DESC:The present invention relates to a topical pharmaceutical composition, preparation containing Ozenoxacin or a pharmaceutically acceptable salt thereof. particularly relates to topical lotion pharmaceutical composition
The present invention relates to a topical lotion composition of stable pharmaceutical semi-solid compositions containing from 0.5% to 10% of the Ozenoxacin composition and a suitable carrier to manufacture a lotion. Preferably, the amount of Ozenoxacin is 0.5% to 3% and more preferably 2%.
According to the embodiments of the present invention, water-dispersible or solubilizer components are selected from polyethylene glycol 400, hexylene glycol, propylene glycol, Ethanol, methyl glycol ether, polypropylene glycol-10, ethoxydiglycol, capric / caprylic glyceride polyethylene glycol-6, monobutyl ether ethylene glycol, polyethylene glycol-8, capric / caprylic glycerides, 3-methoxy-3-methyl-1-butanol, dimethyl isosorbide and mixtures thereof. Preferably, the water-dispersible component is propylene glycol.
According to the embodiments of the present invention, antimicrobial preservatives are selected from polyethylene glycol 400, hexylene glycol, propylene glycol, benzoic acid, methyl glycol ether, polypropylene glycol 10, glycol ethoxy, capric / polyethylene glycol 6 caprylic glyceride, monobutyl ether ethylene glycol, polyethylene glycol 8 capric / caprylic glycerides, 3-methoxy-3-methyl-1-butanol, dimethyl isosorbide, and mixtures thereof.
According to the embodiments of the present invention, chelating agent / stabilizer are selected from disodium edetate, ascorbic acid, sodium edetate, sodium thiosulfate, sodium sulfite, sodium pyrosulfite, sodium nitrite, sodium hydrogen sulfite, a photosensitizing dye 201, and the like.
According to the embodiments of the present invention, water soluble polymer are selected from polyoxyethylene polymers such as polyethylene glycol 400, polyethylene glycol 4000, polyethylene glycol 20000, polyethylene glycol 4000000 and polyethylene glycol 600000; polyoxyethylene polyoxypropylene copolymers; acrylic polymers such as sodium polyacrylate, polyethyl acrylate and polyacrylamide; and cellulose derivatives such as methylcellulose, hydrophobized hydroxypropylmethylcellulose, hydroxyethylcellulose, and hydroxypropylcellulose. Cellulose derivatives are preferable, and hydroxyethylcellulose is more preferable.
According to the embodiments of the present invention, buffering agents are selected from metal hydroxides such as sodium hydroxide, potassium hydroxide and lithium hydroxide; hydroxylated lower alkylamines such as monoethanolamine, monoisopropanolamine, diethanolamine, diisopropanolamine, triethanolamine, triisopropanolamine and 2-amino-2-methyl-1,3-propanediol; weak acid metal salts such as sodium bicarbonate, sodium citrate, sodium lactate, disodium hydrogenphosphate, and sodium tartrate; and the like, and preferable are metal hydroxides and weak acid metal salts, and more preferable are potassium hydroxide and sodium bicarbonate.
According to the embodiments of the present invention, pH adjusting agents are selected from metal hydroxides such as sodium hydroxide, potassium hydroxide and lithium hydroxide; hydroxylated lower alkylamines such as monoethanolamine, sodium bicarbonate monoisopropanolamine, diethanolamine, diisopropanolamine, triethanolamine, triisopropanolamine and 2-amino-2-methyl-1,3-propanediol; weak acid metal salts such as sodium bicarbonate, sodium citrate, sodium lactate, disodium hydrogenphosphate, and sodium tartrate; and the like, and preferable are metal hydroxides and weak acid metal salts, and more preferable are potassium hydroxide. These pH adjustors may be used alone or in combination of two or more.
According to the embodiments of the present invention the use of the compositions of the present invention in the treatment or prevention of superficial skin infections and acne accompanied by purulent inflammation human or an animal. Therefore, the present invention provides the use of lotion of the present invention in the treatment or prevention of skin infections and skin structures, with non-limiting examples of such skin infections and skin structures being impetigo, folliculitis, boils, acne, acne accompanied by purulent inflammation, traumatic lesions of secondary forms, superinfected dermatoses, and infected burns of secondary forms, and those infections of the skin and of the skin structures caused by Staphylococcus aureus susceptible to methicillin (SASM), Staphylococcus aureus (SARM), including strains resistant to ciprofloxacin , Methicillin-susceptible Staphylococcus epidermis (SESM), methicillin-resistant Staphylococcus epidermidis (SERM) and Group G Streptococcus pyogenes and Streptococci.
According to the embodiments of the present invention the lotion formulations of certain embodiments herein may also be used as a delivery vehicle for topically administered anti-infective such as, but not limited to, antibiotics, antifungals, antiparasitic, and antiviral agents, corticosteroids, imiquimod or other immune modulating drugs, topical anesthetics, topical chemotherapeutic, or topical photosensitizing agents.
According to the embodiments of the present invention the lotion can be used by direct application to the affected area.
According to the embodiments of the present invention, ethanol is used as solubilizer in the amount of 0.1-10% w/w in the lotion preparation according to the present invention.
According to the embodiments of the present invention, benzoic acid is used as antimicrobial preservatives in the amount of 0.1-2% w/w in the lotion preparation according to the present invention.
According to the embodiments of the present invention, disodium edetate is used as chelating agent / stabilizer in the amount of 0.05-2% w/w in the lotion preparation according to the present invention.
According to the embodiments of the present invention, hydroxy ethyl cellulose is used as water soluble polymer in the amount of 0.60 -2% w/w in the lotion preparation according to the present invention.
According to the embodiments of the present invention, sodium bicarbonate is used as buffering agents in the amount of 0.50 -2% w/w in the lotion preparation according to the present invention.
According to the embodiments of the present invention, potassium hydroxide is used as pH adjusting agents in the amount of 0.50 -2% w/w in the lotion preparation according to the present invention.
According to the embodiments of the present invention the use of the compositions of the present invention in the treatment or prevention of superficial skin infections and acne accompanied by purulent inflammation human or an animal. Therefore, the present invention provides the use of lotion of the present invention in the treatment or prevention of skin infections and skin structures, with non-limiting examples of such skin infections and skin structures being impetigo, folliculitis, boils, acne, acne accompanied by purulent inflammation, traumatic lesions of secondary forms, superinfected dermatoses, and infected burns of secondary forms, and those infections of the skin and of the skin structures caused by Staphylococcus aureus susceptible to methicillin (SASM), Staphylococcus aureus (SARM), including strains resistant to ciprofloxacin , Methicillin-susceptible Staphylococcus epidermis (SESM), methicillin-resistant Staphylococcus epidermidis (SERM) and Group G Streptococcus pyogenes and Streptococci.
According to the embodiments of the present invention the topical lotion provided with suitable carrier contains a mixture of emulsifiers, preservative, surfactants, Solubilizer / humectant, Emollient, Stiffening Agent, Emulsifier, Non-Ionic Surfactant, Solubilizing Agent, oily components, low melting waxes, preservative, stabilizer, water, water-dispersible components and formaldehyde donating preservatives.
According to the embodiments of the present invention the topical formulation is directed to a cosmetically acceptable formulation, comprising Ozenoxacin and pharmaceutically acceptable excipients, wherein the said formulation is a lotion.
According to the embodiments of the present invention relates to a topical pharmaceutical composition containing a pyridonecarboxylic acid derivative or a pharmaceutically acceptable salt thereof, having an antimicrobial activity where in the topical composition is in particularly a lotion preparation.
According to the embodiments of the present invention relates to a stable pharmaceutical semi-solid topical composition of 0.5% to 10% of the Ozenoxacin composition and a suitable carrier to manufacture a lotion. Preferably, the amount of Ozenoxacin is 0.5% to 3% and more preferably 2%.
According to the embodiments of the present invention relates to the lotion formulation which is provided in suitable carrier, which contains one or more anti-microbial preservative, solubilizer, chelating agent / stabilizer, water soluble polymer, solubilizer / solvent, buffering agent, pH adjusting agent and solvent.
According to the embodiments of the present invention is the use of the compositions of the present invention in the treatment or prevention of superficial skin infections and acne accompanied by purulent inflammation.
The term “Lotion” as used herein means semi-solid emulsions of oil and water. They are divided into two types: oil-in-water (O/W) lotion which are composed of small droplets of oil dispersed in a continuous water phase, and water-in-oil (W/O) lotion which are composed of small droplets of water dispersed in a continuous oily phase.
The term “Lotion” as used herein means low-viscosity topical preparation intended for application to the skin. By contrast, creams and gels have higher viscosity, typically due to lower water content.
Example 1:
S. No. Ingredients Category % w/w
1 Ozenoxacin API 2.00
2 Benzoic Acid Anti-Microbial Preservative 0.10
3 Propylene Glycol Solubilizer / Solvent 15.00
4 Disodium Edetate Chelating Agent / Stabilizer 0.05
5 Hydroxy Ethyl Cellulose Water Soluble Polymer 0.60
6 Ethanol Solubilizer / Solvent 5.00
7 Sodium Bicarbonate Buffering Agent 0.50
8 Potassium Hydroxide pH Adjusting Agent 0.60
9 Purified Water Solvent 76.15
Total 100.00

Manufacturing Process:
i. Weigh required quantity of propylene glycol into SS container.
ii. Add required quantity of benzoic acid to step i under stirring at medium speed until clear solution is obtained.
iii. Add required quantity of disodium edetate to step ii under stirring at medium speed until uniform dispersion is obtained.
iv. Slowly add required quantity of hydroxy ethyl cellulose to step iii (avoid formation of lumps) under stirring at medium speed until uniform dispersion is obtained.
v. Add required quantity of sodium bicarbonate to step iv under stirring at medium speed until uniform dispersion is obtained.
vi. Weigh & transfer required quantity of purified water in SS container.
vii. Separate in to 3 SS containers each contains 10% w/w quantity, 10% w/w quantity and 20% w/w quantity of purified water individually from step vi.
viii. Take remaining 60% w/w quantity of purified water to SS manufacturing vessel.
ix. Add contents of step v to step viii under stirring at medium speed to obtain clear liquid.
x. Rinse the container of step v using 10% w/w quantity of purified water (of step vii) and add to step ix under stirring at medium speed. Mix for 30 – 60 minutes.
xi. Add required quantity of ethanol to step x under stirring at medium speed.
xii. Add required amount of Potassium hydroxide to 10% w/w quantity of purified water (of step vii) in another SS container and dissolve completely.
xiii. Add required quantity of Ozenoxacin to step xii and stir well to get clear solution.
xiv. Add contents of step xiii to step xi under stirring at medium speed.
xv. Rinse the container of step xiii using 20% w/w quantity of purified water (of step vii) and add to step xiv under stirring at medium speed.
xvi. Make up the weight of lotion using purified water. Mix for 30 – 60 minutes at medium speed.
xvii. Transfer the lotion from manufacturing vessel to suitable container for storage until packing.

Example 2:
S. No. Ingredients Category % w/w
1 Ozenoxacin API 2.00
2 Benzoic Acid Preservative 0.10
3 Hydroxy Ethyl Cellulose Water Soluble Polymer 1.00
4 Propylene Glycol Solubilizer / Solvent 20.00
5 Potassium Hydroxide pH adjuster 0.60
6 Sodium Bicarbonate pH adjuster 0.50
7 Purified Water Solvent q.s.
Total 100.00

Manufacturing Process:
i. Add required quantity of Benzoic Acid to Propylene Glycol and dissolve under stirring in SS container. Rinse benzoic acid polybag / container using 5% w/w amount of purified water.
ii. Weigh & transfer 40% w/w amount of purified water to step i.
iii. Slowly add required quantity of Hydroxy Ethyl Cellulose to step ii under stirring and stir until clear liquid is obtained.
iv. Add required amount of Potassium hydroxide to 10% w/w amount of purified water in another SS container and dissolve completely.
v. Add required amount of Ozenoxacin to step iv and dissolve completely. Rinse Ozenoxacin polybag / container using 5% w/w amount of purified water.
vi. Add contents of step v to step iii under stirring.
vii. Add required amount of Sodium Bicarbonate to 15% w/w amount of purified water in another SS container and dissolve completely.
viii. Add contents of step vii to step vi under stirring.
ix. Finally, add the remaining amount of purified water to obtain the target lotion.
Check and confirm pH of lotion is in between 10 to 12.

Example 3:
S. No. Ingredients Category % w/w
1 Ozenoxacin API 2.00
2 Benzoic Acid Preservative 0.10
3 Hydroxy Ethyl Cellulose Water Soluble Polymer 1.00
4 Propylene Glycol Solubilizer / Solvent 15.00
5 Ethanol Solubilizer / Solvent 5.00
6 Potassium Hydroxide pH adjuster 0.60
7 Sodium Bicarbonate pH adjuster 0.50
8 Purified Water Solvent q.s.
Total 100.00

Manufacturing Process:
i. Add required quantity of Benzoic Acid to Propylene Glycol & Ethanol and dissolve under stirring in SS container. Rinse benzoic acid polybag / container using 5% w/w amount of purified water.
ii. Weigh & transfer 40% w/w amount of purified water to step i.
iii. Slowly add required quantity of Hydroxy Ethyl Cellulose to step ii under stirring and stir until clear liquid is obtained.
iv. Add required amount of Potassium hydroxide to 10% w/w amount of purified water in another SS container and dissolve completely.
v. Add required amount of Ozenoxacin to step iv and dissolve completely. Rinse Ozenoxacin polybag / container using 5% w/w amount of purified water.
vi. Add contents of step v to step iii under stirring.
vii. Add required amount of Sodium Bicarbonate to 15% w/w amount of purified water in another SS container and dissolve completely.
viii. Add contents of step vii to step vi under stirring.
ix. Finally, add the remaining amount of purified water to obtain the target lotion.
Check and confirm pH of lotion is in between 10 to 12.
,CLAIMS:1. A stable topical lotion composition comprising a Ozenoxacin or its pharmaceutically acceptable salts and one or more pharmaceutically acceptable excipients, where in the Ozenoxacin is present in the amount of 0.2-5% from the total weight of the composition.

2. The stable topical lotion composition as claimed in claim 1, where in the pharmaceutically acceptable excipients are anti-microbial preservative, solubilizer, chelating agent / stabilizer, water soluble polymer, solubilizer / solvent, buffering agent, pH adjusting agent and solvent.

3. The stable topical lotion composition as claimed in claim 1, where in the excipients are benzoic acid, propylene dlycol, disodium edetate, hydroxy ethyl cellulose, ethanol, sodium bicarbonate, potassium hydroxide and combination thereof.

4. The process of preparation of a pharmaceutical composition as claimed in claim 1 involves:
Add benzoic acid to propylene glycol and dissolve, rinse benzoic acid polybag, 40% w/w amount of purified water to above step, add required quantity of hydroxy ethyl cellulose to above step, add required amount of Potassium hydroxide to 10% w/w amount of purified water, add required amount of Ozenoxacin to above step, rinse Ozenoxacin polybag / container, perform stirring, add required amount of Sodium Bicarbonate, add the remaining amount of purified water to obtain the target lotion.

5. The stable topical lotion composition as claimed in claim 1, where in the composition is used for the treatment or prevention of superficial skin infections and acne accompanied by purulent inflammation.