DESC:The present invention relates to a topical composition comprising of Ozenoxacin and its suitable carrier for making a topical formulation.
The present invention relates to a topical composition of a semi-solid dosage form containing about 0.5% to 10% of the Ozenoxacin composition and a suitable carrier to manufacture a cream or lotion. Preferably, the amount of Ozenoxacin is 0.5% to 2% and more preferably 1%.
According to the embodiments of the present invention, emulsifiers are selected from ethylene glycol monostearate, sorbitan tristearate, a mixture of PEG-6 stearate, glycol stearate and PEG-32 stearate and hydrogenated lecithin, ceto stearyl alcohol.
According to the embodiments of the present invention, surfactants are selected from the mono-olein sorbitan / propylene glycol oleate, Cs / Cw fatty acid mono- and diglycerides from coconut oil, soy lecithin, egg phosphatide, citric acid esters of monoglycerides, monoglyceride lactic acid esters, sucrose fatty acid esters, oleic acid polyglycolated glycerides, linoleic acid polyglycolated glycerides, fatty acid polyglycerol esters, including both long and medium chain fatty acids and these of polyglyceryl fatty acids of mixed fatty acids, and mixtures thereof. Preferably, the surfactants are polyglycolized glycerides of oleic acids, polysorbate 60.
According to the embodiments of the present invention, emollient are selected from white soft paraffin, fatty acids with 8 to 30 carbon atoms, fatty alcohols with 8 to 30 carbon atoms, fatty acid esters with from 8 to 30 carbon atoms, fatty acid amides with 8 to 30 carbon atoms, silicone waxes, and mixtures thereof. Preferably, low melting waxes are fatty alcohols with 8 to 30 carbon atoms. More preferably, a stearyl alcohol is selected from the fatty alcohols.
According to the embodiments of the present invention, water-dispersible or Solubilizer components are selected from polyethylene glycol 400, hexylene glycol, propylene glycol, 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 the use of the compositions of the present invention in the treatment or prevention of skin infections and skin structure in a human or an animal. Therefore, the present invention provides the use of creams and 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, 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 cream 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 cream or lotion can be used by direct application to the affected area.
According to the embodiments of the present invention the topical cream 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, 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 cream. Some embodiments may be directed to a formulation comprising Ozenoxacin and a pharmaceutically acceptable excipient, wherein the formulation is a lotion.
According to one of the preferred embodiments of the present invention relates to topical formulation of Ozenoxacin which is free of emulsifiers selected from the group of ethyleneglycol monostearate, sorbitan tristearate, a mixture of PEG6 stearate, glycol stearate and PEG32 stearate, and hydrogenated lecithin, and mixtures thereof, free of surfactants selected from the group of sorbitan oleate monoolein/propylene glycol, C8/C10 fatty acid mono- and diglycerides from coconut oil, soy lecithin, egg phosphatides, citric acid esters of monoglycerides, lactic acid esters of monoglycerides, diacetyl tartaric acid esters of monoglycerides, succinic acid esters of monoglycerides, sucrose fatty acid esters, polyglycolyzed glycerides of oleic acids, polyglycolyzed glycerides of linoleic acid, polyglycerol esters of fatty acids, and polyglyceryl esters of mixed fatty acids, and mixtures thereof, free of low melting point waxes selected from the group of fatty alcohols having 8 to 30 carbon atoms and mixtures thereof.

The term “Cream” as used herein means semi-solid emulsions of oil and water. They are divided into two types: oil-in-water (O/W) creams which are composed of small droplets of oil dispersed in a continuous water phase, and water-in-oil (W/O) creams which are composed of small droplets of water dispersed in a continuous oily phase. Oil-in-water creams are more comfortable and cosmetically acceptable as they are less greasy and more easily washed off using water. Water-in-oil creams are more difficult to handle but many drugs which are incorporated into creams are hydrophobic and will be released more readily from a water-in-oil cream than an oil-in-water cream. Water-in-oil creams are also more moisturizing as they provide an oily barrier which reduces water loss from the stratum corneum, the outermost layer of the skin.
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.
In the embodiments of the present invention relates to a manufacturing process comprising of dispensing the required quantities of White Soft Paraffin, Ceto Stearyl Alcohol & Polysorbate 60 into the oil phase vessel, heat and stir to obtain a clear solution, add required quantity of benzoic acid into the above mixture and dissolve it and stir, add required quantity of purified water into the water phase vessel and heat to 70 °C under stir, transfer above mixture to manufacturing vessel and add under stirring. Homogenize at 2800 RPM under stirring at 15-25 RPM for 10 minutes at 70 °C weigh required quantity of propylene glycol, heat and separate some quantity into another container for rinsing purpose. take 3/4th quantity of propylene glycol in colloidal mill, add accurately weighed quantity of Ozenoxacin and then mill for 5 - 10 minutes to get uniform dispersion, mix the above process properly and make up the weight of contents of above step with purified water and homogenize the emulsion at 2800 RPM under stirring at 15-25 RPM for 30 minutes at particular temperature, Cool the contents of above step to ~ 25 °C under stirring at 10-25 RPM, Make up the weight of contents of above step with purified water (if required) and recirculate the bulk at least for 10 minutes under stirring at 10-15 RPM.

Example 1:
S.No. Ingredients Category % w/w
1 Ozenoxacin API 1.0
2 Benzoic acid Antimicrobial preservative 0.1
3 Propylene glycol Solubilizer / Humectant 10.0
4 White Soft Paraffin Emollient 2.5
5 Ceto Stearyl Alcohol Stiffening Agent / Emulsifier 10.0
6 Polysorbate 60 Non-Ionic Surfactant / Solubilizing Agent 6.0
7 Purified water Solvent 70.4
Total 100.00

Manufacturing Process:

Oil Phase
i. Add required quantities of White Soft Paraffin, Ceto Stearyl Alcohol & Polysorbate 60 to Oil Phase Vessel. Heat at 70 °C to 75 °C under stirring at 400-600 RPM to obtain a clear solution.
ii. Add required quantity of Benzoic Acid into the step ii and dissolve at 70 °C to 75 °C under stirring at 400-600 RPM.
Aqueous Phase
iii. Add required quantity of Purified Water into Water Phase Vessel and heat at 70 °C to 75 °C under stirring at 400-600 RPM.
Homogenization
iv. Transfer step iii to Manufacturing Phase Vessel and add step ii under stirring. Homogenize at 2800 RPM under stirring at 15-25 RPM for 10 minutes at 70 °C to 75 °C.
Drug Phase
v. Weigh required quantity of Propylene glycol, heat at 50 °C to 55 °C. Add it to colloidal mill and add accurately weighed quantity of Ozenoxacin and then mill for 5 - 10 minutes to get uniform dispersion.
vi. Add contents of step v to contents of step iv.

Make Up and Homogenization
vii. Make up the weight of contents of step vi with purified water and homogenize the emulsion at 2800 RPM under stirring at 15-25 RPM for 30 minutes at 70 °C to 75 °C.
Cooling:
viii. Cool the contents of step vii to ~ 25 °C under stirring at 10-25 RPM.
Make Up and Recirculation
ix. Make up the weight of contents of step viii with purified water (if required) and recirculate the bulk at least for 10 minutes under stirring at 10-15 RPM.
Example 2:
S.No. Ingredients Category % w/w
1 Ozenoxacin API 1.0
2 Benzoic acid Antimicrobial preservative 0.1
3 Propylene glycol Solubilizer / Humectant 10.0
4 White Soft Paraffin Emollient 2.5
5 Stearyl Alcohol Stiffening Agent / Emulsifier 10.0
6 Polysorbate 40 Non-Ionic Surfactant / Solubilizing Agent 6.0
7 Purified water Solvent 70.4
Total 100.00

Manufacturing Process:
Oil Phase
i. Add required quantities of White Soft Paraffin, Stearyl Alcohol & Polysorbate 40 to Oil Phase Vessel. Heat at 70 °C to 75 °C under stirring at 400-600 RPM to obtain a clear solution.
ii. Add required quantity of Benzoic Acid into the step ii and dissolve at 70 °C to 75 °C under stirring at 400-600 RPM.
Aqueous Phase
iii. Add required quantity of Purified Water into Water Phase Vessel and heat at 70 °C to 75 °C under stirring at 400-600 RPM.
Homogenization
iv. Transfer step iii to Manufacturing Phase Vessel and add step ii under stirring. Homogenize at 2800 RPM under stirring at 15-25 RPM for 10 minutes at 70 °C to 75 °C.
Drug Phase
v. Weigh required quantity of Propylene glycol, heat at 50 °C to 55 °C. Add it to colloidal mill and add accurately weighed quantity of Ozenoxacin and then mill for 5 - 10 minutes to get uniform dispersion.
vi. Add contents of step v to contents of step iv.

Make Up and Homogenization
vii. Make up the weight of contents of step vi with purified water and homogenize the emulsion at 2800 RPM under stirring at 15-25 RPM for 30 minutes at 70 °C to 75 °C.
Cooling
viii. Cool the contents of step vii to ~ 25 °C under stirring at 10-25 RPM.
Makeup and Recirculation
ix. Make up the weight of contents of step viii with purified water (if required) and recirculate the bulk at least for 10 minutes under stirring at 10-15 RPM.
,CLAIMS:1. A stable topical composition comprising:

(a) 0.01-2% of Ozenoxacin or its pharmaceutically acceptable salts thereof.

(b) 0.1-1% of Antimicrobial preservative.

(c) 5-15% of Solubilizer.

(d) 1-5% of Emollient.

(e) 5-15% of Emulsifier.

(f) 2-10% of Solubilizing agent.

2. A stable topical composition as claimed in claim 1, wherein the topical pharmaceutical composition is in the form of cream.

3. A stable topical composition as claimed in claim 1, wherein the Antimicrobial preservative is Benzoic acid.

4. A stable topical composition as claimed in claim 1, wherein the Solubilizer is Propylene glycol.

5. A stable topical composition as claimed in claim 1, wherein the Emollient is White soft paraffin.

6. A stable topical composition as claimed in claim 1, wherein the Emulsifier is Ceto stearyl alcohol.

7. A stable topical composition as claimed in claim 1, wherein the Solubilizing Agent is polysorbate 60.

8. A stable topical composition as claimed in claim 1, wherein the composition contain.
a) Free of emulsifiers selected from the group of ethyleneglycol monostearate, sorbitan tristearate, a mixture of PEG6 stearate, glycol stearate and PEG32 stearate, and hydrogenated lecithin, and mixtures thereof;

b) Free of surfactants selected from the group of sorbitan oleate monoolein/propylene glycol, C8/C10 fatty acid mono- and diglycerides from coconut oil, soy lecithin, egg phosphatides, citric acid esters of monoglycerides, lactic acid esters of monoglycerides, diacetyl tartaric acid esters of monoglycerides, succinic acid esters of monoglycerides, sucrose fatty acid esters, polyglycolyzed glycerides of oleic acids, polyglycolyzed glycerides of linoleic acid, polyglycerol esters of fatty acids, and polyglyceryl esters of mixed fatty acids, and mixtures thereof;

c) Free of low melting point waxes selected from the group of fatty alcohols having 8 to 30 carbon atoms and mixtures thereof;

d) Free of Guerbet alcohol 2-octyl dodecanol;

9. A stable topical composition as claimed in claim 1, wherein the composition is used for the treatment of dermatological condition caused by antimicrobial skin infections.

10. A process of preparation of topical dosage form of Ozenoxacin, wherein the oil phase and water phase are Homogenize, Ozenoxacin is added to Propylene glycol and add to the above Homogenized mixture and mixed well to get a uniform dispersion cream.