201003854 | 2010-05-14 | ||
| PCT/TR2010/000258 WO2011078828A1 (en) | 2009-12-25 | 2010-12-24 | Pharmaceutical composition with high purity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP2515858A1 true EP2515858A1 (en) | 2012-10-31 |
Family
ID=43706441
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP10805547A Withdrawn EP2515858A1 (en) | 2009-12-25 | 2010-12-24 | Pharmaceutical composition with high purity |
Country Status (2)
| Country | Link |
|---|---|
| EP (1) | EP2515858A1 (en) |
| WO (1) | WO2011078828A1 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101420315B1 (en) | 2014-03-19 | 2014-07-17 | 남봉길 | Pharmaceutical liquid composition |
| CN109310774A (en) | 2015-08-17 | 2019-02-05 | 费林股份公司 | Containing can sulfate and magnesium citrate liquid preparation |
| CN107129508B (en) * | 2017-04-19 | 2018-12-07 | 广州牌牌生物科技有限公司 | Cefdinir mixtures of impurities and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA836918B (en) | 1982-09-30 | 1984-05-30 | Fujisawa Pharmaceutical Co | 7-substituted-3-vinyl-3-cephem compounds and processes for the production of the same |
| US20050131079A1 (en) * | 2003-12-10 | 2005-06-16 | Pujara Chetan P. | Cefdinir oral suspension |
| CN1706389A (en) * | 2005-05-26 | 2005-12-14 | 济南平志医药科技有限公司 | Effervescent cefdinir prepn and its prepn process |
| US20070128268A1 (en) * | 2005-12-07 | 2007-06-07 | Herwig Jennewein | Pharmaceutical compositions comprising an antibiotic |
| CN101352424A (en) * | 2008-09-16 | 2009-01-28 | 天津市中央药业有限公司 | Cefdinir dispersible tablet and preparation method thereof |
-
2010
- 2010-12-24 WO PCT/TR2010/000258 patent/WO2011078828A1/en active Application Filing
- 2010-12-24 EP EP10805547A patent/EP2515858A1/en not_active Withdrawn
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| See references of WO2011078828A1 * |
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| Publication number | Publication date |
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| WO2011078828A1 (en) | 2011-06-30 |
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