DESC:FIELD OF THE INVENTION
The present invention relates to a topical pharmaceutical composition comprising luliconzole or salts thereof and ketoconazole or salts thereof, its process of preparation and method of use of said pharmaceutical composition.

More particularly, the present invention relates to a topical pharmaceutical composition comprising luliconazole or salts thereof and ketoconazole or salts thereof, its process of preparation and method of use of said pharmaceutical composition in the treatment of fungal infection(s).

BACKGROUND OF THE INVENTION
Luliconazole is an azole antifungal agent. Chemically Luliconazole is (2E)-2-[(4R)-4-(2,4-dichlorophenyl)-1,3-dithiolan-2-ylidene]-2-imidazol-1-ylacetonitrile and its molecular weight is of 354.28. Its empirical formula is C14H9Cl2N3S2. Luliconazole is the R enantiomer and contains one chiral center. The double bond adjacent to the dithiolane group is in the E configuration. Luliconazole is represented by compound of structural formula I

(Formula I)

Luliconazole drug substance is a pale to light yellow crystalline powder. It is low soluble in water and soluble in Acetonitrile, Dimethyl sulfoxide and Methanol.
Luliconazole topical cream (1%) was first approved by U.S. FDA on Nov 14, 2013 under the brand name “Luzu” for Bausch Health US LLC and is indicated for the topical treatment of interdigital tinea pedis, tinea cruris, and tinea corporis caused by the organisms Trichophyton rubrum and Epidermophyton floccosum.

Ketoconazole is an antifungal agent. Chemically ketoconazole is cis-1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl] methoxy]phenyl]piperazine. Its empirical formula is C26H28Cl2N4O4 and its molecular weight is of 531.44. Ketoconazole is represented by compound of structural formula II.

(Formula II)
Ketoconazole topical cream (2%) was first approved by U.S. FDA on Dec 31, 1985 under the brand name “NIZORAL” for Janssen Pharmaceutica Products LP and is indicated for the topical treatment of tinea corporis, tinea cruris and tinea pedis caused by Trichophyton rubrum, T. mentagrophytes and Epidermophyton floccosum; in the treatment of tinea (pityriasis) versicolor caused by Malassezia furfur (Pityrosporum orbiculare); in the treatment of cutaneous candidiasis caused by Candida spp. and in treatment of seborrheic dermatitis.

Further, there are fungal stains which is resistant or become resistant by use of sole active ingredient(s) such as luliconazole or salt thereof or ketoconazole or salt thereof, renders them not efficient in the treatment of topical fungal infection; since alone they do not provide broad spectrum of antifungal activity which is required in topical fungal infection(s).

Thus, there is an unmet need in the art to provide topical antifungal composition comprising one or more antifungal agent, which provides broad spectrum antifungal activity with minimum adverse effects in the treatment of fungal infection(s).

Accordingly, the present invention provides a topical pharmaceutical composition comprising luliconazole or salts thereof and ketoconazole or salts thereof which is not only efficient but has minimum side effects thereby resulting in better patient compliance in the treatment of topical fungal infection(s).

OBJECTS OF THE INVENTION
It is an object of the present invention to provide a topical pharmaceutical composition comprising luliconazole or salts thereof and ketoconazole or salts thereof.

It is another object of the present invention to provide a topical pharmaceutical composition comprising luliconazole or salts thereof and ketoconazole or salts thereof which provide a broad spectrum of activity in the treatment of fungal infection(s).

It is a further object of the present invention to provide a topical pharmaceutical composition comprising luliconazole or salts thereof and ketoconazole or salts thereof which provide minimum side effects in the treatment of fungal infection(s).

It is yet another object of the present invention to provide a topical pharmaceutical composition comprising luliconazole or salts thereof and ketoconazole or salts thereof which is efficacious and provide better patient compliance in the treatment of fungal infection.

SUMMARY OF THE INVENTION
In one aspect, the present invention provides a topical pharmaceutical composition comprising luliconazole or salts thereof and ketoconazole or salts thereof.

In another aspect, the present invention provides a novel topical pharmaceutical composition comprising luliconazole or salts thereof and ketoconazole or salts thereof along with one or more pharmaceutically acceptable excipients.

In another aspect, the present invention provides a process of manufacturing topical pharmaceutical composition comprising luliconazole or salts thereof and ketoconazole or salts thereof along with one or more pharmaceutically acceptable excipients.

In yet another aspect, the present invention provides a topical pharmaceutical composition comprising luliconazole or salts thereof and ketoconazole or salts thereof in the treatment of fungal infection(s).

DETAILED DESCRIPTION OF THE INVENTION

The term "composition" or "pharmaceutical composition" or "topical pharmaceutical composition" as used herein synonymously include dosage forms such as a cream, ointment, gel, paste, liniment, lotion, foam, spray and solution or the like.

The term “composition”, as in “topical pharmaceutical composition”, is intended to encompass a drug product(s) comprising luliconazole or salts thereof and ketoconazole or salts thereof and other inert ingredient(s) (pharmaceutically acceptable excipients).

The present invention relates to a novel topical pharmaceutical composition comprising luliconazole or salts thereof and ketoconazole or salts thereof and at least one pharmaceutically acceptable excipient for topical administration.

The term “Luliconazole” is used in broad sense to include not only “Luliconazole” per se but also its pharmaceutically acceptable salts, solvates, hydrates, enantiomers, derivatives, isomers, polymorphs, prodrugs thereof.

The term “Ketoconazole” is used in broad sense to include not only “Ketoconazole” per se but also its pharmaceutically acceptable salts, solvates, hydrates, enantiomers, derivatives, isomers, polymorphs, prodrugs thereof.

The term “Pharmaceutically acceptable salts” or “salt thereof” as used herein, includes those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, which are well known in the art.

Pharmaceutically acceptable salts include, but are not limited to, any of the salts or cocrystals of luliconazole selected from citrate, hydrochloride, hydrobromide, sulphate, phosphate, maleate, formate, acetate, nitrate, mesylate, succinate, benzoate or the like.

Pharmaceutically acceptable salts include, but are not limited to, any of the salts or cocrystals of ketoconazole selected from citrate, hydrochloride, hydrobromide, sulphate, phosphate, maleate, formate, acetate, nitrate, mesylate, succinate, benzoate or the like.

The term "treating" or "treatment" refers to obtaining desired pharmacological and/or physiological effect. The effect can be therapeutic, which includes achieving, partially or substantially, one or more of the following results: partially or totally reducing the extent of the disease, disorder or syndrome; ameliorating or improving a clinical symptom or indicator associated with the disorder or delaying, inhibiting or decreasing the likelihood of the progression of the disease, disorder or syndrome.

A novel topical pharmaceutical composition comprising luliconazole or salts thereof and ketoconazole or salts thereof, according to present invention provides unique combination of at least two antifungal agents.

In one embodiment, the present invention relates to a novel topical pharmaceutical composition comprising luliconazole or salts thereof and ketoconazole or salts thereof.

In one embodiment, the present invention provides a novel topical pharmaceutical composition, comprising:
a) Luliconazole or salts thereof;
b) Ketoconazole or salts thereof; and
c) One or more suitable pharmaceutically acceptable excipient.

In one embodiment, the present invention provides a process of preparation of a novel topical pharmaceutical composition, comprising:
a) Luliconazole or salts thereof;
b) Ketoconazole or salts thereof; and
c) One or more suitable pharmaceutically acceptable excipient.

In a preferred embodiment, the topical pharmaceutical composition of the present invention comprises Luliconazole and Ketoconazole. The concentration of Luliconzole is at least 0.001%; preferably the concentration ranges from 0.05 to 2%; more preferably the concentration is 1% by weight of composition. The concentration of Ketoconazole is at least 0.05%; preferably the concentration ranges from 0.01 to 3%; more preferably the concentration is 2% by weight of composition.

In another embodiment, the pharmaceutically acceptable excipients are selected from the group consisting of bases, solubilizing or emulsifying agent, preservative, antioxidant, gelling agent, thickening agent, humectant, adsorbent, permeation enhancer, opacifying agent, chelating agent, acidifying or alkalizing or buffering agent and vehicle and any other excipient known to the art for making a novel topical pharmaceutical composition.

The example of bases includes but not limited to Carnauba wax, Cetyl alcohol, Cetyl ester wax, Emulsifying wax, Hydrous lanolin, Lanolin, Lanolin alcohols, Vegetable oils and Animal fat; Coconut oil, Bees wax, Olive oil, Spermaceti wax, Sesame oil, Almond oil, Alcohols, Acids and Esters; oleic acid, Oleyl alcohol, Palmitic acid, Lauryl alcohol, Lauric acid, Myristyl alcohol, Ethyl oleate, Isopropyl myristate, Ethylene glycol, Hydrogenated and Sulphated oils; Hydrogenated castor, Cotton seed, Hydrogenated sulphated castor oils, Microcrystalline wax, Liquid Paraffin, Petrolatum, Propylene glycol, Polyethylene glycol, Stearic acid, Stearyl alcohol and Cetostearyl alcohol. The amount of base present in the composition ranges from about 1-50%; preferably about 2-40%; more preferably about 2-30% by weight of composition.

The examples of solubilizing or emulsifying agent includes but not limited to Polysorbate 20, Polysorbate 80, Polysorbate 60, Poloxamer, Emulsifying wax, Sorbitan monostearate, Sorbitan monooleate, Sodium lauryl sulfate, Propylene glycol monostearate, Natural gums like Acacia and Tragacanth, Monovalent and Bivalent soaps, Lanolin, Cholesterol or Cholesterol esters, Triethanolamine and its salts, Dodecyl benzene sulfonate, Diethylene glycol monoethyl ether and Docusate sodium. The amount of solubilizing or emulsifying agent present in the composition ranges from about 0.05-10%; preferably about 0.1-5%; more preferably about 1-3% by weight of composition.
The example of preservative includes but not limited to Chorocresol, Benzoic acid, Phenyl mercuric nitrate, Benzyl alcohol, Benzoic acid and its salts, Boric acid, Methyl paraben, Propyl paraben, Trihydrate and Anhydrous Sodium Acetate, Chlorhexidine, Formaldehyde, Glutaraldehyde, Imidazolidinyl urea, Trichlosan, Sodium Metabisulfite, Benzalkonium chloride and Chloroxylenol. The amount of preservative present in the composition ranges from about 0.01-5%; preferably about 0.05-2.5%; more preferably about 0.1-1.0% by weight of composition.

The example of antioxidant includes but not limited to Butylated hydroxyl anisole, Butylated hydroxyl toluene, Propyl gallate, Polyols like Sorbitol, Xylitol and Maltitol, natural extracts like Quillaia or lactic acid or urea, Lithium Chloride, Ascorbic acid, Sodium Metabisulfite, Carotinoids, Carotenes such as a-carotene, ß-carotene and Lycopene, Chlorogenic acid, Tocopherols, Uric acid, Zinc oxide (ZnO) and Zinc sulphate (ZnSO4). The amount of antioxidant present in the composition ranges from about 0.01-5%; preferably about 0.01-2.5%; more preferably about 0.01-1.0% by weight of composition.

The example of gelling agent includes but not limited to Carbomer/Carbopols, Pemulen®, cellulose derivatives such as Methyl Cellulose, Hydroxy Ethylcellulose, Hydroxy Propyl methylcellulose, Carboxy methyl cellulose, Hydroxy propyl cellulose, Glycerol or Propylene glycol gelled with suitable agents such as natural gums such as Xanthan gum and Tragacanth, Fenugreek Mucilage, Pectin, Poloxamers (Pluronics), Alginate, Gelatin, Starch, Polyvinyl alcohol, Povidone etc. The amount of gelling agent present in the composition ranges from about 0.01-5%; preferably about 0.1-2.5%; more preferably about 0.25-1.0% by weight of composition.

The examples of thickening agent include but not limited to Carbomer, Hydrogenated castor oil, Methyl cellulose, Sodium carboxyl methyl cellulose, Carrageenan, Colloidal silicon dioxide, Natural gum such as Gelatin, Tragacanth gum and Guar gum, Hydroxypropyl cellulose, Hydroxypropyl methyl cellulose, Polyethylene oxide, Alginic acid, Paraffin, Cetostearyl alcohol, Polyethylene glycol, PEG 200, PEG 300, PEG 400, PEG 600, Monoethanolamine, Triethanolamine, Glycerol, Polyoxyethylene sorbitan monooleate, and Poloxamers, Polyvinyl pyrrolidone, various alcohols such as Polyvinyl alcohol, Ethanol or Isopropyl alcohol and Fumed silica.

The example of humectant includes but not limited to Glycerin, Glyceryl triacetate, Propylene glycol, Polyethylene glycol, Sorbitol solution, 1,2,6 Hexanetriol, Isopropyl myristate, Petrolatum, Isopropyl palmitate, Hydrogenated castor oil, Mineral oil, Polyoxymethylene urea and Potassium sorbate.

The example of adsorbent includes but not limited to Magnesium carbonate, Calcium carbonate, Starch, Cellulose and its derivatives.

The example of Permeation enhancer includes but not limited to Isopropyl myristate, Isopropyl ricinoleate, Propylene glycol, Ethanol, Isopropyl alcohol, Oleic acid, Polyethylene glycol, Phospholipids, Cyclodextrins, Black pepper (Piper nigrum), Pyrrolidones, Dimethyl sulphoxide (DMSO), Decyl methyl sulphoxide (DCMS), Terpenes (Cineole, Eugenol, D-limonene, Menthol, Menthone) and Urea.

The examples of opacifying agent include but not limited to higher fatty alcohols such as Cetyl, Stearyl, Cetostearyl alcohol, Arachidyl and Behenyl alcohols, solid esters such as Cetyl palmitate, Glyceryl laurate, various fatty acid derivatives such as Propylene glycol and Polyethylene glycol esters, inorganic materials such as, Magnesium aluminium silicate, Zinc oxide, Titanium dioxide or other sunblocking agents.

The example of chelating agent includes but not limited to Ethylene diamine tetraacetate, Dimercaprol, Dimercaptosuccinic acid, Penicillamine, Deferoxamine, Deferasirox, Citric acid, Maleic acid, Phosphoric acid and like.

The example of Acidifying or alkalizing or buffering agent includes but not limited to Anhydrous and Monohydrate Citric acid, Phosphoric acid, Sodium hydroxide, Potassium Hydroxide, Sodium Bicarbonate, Potassium sorbate, Monobasic and Dibasic sodium Phosphate and Trolamine.

The example of vehicle includes but not limited to Purified water, Hexylene glycol, Propylene glycol, Oleyl alcohol, Propylene carbonate, Mineral oil, Almond oil, Cottonseed oil, Ethyl oleate, Isopropyl myristate, Isopropyl palmitate, Myristyl alcohol, Octyldodecanol, Olive oil, Peanut oil, Safflower oil, Sesame oil, Soybean oil and Squalene. The amount of vehicle present in the composition ranges from about 10-60%; preferably about 20-50%; more preferably about 30-50% by weight of composition.

The topical pharmaceutical composition of the present invention may be in the form of cream, ointment, gel, paste, lotion and spray for the treatment of topical fungal infections.

In another aspect of present invention is to provide process of preparing topical pharmaceutical composition comprising Luliconazole or salts thereof and Ketoconazole or salts thereof and pharmaceutically acceptable excipients in the treatment of topical fungal infection.

The process of manufacturing topical composition according to present invention involves trituration method, levigation method, fusion method, chemical reaction method or emulsification method.

The manufacturing process involves admixing luliconazole or salts thereof and ketoconazole or salts thereof optionally along with one or more pharmaceutically acceptable excipient to form cream, ointment, gel, paste, lotion and spray.

The topical pharmaceutical composition comprising luliconazole or salts thereof and ketoconazole or salts thereof according to present invention provides broad spectrum antifungal activity with minimum adverse effects in the treatment of fungal infection(s).

A novel topical pharmaceutical composition comprising luliconazole or salts thereof and ketoconazole or salts thereof according to present invention is packaged into collapsible tubes, jars, pot, bottle or single dose packets. The container material or packaging material of the present invention does not affect the quality of the preparation or does not allow diffusion of any kind into or across the material of the container into the preparation

EXAMPLES:
The following Examples are provided solely for illustrative purposes and are not meant to limit the present invention in any way.

Example 1:
Sr. No. Ingredients (mg/g)
1. Luliconazole 10
2. Ketoconazole 20
3. Medium Chain Triglyceride 100
4. Isopropyl Ricinoleate 50
5. Cetostearyl Alcohol 60
6. Stearyl Alcohol 60
7. Polysorbate 80 25
8. Sorbitan Monooleate 25
9. Methyl Paraben 1.5
10. Butylated Hydroxytoluene 0.1
11. Purified Water -

Manufacturing Process:
1. Ketoconazole was dissolved in mixture of medium chain triglycerides, isopropyl ricinoleate and sorbitan monooleate at room temperature.
2. Luliconazole was added to step I, mixed using stirrer and heated at 65-70 °C to form uniform liquid.
3. Butylated hydroxy toluene, methyl paraben, Cetostearyl alcohol, stearyl alcohol were added to step 2, at 65-70 °C to form clear oil phase.
4. Aqueous phase was prepared separately by dissolving polysorbate 80 in water, mixed using stirrer and heated at 65-70 °C.
5. Oil phase of step 3 was added to aqueous phase of step 4, under continuous stirring and cooled to room temperature.
6. Formed cream was filled in tubes and tubes were sealed.

Example 2:
Sr. No. Ingredients (mg/g)
1. Luliconazole 10
2. Ketoconazole 20
3. Medium Chain Triglyceride 77
4. Isopropyl Ricinoleate 10
5. Propylene glycol 250
6. Cetostearyl Alcohol 80
7. Stearyl Alcohol 80
8. Polysorbate 60 25
9. Methyl Paraben 1.5
10. Butylated Hydroxytoluene 0.1
11. Butylated Hydroxyanisole 0.05
12. Purified Water q.s.

Manufacturing Process:
1. Ketoconazole was dissolved in mixture of medium chain triglycerides, isopropyl ricinoleate and propylene glycol at room temperature.
2. Luliconazole & Butylated Hydroxyanisole was added to step I, mixed using stirrer and heated at 65-70 °C to form uniform liquid.
3. Butylated hydroxy toluene, methyl paraben, Cetostearyl alcohol, stearyl alcohol were added to step 2, at 65-70 °C to form clear oil phase.
4. Aqueous phase was prepared separately by dissolving polysorbate 60 in water, mixed using stirrer and heated at 65-70 °C.
5. Oil phase of step 3 was added to aqueous phase of step 4, under continuous stirring and cooled to room temperature.
6. Formed cream was filled in tubes and tubes were sealed.

Example 3:
Sr. No. Ingredients (mg/g)
1. Luliconazole 10
2. Ketoconazole 20
3. Medium Chain Triglyceride 100
4. Isopropyl Myristate 50
5. Propylene glycol 250
6. Cetostearyl Alcohol 80
7. Stearyl Alcohol 80
8. Polyethylene Glycol 400 25
9. Sorbitan Monooleate (Span 80) 25
10. Methyl Paraben 1.5
11. Butylated Hydroxytoluene 0.1
12. Citric Acid 0.01
13. Potassium Sorbate 0.01
14. Purified Water q.s

Manufacturing Process:
1. Ketoconazole was dissolved in mixture of medium chain triglycerides, isopropyl myristate, propylene glycol and sorbitan monooleate (span 80) at room temperature.
2. Luliconazole was added to step I, mixed using stirrer and heated at 65-70 °C to form uniform liquid.
3. Butylated hydroxy toluene, methyl paraben, Cetostearyl alcohol, stearyl alcohol were added to step 2, at 65-70 °C to form clear oil phase.
4. Aqueous phase was prepared separately by dissolving polyethylene glycol in water, mixed using stirrer and heated at 65-70 °C.
5. Oil phase of step 3 was added to aqueous phase of step 4, under continuous stirring and cooled to room temperature.
6. Adjust the pH using citric acid and potassium sorbate to match the range of pH.
7. Formed cream was filled in tubes and tubes were sealed.

Example 4:
Sr. No. Ingredients (mg/g)
1. Luliconazole 10
2. Ketoconazole 20
3. Medium Chain Triglyceride 100
4. Isopropyl Myristate 50
5. Propylene glycol 250
6. Cetostearyl Alcohol 90
7. Stearyl Alcohol 90
8. Polysorbate 80 25
9. Sorbitan Monooleate 25
10. Methyl Paraben 1.5
11. Butylated Hydroxytoluene 0.1
12. Calcium EDTA 1.0
13. Purified Water q.s.

Manufacturing Process:
1. Ketoconazole was dissolved in mixture of medium chain triglycerides, isopropyl myristate, propylene glycol and sorbitan monooleate (span 80) at room temperature.
2. Luliconazole was added to step I, mixed using stirrer and heated at 65-70 °C to form uniform liquid.
3. Butylated hydroxy toluene, methyl paraben, Cetostearyl alcohol, stearyl alcohol were added to step 2, at 65-70 °C to form clear oil phase.
4. Aqueous phase was prepared separately by dissolving polysorbate 80 in water, mixed using stirrer and heated at 65-70 °C and added Calcium EDTA into it.
5. Oil phase of step 3 was added to aqueous phase of step 4, under continuous stirring and cooled to room temperature.
6. Formed cream was filled in tubes and tubes were sealed.

Example 5:
Sr. No. Ingredients (mg/g)
1. Luliconazole 10
2. Ketoconazole 20
3. Medium Chain Triglyceride 100
4. Isopropyl Myristate 50
5. Propylene glycol 250
6. Cetostearyl Alcohol 80
7. Stearyl Alcohol 80
8. Polysorbate 80 25
9. Sorbitan Monooleate 25
10. Sodium Metabisulphite 1.5
11. Butylated Hydroxytoluene 0.1
12. Disodium EDTA 10
13. Citric Acid 0.5
14. Potassium sorbate 0.01
15. Purified Water q.s.

Manufacturing Process:
1. Ketoconazole was dissolved in mixture of medium chain triglycerides, isopropyl myristate, propylene glycol and sorbitan monooleate at room temperature.
2. Luliconazole was added to step I, mixed using stirrer and heated at 65-70 °C to form uniform liquid.
3. Butylated hydroxy toluene, sodium metabisulphite, Cetostearyl alcohol, stearyl alcohol were added to step 2, at 65-70 °C to form clear oil phase.
4. Aqueous phase was prepared separately by dissolving polysorbate 80 in water, mixed using stirrer and heated at 65-70 °C and add disodium EDTA and sodium metabisulphite.
5. Oil phase of step 3 was added to aqueous phase of step 4, under continuous stirring and cooled to room temperature.
6. Adjust the pH using potassium sorbate.
7. Formed cream was filled in tubes and tubes were sealed.

Example 6:
Sr. No. Ingredients (mg/g)
1. Luliconazole 10
2. Ketoconazole 20
3. Medium Chain Triglyceride 100
4. Isopropyl Myristate 50
5. Propylene glycol 250
6. Cetostearyl Alcohol 90
7. Stearyl Alcohol 90
8. Polysorbate 80 25
9. Sorbitan Monooleate 25
10. Methyl Paraben 1.5
11. Butylated Hydroxytoluene 0.1
12. Disodium EDTA 1.0
13. Potassium Sorbate 0.01
14. Purified Water q.s.

Manufacturing Process:
1. Ketoconazole was dissolved in mixture of medium chain triglycerides, isopropyl myristate, propylene glycol and sorbitan monooleate at room temperature.
2. Luliconazole was added to step I, mixed using stirrer and heated at 65-70 °C to form uniform liquid.
3. Butylated hydroxy toluene, methyl paraben, Cetostearyl alcohol, stearyl alcohol were added to step 2, at 65-70 °C to form clear oil phase.
4. Aqueous phase was prepared separately by dissolving polysorbate 80 in water, mixed using stirrer and heated at 65-70 °C and add Disodium EDTA into it.
5. Oil phase of step 3 was added to aqueous phase of step 4, under continuous stirring and cooled to room temperature.
6. Adjust the pH using potassium sorbate.
7. Formed cream was filled in tubes and tubes were sealed.
,CLAIMS:1. A topical pharmaceutical composition, comprising:
i) Luliconazole or salts thereof;
ii) ketoconazole or salts thereof; and
iii) one or more pharmaceutically acceptable excipient.
2. The topical pharmaceutical composition as claimed in claim 1, wherein concentration of the luliconzole or salts thereof ranges from 0.05% to 3% by weight of the composition.
3. The topical pharmaceutical composition as claimed in claim 1 and 4, wherein concentration of the luliconzole or salts thereof is 1% by weight of the composition.
4. The topical pharmaceutical composition as claimed in claim 1, wherein concentration of the ketoconazole or salts thereof ranges from 0.1% to 5% by weight of the composition.
5. The topical pharmaceutical composition as claimed in claim 1 and 4, wherein concentration of the ketoconazole or salts thereof is 2% by weight of the composition.
6. The topical pharmaceutical composition as claimed in claim 1, wherein one or more pharmaceutically acceptable excipient is selected from the group consisting of bases, solubilizing or emulsifying agent, preservative, antioxidant, gelling agent, thickening agent, humectant, adsorbent, permeation enhancer, opacifying agent, chelating agent, acidifying or alkalizing or buffering agent and vehicle.
7. The topical pharmaceutical composition as claimed in claim 1, for use in the treatment of fungal infection(s).