FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULES, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13]
1. Title of the invention: "TOPICAL LULICONAZOLE COMPOSITIONS AND METHODS OF USE THEREOF"
2. Macleods Pharmaceuticals Ltd., an Indian Company, having its Registered Office at 304 - Atlanta Arcade, Opp. Leela Hotel, Marol Church Road, Andheri (East), Mumbai - 400 059, Maharashtra, India.
3. The following specification particularly describes the invention and the manner in which it is to be performed.

FORM 2
THE PATENTS ACT 1970
(39 of 1970)
&
THE PATENTS RULE 2003
COMPLETE SPECIFICATION (Section 10 and rule 13)
TOPICAL LULICONAZOLE COMPOSITIONS AND METHODS OF USE THEREOF
APPLICANT
Macleods Pharmaceuticals Ltd,
304 - Atlanta Arcade, Opp. Leela Hotel, Marol Church Road,
Andheri (East), Mumbai - 400 059, Maharashtra, India
THE FOLLOWING SPECIFICATION DESCRIBES THE INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED

FIELD OF THE INVENTION
The invention relates to topical pharmaceutical composition of luliconazole, and methods of using such composition for the treatment or prevention of fungal skin infections such as tinea pedis, tinea cruris, tinea corporis, and a method of preparing such composition.
The invention specifically relates to a topical gel pharmaceutical composition of luliconazole for the treatment or prevention of fungal skin infections.
BACKGROUND OF THE INVENTION
Fungal infections of the skin known as tinea infections are caused by dermatophytes, which are members of the Trichophyton, Microsporum and Epidermophyton species. These mold-like fungi thrive in warm, moist areas, thriving on the dead tissues of hair, nails, and outer skin layers. Tinea infections include tinea pedis, known as athlete's foot; tinea corporis, known as ringworm; tinea capitis, a fungal infection of the scalp that can cause hair loss; tinea cruris, known as jock itch or tinea of the groin; tinea unguum, which is tinea of the nails; and tinea versicolor, a superficial fungal infection that produces brown, tan, or white spots on the trunk of the body. Tinea infections are contagious and can be passed through direct contact or by contact with clothing, from shower and pool surfaces, and even from pets.
Athlete's foot or tinea pedis is the most common form. It presents with redness, itching, burning, cracking, scaling, swelling and occasionally bleeding. The condition generally includes small vesicles, fissures, scaling, maceration, hyperkeratinization, and eroded areas between the toes and on the plantar surface of the foot, as well as on other skin areas. The nails may show thickening, pitting and subungal debris. Local antifungals include imidazoles, such as miconazole nitrate and clotrimazole, tolnaftate, and terbinafine hydrochloride. The common fungicidal and fungistatic chemical treatments frequently fail to contact the fungi in the horny

layers of the skin, which means athlete's foot slowly clears with local antifungal therapy or systemic antifungals. This requires the infected individual to take treatments for considerable lengths of time, potentially for months. Common treatments for athlete's foot using local antifungals require treatment two or three times a day for at least 7 to 14 days, and for some medications, for up to four weeks. It is common treatment to apply the topical antifungal for two weeks after the skin is healed, to eradicate all remaining fungal spores. Physicians commonly prescribe medications in the form of powders, aerosols, liquids or creams for the treatment of tinea pedis.
Luliconazole is an antimycotic agent in the azole class. Luliconazole 1% cream was approved in Japan in 2005 for the treatment of tinea infections. Luliconazole is currently marketed in United States under the trade name Luzu cream, 1% which contains benzyl alcohol 1% w/w, butylated hydroxytoluene, cetostearyl alcohol, isopropyl myristate, medium-chain triglycerides, methylparaben 0.14% w/w, polysorbate 60, propylene glycol, purified water, and sorbitan monostearate. Luzu 1% cream is indicated for the topical treatment of interdigital tinea pedis, tinea cruris, and tinea corporis caused by the organisms Trichophyton rubrum and Epidermophyton floccosum.
Lulifin 1% lotion in non-aqueous base contains 46% v/v ethanol IP, polyethylene glycol 400, medium-chain triglycerides, ethyl methyl ketone, phosphoric acid and ethanol and is indicated for cutaneous mycosis Tinea: Tinea pedis, tinea corporis and tinea cruris.
Luliconazole is disclosed in International Patent application no. WO9702821. Japanese patent application no. JP2002114680 covers luliconazole composition containing butylated hydroxytoluene, cetostearyl alcohol, isopropyl myristate, medium-chain triglycerides, methylparaben, polysorbate 60, propylene glycol,

purified water, and sorbitan monostearate. U.S. Patent no. US8,962,669 relates to Miconazole compositions comprising a polyhydric alcohol derivative.
U.S. publication no. US2015238606 discloses Miconazole composition containing one or more of carboxylic acid and derivative thereof, ketone, phosphoric acid and derivative thereof, local anaesthetic, antihistamine, and POE-based non-ionic surfactant. International patent application no. WO2007102242 discloses luliconazole is dissolved in propylene carbonate solvent at a concentration of 0.1 to 40% by mass.
International patent application no. WO2007102241 relates to a composition of luliconazole and a-hydroxycarboxylic acid/salt. International patent application no.'s WO2014041708 and WO2014136282 relate to specific crystal habit helps to improve the solubilization of the luliconazole. International patent application no's WO2010117091 and WO2010117089 provide luliconazole composition comprising a higher alcohol and/or a diester of a dibasic acid excluding a diester carbonate, and a polyoxyethylene alkyl ether and/or a polyoxyethylene alkenyl ether. WO2007102242 discloses luliconazole composition comprising one or two or more members selected from among N-methyl-2-pyrrolidone, propylene carbonate, and crotamiton.
WO2015156219 describes pharmaceutical compositions containing a steroid and an antifungal agent. International patent application no. WO2011024620 discloses pharmaceutical compositions of luliconazole with a ketone and a hydroxyalkylbenzene for excellent solubilization and suppressing stereo-isomerization of luliconazole. International patent application no. WO2009031642 relates to an antifungal agent for external application 50-95 % by mass of an alcohol, and 0.1-35 % by mass of water and/or an anionic surfactant.

Like other imidazole-based antifungal agents, Miconazole has low water solubility, so there is a need of using a solvent for its preparation.
There is a considerable need for improvement in the development of topical antifungal compositions suitable for use in the treatment of fungal infections. There still exists a need for improved topical luliconazole compositions with good patient convenience and acceptance.
SUMMARY OF THE INVENTION
The present invention relates to topical pharmaceutical compositions comprising luliconazole, for the treatment or prevention of fungal skin infections such as tinea pedis, tinea cruris, tinea corporis, and a method of preparing such composition.
In particular, the invention relates to topical gel pharmaceutical compositions comprising luliconazole, a solvent system comprising water, one or more water miscible organic solvent, a co-solvent, and polyol ethers, at least one polymeric gelling agent, and one or more pharmaceutically acceptable excipients.
The present invention also relates to a method for the treatment or prevention of fungal infections such as tinea pedis, tinea cruris, tinea corporis by applying a topical gel pharmaceutical composition comprising luliconazole, a solvent system comprising water, one or more water miscible organic solvent, a co-solvent, polyol ethers, at least one polymeric gelling agent, and one or more pharmaceutically acceptable excipients.
The present invention further relates to process of preparing topical gel pharmaceutical compositions of luliconazole.

DETAILED DESCRIPTION OF THE INVENTION
The present invention provides a topical gel pharmaceutical composition for the treatment or prevention of fungal infections containing a therapeutically effective amount of luliconazole.
The terms "treating" and "treatment" are used herein to refer to actions that reduce the severity and/or frequency of symptoms, eliminate symptoms and/or their underlying cause, prevent the occurrence of symptoms and/or their underlying cause, and improve or remediate damage. The present method of "treating" a subject, as the term is used herein, encompasses both prevention and treatment of tinea pedis, tinea cruris, and tinea corporis in an individual.
The terms "prevent" and "prevention" of a fungal infection refers to an action which inhibits or delays onset or exacerbation of one or more symptoms of the disease or disorder.
By "a therapeutically effective amount of luliconazole" is meant a nontoxic but sufficient amount to provide the desired effect, i.e., treatment or prevention of tinea pedis, tinea cruris, and tinea corporis.
The term "topically applied" is used to mean application of a topical drug or pharmacologically active agent to the skin.
Luliconazole, also known as NND-502, is an imidazole antifungal. It has a unique structure as the imidazole moiety is incorporated into the ketene dithioacetate structure. It is an optically related compound of lanoconazole, with a 2,4-dichlorophenyl group on the ketene dithioacetal structure. Similar to lanoconazole, the S-enantiomer is inactive, so luliconazole, being the active R-enantiomer, has more potent antifungal activity than lanoconazole. It has been reported to have strong

in vitro antifungal activity against trichophyton spp., C. albicans, and aspergillus fumigatus.
Luliconazole, chemically known as (2E)-2-[(4R)-4-(2,4-dichlorophenyl)-l,3-dithiolan-2-ylidene]-2-imidazol-l-ylacetonitrile,is represented by the following structural formula (I)

The amount of luliconazole in the topical gel pharmaceutical composition of the present invention ranges from about 0.1 to 15% by weight, more preferably from about 0.5 to 10% by weight, and much more preferably from about 0.5 to 5% by weight.
As used herein, the term "about" when used to refer to weight % in a composition means ±10% of the reported weight %. As used herein, the term "about" when used to refer to measured characteristics of the composition means ±20% of the reported value.
In an embodiment of the invention there is provided topical gel pharmaceutical composition comprising luliconazole, a solvent system comprising water, one or more water miscible organic solvent, a co-solvent, and polyol ethers, at least one gelling agent, and one or more additional pharmaceutically acceptable excipients.

The water miscible organic solvent assists in dissolving the active agent. The solvent may be a single component or a mixture which are miscible with water. Suitable one or more water-miscible solvents include, but are not limited to, alcohols, such as ethanol, isopropanol and the like; polyols. Polyols for use herein can be C2-C30 polyols containing from 2 to about 10 hydroxyl groups. Suitable polyols according to the present invention include, but are not limited to, glycerol, dipropylene glycol, polyethylene glycol, propylene carbonate, propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, propylene glycol monocaprylate and mixtures thereof.
The preferred water miscible organic solvent is propylene glycol. Another preferred organic solvent is polyethylene glycol, such as PEG 400.
In one embodiment, the amount of water-miscible solvent may range from about 30% to about 98% by weight. In another embodiment, the water-miscible solvents are present in an amount of from about 60% to about 98 % by weight. In a preferred embodiment, the water-miscible solvents are present in an amount of from about 80% to about 98% by weight.
The topical gel pharmaceutical composition further comprises a co-solvent. The function of the co-solvent is to help in solubilising (i.e. in conjunction with the organic solvent) luliconazole and/or the polymer in the composition.
One or more co-solvents include, but are not limited to, alcohols such as amyl alcohol, benzyl alcohol, cyclohexanedimethanol, diacetone alcohol, hexyl alcohol, tetrahydrofurfuryl alcohol; carboxylic acids such as acetic acid or multi carboxylic acid derivatives; diols such as 1,2-hexanediol, butylene glycol, diethylene glycol, dipropylene glycol, ethyl hexanediol, ethylene glycol, hexylene glycol, pentylene glycol, tetraethylene glycol, triethylene glycol, tripropylene glycol; and polyols such as, butanetriol, glycerol and 1,2,6-hexanetriol.

In one embodiment, the co-solvent is hexylene glycol. In yet another embodiment, the co-solvent is a mixture of at least two co-solvents. In a most preferred embodiment, the co-solvent is benzyl alcohol.
In one embodiment, the co-solvent is present in the composition in an amount of from about 1% to about 15% by weight. In another embodiment, the co-solvent is present in an amount of from about 1% to about 10% by weight. In yet another embodiment, the co-solvent is present in an amount of from about 1% to about 5% by weight. In a most preferred embodiment, the topical gel pharmaceutical composition of present invention comprises at least 2% of a co-solvent.
The polyol ethers for use in present invention include C2-C30 polyol ethers containing from 2 to about 10 hydroxyl groups. Representative of the polyol ethers are glycol ethers which include, by way of example and without limitation, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, ethylene glycol monopropyl ether, ethylene glycol monophenyl ether, ethylene glycol monohexyl ether, diethylene glycol monoethyl ether, diethylene glycol monomethyl ether, triethylene glycol monomethyl ether, triethylene glycol monoethyl ether, ethylene glycol monopropyl ether, ethylene glycol monobutyl ether, diethylene glycol monobutyl ether, triethylene glycol monobutyl ether, ethylene glycol monohexyl ether, diethyl glycol monohexyl ether, ethylene glycol phenyl ether, polyethylene glycol, polyethylene glycol dodecyl ether, diethylene glycol monoethyl ether, polyethylene glycol-8-glyceryl caprylate and the like and mixtures thereof.
Diethylene glycol monoethyl ether, commercially available as Transcutol®, is a preferred polyol ether.
The polyol ether is present in the composition in an amount from about 0.1% to about 15% by weight. In one embodiment the polyol ether is present in the

composition in an amount from about 1% to about 10% by weight, preferably from about 1% to about 5% by weight.
In one embodiment, the solvent system is a mixture of water, a polyol, an alcohol and a polyol ether.
In one embodiment, the solvent system is a mixture of a polyol, an alcohol and polyol ether. In a preferred embodiment the solvent system is a mixture of propylene glycol, polyethylene glycol, benzyl alcohol and diethylene glycol monoethyl ether.
In a preferred embodiment, the present invention provides a topical gel pharmaceutical composition comprising propylene glycol, polyethylene glycol, benzyl alcohol and diethylene glycol monoethyl ether as a solvent system, in amounts such that the composition forms a clear, aqueous dispersion.
In one or more embodiment solvent system comprises a mixture of from about from about 30% to about 50%) by weight of propylene glycol, from about 30% to about 50% by weight of polyethylene glycol, from about from about 1% to about 5% by weight of benzyl alcohol and from about from about 1% to about 5% by weight of diethylene glycol monoethyl ether. In another embodiment solvent system further comprises up to about 25% by weight of water.
In one or more embodiment solvent system comprises a mixture of from about from about 30%) to about 50%) by weight of propylene glycol, from about 30% to about 50% by weight of polyethylene glycol, from about from about 1% to about 5% by weight of benzyl alcohol, from about 1% to about 5% by weight of diethylene glycol monoethyl ether and up to about 25%> by weight of water.
It has now been surprisingly found that a mixture of propylene glycol, polyethylene glycol, benzyl alcohol and diethylene glycol monoethyl ether in specific proportions

are effective to solubilize drug, and thus are found suitable to be utilized in the preparation of topical gel pharmaceutical compositions of the invention.
The topical gel pharmaceutical composition of present invention further comprises a polymeric gelling agent.
The polymeric gelling agents include, but are not limited to, a carbomer, acrylate copolymers, agar, alginate, arabinoxylan, carrageenan, a cellulose-based thickener like hydroxyethylcellulose or hydroxypropylcellulose, hydroxypropyl methylcellulose, carboxymethylcellulose, curdlan, gelatin, gellan, P-glucan, tragacanth gum, guar gum, gum arabic, locust bean gum, pectin, starch, silica, xanthan gum, salts thereof, or a combination or mixture thereof.
The polymeric gelling agents that have been found to be particularly useful in the composition of the present invention are lightly cross-linked polyacrylic acid polymers which are available under the tradename CARBOPOL®. They are generically referred to as carbomers. The CARBOPOL polymers are hydrophilic polymers based on a polyacrylic acid structure. For use in the present invention the lightly cross-linked polymers include CARBOPOL 980, 910, 941,971, and 981 and CARBOPOL ETD 2050.
The polymeric gelling agents are present in the composition in an amount from about 0.1% to about 5% by weight. In one embodiment the polymeric gelling agents is present in the composition in an amount from about 0.1% to about 3% by weight, preferably from about 0.1% to about 1.5% by weight.
In an embodiment, the topical gel pharmaceutical composition further comprises one or more dermatologically acceptable excipients such as humectants, preservatives, fragrances, colorants, penetration enhancers, or a combination or mixture thereof.

The humectants include, but are not limited to, glycerol, sorbitol, maltitol, polydextrose, triacetin, propylene glycol, polyethylene glycol (PEG) esters including PEG-20 stearate, PEG-40 stearate, PEG-150 stearate, PEG-150 distearate and PEG-100 stearate, alkoxylated alcohols including laureth-12, ceteareth-20, laureth-23, glycereth-7, glycereth-12, glycereth-26, PEG-4, PEG-6, PEG-8, PEG-12, PEG-32, PEG-75, PEG-150, or a combination or mixture thereof. In an embodiment, the humectant is glycerol. In one embodiment, the topical gel pharmaceutical composition comprises about 0.1% to about 10% by weight of a humectant.
The Preservatives can be selected from, but are not limited to, benzyl alcohol, diazolidinyl urea, methyl paraben, ethyl paraben, propyl paraben, butyl paraben, phenoxyethanol, sorbic acid, benzoic acid, salts thereof, or a combination or mixture thereof. Suitably, the topical gel pharmaceutical composition comprises a preservative in an amount from about 0.01% to about 2% by weight.
In one embodiment, the invention provides a topical gel pharmaceutical composition comprising: Miconazole, a solvent system comprising a mixture of water, propylene glycol, benzyl alcohol, diethylene glycol monoethyl ether, and polyethylene glycol, carbopol as a polymeric gelling agent, and one or more additional pharmaceutically acceptable excipients.
In yet another embodiment, the present invention provides a topical gel pharmaceutical composition that comprises from about 0.5 to 5% by weight of luliconazole, from about 80% to about 95% by weight of polyol, from about from about 1% to about 5% by weight of benzyl alcohol, from about 1% to about 5% by weight of diethylene glycol monoethyl ether, about 0.1% to about 3% by weight of carbopol, and one or more additional pharmaceutically acceptable excipients.
In a most preferred embodiment, the present invention provides a topical gel pharmaceutical composition consisting of about 1% by weight of luliconazole, about

46% by weight of propylene glycol, at least 2% by weight of benzyl alcohol, about 5% by weight of diethylene glycol monoethyl ether, about 46% by weight of polyethylene glycol, about 1.5 % by weight of carbopol, and one or more additional pharmaceutically acceptable excipients.
In another embodiment of this invention, there is also provided a process for preparing the topical gel pharmaceutical composition, which comprises the steps of preparing a drug phase, and preparing a gel base and mixing both phases to form a homogeneous and transparent gel.
In one embodiment the process for preparing the topical gel pharmaceutical composition, comprises the steps of preparing a drug dispersion by dissolving the drug in a solvent system comprising a mixtures of solvents, followed by addition of polymeric gelling agent and further heating the resultant mixture to form a homogeneous and transparent gel.
The composition of this invention may be, for example, filled and packaged into a container such as glass jars and aluminum or laminate tubes, a plastic or glass tube or a jar or a bottle, an airless pump and plastic squeeze bottle, appropriate for packaging topical formulations.
The product may further contain additional packaging such as a plastic or cardboard box for storing such container. In one embodiment, the product comprises a composition of the invention and contains instructions directing the user to apply the composition to the skin.
The labeling instructions can come in the form of a pamphlet, a label applied to or associated with the packaging which indicates directions for use in the treatment of fungal infections.

In one embodiment, a method for the treatment or prevention of fungal infections comprising the topical administration of a composition is provided herein.
In another embodiment, there is provided a method for treating or preventing fungal skin infections such as tinea pedis, tinea cruris, tinea corporis, tinea manuum, tinea unguium, tinea versicolor, candidiasis, onychomycosis, aspergillosis, or combinations thereof comprising applying preceding topical gel pharmaceutical compositions.
In one embodiment, a kit comprising a luliconazole composition is also provided, and may further comprise instructions for use, such as in the treatment of fungal skin infections i.e, tinea pedis, tinea cruris, tinea corporis, tinea manuum, tinea unguium, tinea versicolor, candidiasis, onychomycosis, aspergillosis, or combinations thereof.
The topical gel pharmaceutical composition can be applied once daily or more than once, or as needed for the duration of the treatment period until the desired effect is obtained. In one or more embodiment the user is directed to apply the medicament to the affected area once daily for a period of one to four weeks. In another embodiment composition may be applied once daily for a period of one week or two week.
Different tests are available for the determination of fungal resistance. In one embodiment, the standardized disc test according to Kirby-Bauer is used for this purpose. The disc test according to Kirby-Bauer is based on the impregnation of filter discs and measuring of the corona of inhibition after applying the filters to inoculated agar plates.
In one embodiment, the antifungal activity of topical gel pharmaceutical composition of present invention was measured according to Kirby-Bauer test against Candida albicans species. The experiments showed that luliconazole topical gel composition inhibited the zone of growth of Candida albicans cells.

EXAMPLES
The invention is further illustrated in the following examples which are meant to be exemplary and not limiting.
EXAMPLE 1

Table 1: Manufacturing formula
Ingredients Weight Percent
Luliconazole 1.00
Carbomers ( Carbopol® 980NF) 1.20
Polyethylene glycol 400 (Macrogols 400) 45.35
10
Propylene Glycol 45.45
Diethylene glycol monoethyl ether (Transcutol® P) 5.00
Benzyl alcohol 2.00
Manufacturing process:
1. Preparation of drug phase
1.1. Weighed quantities of propylene glycol, benzyl alcohol and diethylene glycol monoethyl ether were added to a vessel followed by adding luliconazole slowly in small portions under continuous stirring until a clear solution was obtained.
2. Preparation of gel base
2.1. Carbopol 980 was added to a vessel containing polyethylene glycol 400 under continuous stirring to form a uniform dispersion.

2.2. Dispersion formed in step 2.1 was heated at a temp, of about 50° C under continuous stirring to obtain a clear, uniform gel. The resultant gel base was allowed to cool at room temp.
3. Preparation of Gel
3.1 The drug phase formed in step 1.1 was added to the gel base formed in step 2.2 under continuous stirring and the resultant gel was kept under vacuum for about 1 -2 hrs with intermittent stirring until a transparent gel, free of entrapped air, was formed
EXAMPLE 2

Table 2: Manufacturing formula
Ingredients Weight Percent
Luliconazole 1.00
Propylene Glycol 35.00
Diethylene glycol monoethyl ether (Transcutol P®) 5.00
Benzyl Alcohol 2.00
Polyethylen Glycol 400 (Macrogols 400) 35.00
Carbopol® 980 NF 1.20
Purified Water 21.10
Manufacturing process:
1. Preparation of drug phase
1.1. Weighed quantities of propylene glycol, benzyl alcohol, diethylene glycol monoethyl ether were added to a vessel followed by adding luliconazole slowly in small portions under continuous stirring until a clear solution was obtained.

2. Preparation of gel base
2.1. Carbopol 980 NF was dispersed in polyethylene glycol 400 under continuous stirring till a lump free dispersion is obtained.
2.2 Purified water was added to step 2.1 under continuous stirring. The resultant dispersion was kept aside under intermittent stirring to allow complete swelling of Carbopol.
2.3 The dispersion formed in step 2.2 was heated upto 50°C under stirring to get lump free gel base.
3. Preparation of gel
3.1 The gel base from step 2.3 was allowed to cool to about 35°C to 40°C. Drug phase from step 1.1 was added to this gel base and stirred.
3.2 The resultant gel was kept under vacuum with intermittent stirring till a uniform gel free of entrapped air is obtained.
EXAMPLE 3: Skin Permeation Study with luliconazole gel formulation
In vitro release testing (IVRT) study was performed to compare the permeation of topical gel pharmaceutical composition of luliconazole with currently marketed luliconazole topical cream composition. In vitro permeation of luliconazole topical gel compositions through nylon membrane having a pore diameter of 0.45 µ was performed using Franz diffusion cell using methanol and water as receptor medium. In vitro permeation data obtained for luliconazole cream 1% was compared with data derived from exemplary compositions according to the present invention (e.g., luliconazole gel 1%) as shown in table 3.
Table 3: Comparison of skin permeability of gel formulation versus cream formulation:

Time (Hr) Luliconazole Gel 1%
w/w (% Release) Luliconazole Cream
(Lulifin) 1% w/w
(% Release)
1 41.2 15.5
2 64.3 25.6
3 69.8 34.0
4 70.6 40.7
5 70.9 45.6
As it is apparent from the data shown in above table, the rate and extent of permeation achieved with luliconazole 1% gel of the present invention was greater than that achieved with luliconazole cream 1% (Lulifin).

I/We claim:
1. A topical gel pharmaceutical composition, for the treatment of fungal skin
infections, comprising:
(a) luliconazole;
(b) a solvent system comprising a mixture of water, one or more water miscible organic solvent, and a co-solvent;
(c) at least one polymeric gelling agent, and one or more additional pharmaceutically acceptable excipients.
2. The topical gel pharmaceutical composition according to claim 1, wherein
luliconazole is present in an amount from about 0.1% to about 5%, by weight of the
composition.
3. The topical gel pharmaceutical composition according to claim 1, wherein water miscible organic solvent is selected from glycerol, dipropylene glycol, polyethylene glycol, propylene carbonate, propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, propylene glycol monocaprylate, thylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, ethylene glycol monopropyl ether, ethylene glycol monophenyl ether, ethylene glycol monohexyl ether, diethylene glycol monoethyl ether, diethylene glycol monomethyl ether, triethylene glycol monomethyl ether, triethylene glycol monoethyl ether, ethylene glycol monopropyl ether, ethylene glycol monobutyl ether, diethylene glycol monobutyl ether, triethylene glycol monobutyl ether, ethylene glycol monohexyl ether, diethyl glycol monohexyl ether, ethylene glycol phenyl ether, polyethylene glycol dodecyl ether, polyethylene glycol-8-glyceryl caprylate and mixtures thereof.
4. The topical gel pharmaceutical composition according to claim 1, wherein a co-solvent is selected from amyl alcohol, benzyl alcohol, cyclohexanedimethanol,

diacetone alcohol, hexyl alcohol, tetrahydrofurfuryl alcohol; acetic acid or multi carboxylic acid derivatives; 1,2-hexanediol, butylene glycol, diethylene glycol, dipropylene glycol, ethyl hexanediol, ethylene glycol, hexylene glycol, pentylene glycol, tetraethylene glycol, triethylene glycol, tripropylene glycol;, butanetriol, glycerol and 1,2,6-hexanetriol and mixtures thereof.
5. The topical gel pharmaceutical composition according to claim 1, wherein solvent system comprises propylene glycol, polyethylene glycol, diethylene glycol monoethyl ether and benzyl alcohol.
6. The topical gel pharmaceutical composition according to claim 1, wherein solvent system is present in the composition in an amount from about 60% to about 98 % by weight of the composition.
7. The topical gel pharmaceutical composition according to claim 1, wherein the at least one polymeric gelling agent is selected from carbomer, acrylate copolymers, agar, alginate, arabinoxylan, carrageenan, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, carboxymethylcellulose, curdlan, gelatin, gellan, P-glucan, tragacanth gum, guar gum, gum arabic, locust bean gum, pectin, starch, silica, xanthan gum, salts thereof, or a mixture thereof.
8. A topical gel pharmaceutical composition, comprising;

(a) about 1% by weight of luliconazole;
(b) a solvent system comprising about 46% by weight of propylene glycol, about 46% by weight of polyethylene glycol, about 5% by weight of, diethylene glycol monoethyl ether, about 2% by weight of benzyl alcohol;
(c) about 1.5% by weight of a polymeric gelling agent comprising carbopol; and one or more additional pharmaceutically acceptable excipients.

9. A method for the treatment or prevention of fungal infections comprising the step
of administering, to a subject, the pharmaceutical composition according to claim 8,
in an amount sufficient for treating or preventing fungal infection.
10. The method for the treatment or prevention of fungal infections according to
claim 9, wherein the method comprises administering the composition for the
treatment of tinea pedis, tinea cruris, and tinea corporis.