FORM 2
THE PATENT ACT, 1970
(39 Of 1970)
AND
THE PATENTS RULES, 2003
COMPLETE SPECIFICATION
(See section 10; rule13)
1. TITLE OF THE INVENTION:
LULICONAZOLE TOPICAL COMPOSITIONS
2. APPLICANT(S)
(a) Name: GLENMARK PHARMACEUTICALS LIMITED
(b) Nationality: INDIAN
(c) Address: Glenmark Pharmaceuticals Limited, B/2 Mahalaxmi Chambers
22, Bhulabhai Desai Road,Mumbai – 400 026.
3. PREAMBLE TO THE DESCRIPTION
COMPLETE
The following specification describes The following specification particularly
the invention describes the invention and the manner
in which it is to be performed.

LULICONAZOLE STABLE TOPICAL COMPOSITIONS
PRIORITY DOCUMENT
This patent application claims priority to Indian Provisional Patent Application number 201621017933 (filed on May 25, 2016), the contents of which are incorporated by reference herein.
FIELD OF THE INVENTION
The present invention relates to stable topical compositions comprising Luliconazole. Further the present invention also relates to stable topical compositions comprising combination of luliconazole with a corticosteroid such as betamethasone or clobetasol. The compositions are free of an aliphatic alcohol and a ketone.
BACKGROUND OF THE INVENTION
Luliconazole is an imidazole antifungal that has been approved first in Japan for topical treatments of fungal infections. Luliconazole is represented by a structural formula (I)

Formula (I)
Lulifine 1% Cream 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. Lulifine 1% Cream is indicated for the treatment of cutaneous mycosis Tinea: Tinea pedis, tinea corporis and tinea cruris; Candidiasis: Intertrigo and interdigital erosion, Tinea versicolor. 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 publication no. WO9702821. Japanese patent application publication 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. International patent application publication no.WO2011155640 relates to luliconazole compositions comprising a polyhydric alcohol derivative. International patent application publication no. WO2014042043 discloses luliconazole 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 publication no. WO2007102242 discloses Luliconazole is dissolved in propylene carbonate solvent at a concentration of 0.1 to 40% by mass. International patent application publication no. WO2007102241 relates to a composition of luliconazole and α-hydroxycarboxylic acid/salt. International patent application publication no.s WO2014041708 and WO2014136282 relate to Specific crystal habit helps to improve the solubilization of the luliconazole. International patent application publication no.s WO2010117091 and WO2010117089 provide luliconazole composition comprising a higher alc. 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 publication 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 publication

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. Excipient like alcohol may cause hydrolysis or the like to affect the stability of an active. The compound may not be sufficiently dissolved and may be time-dependently precipitated when an alcohol amount is small, whereas an excess alcohol amount may impair the pharmaceutical acceptability.
The present invention discloses stable topical compositions comprising luliconazole wherein the compositions are free of an aliphatic alcohol and a ketone. Further the stable topical compositions of the present invention are free of an aliphatic alcohol and a ketone.
SUMMARY OF THE INVENTION
The present invention relates to stable topical compositions comprising Luliconazole. Further the present invention also relates to stable topical compositions comprising combination of luliconazole with a corticosteroid such as betamethasone or clobetasol.
In one embodiment, the present invention relates to stable topical composition comprising luliconazole wherein; the compositions are free of an aliphatic alcohol and a ketone.
In one embodiment, the present invention relates to stable topical composition comprising luliconazole wherein; the compositions are free of an aliphatic alcohol and a ketone; and wherein the stable topical composition further comprises one or more pharmaceutical excipients selected from a group consisting of a medium chain triglyceride, a polyhydric alcohol, and an ester of a fatty acid.
In one aspect of this embodiment, the medium chain triglyceride is selected from medium-chain triglycerides of the olive oil, coconut oil, or palm kernel oil. Preferably the medium chain alcohol is medium-chain triglycerides of coconut oil.
In another aspect of this embodiment, the polyhydric alcohol is selected from ethylene glycol, propylene glycol, hexylene glycol, glycerol, erythritol or sorbitol. Preferably the polyhydric alcohol is propylene glycol or hexylene glycol.

In yet another aspect of this embodiment, the ester of fatty acids is selected from higher fatty acids such as oleic acid, isostearic acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, and undecylenic acid. Preferably ester of fatty acid is isopropyl myristate.
In a preferred aspect of this embodiment, the stable topical composition comprises caprylic /capric triglyceride, propylene glycol or hexylene glycol and isopropyl myristate.
In one embodiment, the stable topical composition comprising luliconazole of the present invention further comprises one or more additional pharmaceutical excipients selected from a group consisting a chelating agent and a preservatives.
In one aspect of this embodiment, the chelating agents selected from a group consisting of ethylene diamine tetra-acetic acid (EDTA), disodium edetate and or any combination thereof.
In another aspect of this embodiment, the preservatives selected from a group consisting of phenoxyethanol, parabens such as methyl paraben and propyl paraben, propylene glycols, sorbates, benzyl alcohol, butylated hydroxyl toluene, urea derivatives such as diazolindinyl urea, and the like or any combinations thereof.
In one embodiment, the stable topical composition comprises one or more of 0.5% -2% of luliconazole, 1%-20% of caprylic /capric triglyceride, 1%-25% of propylene glycol or hexylene glycol, 1%-10% of isopropyl myristate, 0.05%-2% of a preservative and 0.01%-1% of a chelating agent by weight of the composition.
In one embodiment, the stable topical composition comprises one or more of 0.5% -2% of luliconazole, 30%-80% of caprylic /capric triglyceride, 1%-25% of propylene glycol or hexylene glycol, 15%-50% of isopropyl myristate, 0.05%-2% of a preservative and 0.01%-1% of a chelating agent by weight of the composition.
In one embodiment, the stable topical composition of the present invention may comprise from about 30%-95% by weight of one or more vehicles selected

from diethanolamine lauryl slulphate, propylene glycol, purified water.
The present invention also provides stable topical composition comprising luliconazole in combination with a corticosteroid. Steroids reduce inflammation of the skin, increases tissue infiltration of the antifungal agent.
In one embodiment, the present invention relates to stable topical composition comprising luliconazole in combination with a corticosteroid wherein; the corticosteroid is selected from a group consisting of hydrocortisone, prednisolone, dexamethasone, clobetasol, betamethasone, beclomethasone, mometasone or salts thereof.
In one aspect of this embodiment, the corticosteroid is beclomethasone dipropionate.
In another aspect of this embodiment, the corticosteroid is clobetasol propionate.
In In one embodiment, the present invention relates to a stable topical composition luliconazole and a corticosteroid wherein; the compositions are free of an aliphatic alcohol and a ketone.
In one embodiment, the present invention relates to stable topical composition comprising luliconazole and a corticosteroid wherein; the compositions are free of an aliphatic alcohol and a ketone; and wherein the stable topical composition further comprises one or more pharmaceutical excipients selected from a group consisting of a medium chain triglyceride, a polyhydric alcohol, and an ester of a fatty acid.
In one aspect of this embodiment, the medium chain triglyceride is selected from medium-chain triglycerides of the olive oil, coconut oil, or palm kernel oil. Preferably the medium chain triglyceride is medium-chain triglycerides of coconut oil.
In another aspect of this embodiment, the polyhydric alcohol is selected from ethylene glycol, propylene glycol, hexylene glycol, glycerol, erythritol or sorbitol. Preferably the polyhydric alcohol is propylene glycol or hexylene glycol.
In yet another aspect of this embodiment, the ester of fatty acids is selected from higher fatty acids such as oleic acid, isostearic acid, lauric acid, myristic

acid, palmitic acid, stearic acid, behenic acid, and undecylenic acid. Preferably ester of fatty acid is isopropyl myristate.
In a preferred aspect of this embodiment, the stable topical composition comprises caprylic /capric triglyceride, propylene glycol or hexylene and isopropyl myristate.
In one embodiment, the stable topical composition comprising luliconazole and a corticosteroid of the present invention further comprises one or more additional pharmaceutical excipients selected from a group consisting a chelating agent and a preservatives.
In one aspect of this embodiment, the chelating agents selected from a group consisting of ethylene diamine tetra-acetic acid (EDTA), disodium edetate and or any combination thereof.
In another aspect of this embodiment, the preservatives selected from a group consisting of phenoxyethanol, parabens such as methyl paraben and propyl paraben, propylene glycols, sorbates, benzyl alcohol, butylated hydroxyl toluene, urea derivatives such as diazolindinyl urea, and the like or any combinations thereof.
In one embodiment, the stable topical composition comprises one or more of 0.5% -2% of luliconazole, 0.01%-1% of a corticosteroid, 1%-20% of caprylic /capric triglyceride, 1%-25% of propylene glycol or hexylene glycol, 1%-10% of isopropyl myristate, 0.05%-2% of a preservative and 0.01%-1% of a chelating agent by weight of the composition.
In one embodiment, the stable topical composition comprises one or more of 0.5% -2% of luliconazole, 0.01%-1% of a corticosteroid, 30%-80% of caprylic /capric triglyceride, 1%-25% of propylene glycol or hexylene glycol, 15%-50% of isopropyl myristate, 0.05%-2% of a preservative and 0.01%-1% of a chelating agent by weight of the composition.
In one embodiment, the stable topical composition of the present invention is in the form of any of the dosage form such as gels, creams, ointments, lotions, shampoo, powders, suspensions and solutions.
In one embodiment, the stable topical composition of the present invention

is for use in treating fungal infections.
In one embodiment, the present invention relates to method of treating fungal infections with stable topical composition of the invention.
In one embodiment, the present invention relates to method of treating fungal infections using stable topical composition of the invention.
DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to stable topical compositions comprising luliconazole. Further the present invention also relates to stable topical compositions comprising combination of luliconazole with a corticosteroid such as betamethasone or clobetasol.
The term “active” as used herein means luliconazole or a corticosteroid or its salts, or some additional actives as described herein or combination thereof.
The term "stable topical composition" is used to refer to a pharmaceutical composition for application to body surfaces such as the skin or mucous membranes to treat ailments. The composition may be in any of a range of dosage forms including but not limited to creams, foams, shampoos, powders, gels, lotions, patches, ointments, suspensions and solutions. The stable topical composition may be epicutaneous, meaning that it is applied directly to the skin or mucosa. The effect of the stable topical composition in the pharmacodynamics sense, may be local and primarily address condition of the skin including either or both of the epidermis and underlying dermal layers and/or tissue such as muscles, bones, ligaments and internal organs covered by the skin rather than systemic, or be systemic or provide both local and systemic effects. Stable topical compositions can be used for both stable topical and transdermal administration of substances.
The term “luliconazole” as used herein, unless mentioned otherwise mentioned, means 2(2E)-2-[(4R)-4-(2, 4-dichlorophenyl)-1, 3-dithiolan-2-ylidene]-2-imidazol-1-ylacetonitrile, hydrates, solvates or salts thereof.
The term “corticosteroid” as used herein, includes hydrocortisone, prednisolone, dexamethasone, clobetasol, betamethasone, beclomethasone,

mometasone or salts thereof.
By “salt” or “pharmaceutically acceptable salt”, it means those salts and esters 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, and allergic response, commensurate with a reasonable benefit to risk ratio, and effective for their intended use. Representative salts include the hydrochloride, furoate, hydrobromide, sulphate, bisulphate, acetate, oxalate, valerate, propionate, dipropionate, oleate, palmitate, stearate, laurate, borate, benzoate, lactate, phosphate, tosylate, mesylate, citrate, maleate, fumarate, succinate, tartrate, ascorbate, glucoheptonate, lactobionate, and lauryl sulphate salts.
The term “% by weight” unless otherwise mentioned, means percentage w/w with respect to finished dosage form or stable topical composition.
In one embodiment, the present invention relates to stable topical composition comprising luliconazole wherein; the compositions are free of an aliphatic alcohol and a ketone.
In one embodiment, the present invention relates to stable topical composition comprising luliconazole wherein; the compositions are free of an aliphatic alcohol and a ketone; and wherein the stable topical composition further comprises one or more pharmaceutical excipients selected from a group consisting of a medium chain triglyceride, a polyhydric alcohol, and an ester of a fatty acid.
In one aspect of this embodiment, the medium chain triglyceride is selected from medium-chain triglycerides of the olive oil, coconut oil, or palm kernel oil. Preferably the medium chain alcohol is medium-chain triglycerides of coconut oil.
In another aspect of this embodiment, the polyhydric alcohol is selected from ethylene glycol, propylene glycol, hexylene glycol, glycerol, erythritol or sorbitol. Preferably the polyhydric alcohol is propylene glycol or hexylene glycol.
In yet another aspect of this embodiment, the ester of fatty acids is selected from higher fatty acids such as oleic acid, isostearic acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, and undecylenic acid. Preferably

ester of fatty acid is isopropyl myristate.
In a preferred aspect of this embodiment, the stable topical composition comprises caprylic /capric triglyceride, propylene glycol or hexylene glycol and isopropyl myristate.
In one embodiment, the stable topical composition comprising luliconazole of the present invention further comprises one or more additional pharmaceutical excipients selected from a group consisting a chelating agent and a preservatives.
In one aspect of this embodiment, the chelating agents selected from a group consisting of ethylene diamine tetra-acetic acid (EDTA), disodium edetate and or any combination thereof.
In another aspect of this embodiment, the preservatives selected from a group consisting of phenoxyethanol, parabens such as methyl paraben and propyl paraben, propylene glycols, sorbates, benzyl alcohol, butylated hydroxyl toluene, urea derivatives such as diazolindinyl urea, and the like or any combinations thereof.
In one embodiment, the stable topical composition comprises one or more of 0.5% -2% of luliconazole, 1%-20% of caprylic /capric triglyceride, 1%-25% of propylene glycol or hexylene glycol, 1%-10% of isopropyl myristate, 0.05%-2% of a preservative and 0.01%-1% of a chelating agent by weight of the composition.
In one embodiment, the stable topical composition comprises one or more of 0.5% -2% of luliconazole, 30%-80% of caprylic /capric triglyceride, 1%-25% of propylene glycol or hexylene glycol, 15%-50% of isopropyl myristate, 0.05%-2% of a preservative and 0.01%-1% of a chelating agent by weight of the composition.
In one embodiment, the stable topical composition of the present invention may comprise from about 30%-95% by weight of one or more vehicles selected from diethanolamine lauryl sulphate, propylene glycol, purified water.
The present invention also provides stable topical composition comprising luliconazole in combination with a corticosteroid. Steroids reduce inflammation of

the skin, increases tissue infiltration of the antifungal agent.
In one embodiment, the present invention relates to stable topical composition comprising luliconazole in combination with a corticosteroid wherein; the corticosteroid is selected from a group consisting of hydrocortisone, prednisolone, dexamethasone, clobetasone, clobetasol, betamethasone, beclomethasone, mometasone or salts thereof.
In one aspect of this embodiment, the corticosteroid is beclomethasone dipropionate.
In another aspect of this embodiment, the corticosteroid is clobetasol propionate.
In In one embodiment, the present invention relates to a stable topical composition luliconazole and a corticosteroid wherein; the compositions are free of an aliphatic alcohol and a ketone.
In one embodiment, the present invention relates to stable topical composition comprising luliconazole and a corticosteroid wherein; the compositions are free of an aliphatic alcohol and a ketone; and wherein the stable topical composition further comprises one or more pharmaceutical excipients selected from a group consisting of a medium chain triglyceride, a polyhydric alcohol, and an ester of a fatty acid.
In one aspect of this embodiment, the medium chain triglyceride is selected from medium-chain triglycerides of the olive oil, coconut oil, or palm kernel oil. Preferably the medium chain triglyceride is medium-chain triglycerides of coconut oil.
In another aspect of this embodiment, the polyhydric alcohol is selected from ethylene glycol, propylene glycol, hexylene glycol, glycerol, erythritol or sorbitol. Preferably the polyhydric alcohol is propylene glycol or hexylene glycol.
In yet another aspect of this embodiment, the ester of fatty acids is selected from higher fatty acids such as oleic acid, isostearic acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, and undecylenic acid. Preferably ester of fatty acid is isopropyl myristate.
In a preferred aspect of this embodiment, the stable topical composition

comprises caprylic /capric triglyceride, propylene glycol or hexylene glycol and isopropyl myristate.
In one embodiment, the stable topical composition comprising luliconazole and a corticosteroid of the present invention further comprises one or more additional pharmaceutical excipients selected from a group consisting a chelating agent and a preservatives.
In one aspect of this embodiment, the chelating agents selected from a group consisting of ethylene diamine tetra-acetic acid (EDTA), disodium edetate and or any combination thereof.
In another aspect of this embodiment, the preservatives selected from a group consisting of phenoxyethanol, parabens such as methyl paraben and propyl paraben, propylene glycols, sorbates, benzyl alcohol, butylated hydroxyl toluene, urea derivatives such as diazolindinyl urea, and the like or any combinations thereof.
In one embodiment, the stable topical composition comprises one or more of 0.5% -2% of luliconazole, 0.01%-1% of a corticosteroid, 1%-20% of caprylic /capric triglyceride, 1%-25% of propylene glycol or hexylene glycol, 1%-10% of isopropyl myristate, 0.05%-2% of a preservative and 0.01%-1% of a chelating agent by weight of the composition.
In one embodiment, the stable topical composition comprises one or more of 0.5% -2% of luliconazole, 0.01%-1% of a corticosteroid, 30%-80% of caprylic /capric triglyceride, 1%-25% of propylene glycol or hexylene glycol, 15%-50% of isopropyl myristate, 0.05%-2% of a preservative and 0.01%-1% of a chelating agent by weight of the composition.
The stable topical composition of the present invention may further comprise some additional active agents selected from a group consisting of bacitracin, erythromycin, neomycin, tetracycline, chlortetracycline, benzethonium chloride, phenol, finasteride, ketoconazole, salicylic acid, zinc pyrithione, coal tar, benzoyl peroxide, selenium sulfide, hydrocortisone, sulfur, menthol, pramoxine hydrochloride, tricetylmonium chloride, polyquaternium 10, panthenol, panthenol triacetate, vitamin A and derivatives thereof, vitamin B and derivatives thereof,

vitamin C and derivatives thereof, vitamin D and derivatives thereof, vitamin E and derivatives thereof, vitamin K and derivatives thereof, keratin, lysine, arginine, hydrolyzed wheat proteins, hydrolyzed silk proteins, octyl methoxycinnamate, oxybenzone, minoxidil, titanium dioxide, zinc dioxide, retinol, erthromycin, tretinoin, clotrimazole, itraconazole, miconazole, sulconazole, butoconazole, fluconazole, miconazole and mixtures thereof.
The stable topical composition of the present invention may further comprise suitable additional excipient include but not limited to acrylamide/ sodium acryloyldimethyl taurate, isohexadecane, polyoxyethylene sorbitan monooleate, sorbitan monostearate, N-methyl-2-pyrrolidone, glycerin, glyceryl monooleate, glyceryl monostearate, polyglyceryl stearate, polyglyceryl myristate, hydrogenated lecithin, diethanolamine cetyl phosphate, diisopropyl adipate, lanolin, lanolin alcohol, hydrogenated lanolin, liquid paraffins, diethanolamine, diisopropanolamine, triethanolamine, acetic acid, citric acid, fumaric acid, lactic acid, malic acid, tartaric acid, Cetomacrogol E wax, polyoxyethyl cetyl ether (Brij 58), butylated hydroxy toluene, Chlorocresol, purified water, citric acid monohydrate, sodium citrate, Aniseed N flavour, sodium saccharin, glycerol mono ricinoleate, Bouquet I.D. 14013m, ethylene glycol stearates, gum acacia, 2-(trichloromethylthio)-3a,4,7,7a-tetrahydroisoindole-1,3-dione (Vancide 89), perfume powder 7238, colloidal silicon dioxide, starch (maize starch), allantoin, and mixtures thereof.
In one embodiment, the stable topical composition of the present invention is in the form of any of the dosage form such as gels, creams, ointments, lotions, shampoo, powders, suspensions and solutions.
The stable topical composition of this invention may be used treating fungal infections like dermatophytosis, mucocutaneous candidiasis, Tinea pedis, tinea corporis and tinea cruris; Candidiasis: Intertrigo and interdigital erosion, Tinea versicolor, trichophytosis, vorticosus trichophytosis, tinea profunda, trichomycosis favosa, etc., candidias such as sublimis candidias, profunda candidias, tinea nigra, sporotrichosis, chromomycosis, cryptococcosis, aspergillosis, mucormycosis, coccidioidomycosis, histoplasmosis, erythema

mycoticum infantile, intertrigo erosiva candidamycetica, erosio interdigitalis candidamycetica angulus infectious candidamyceticus, chronic mucocutaneous candidiasis or the like.
In one embodiment, the stable topical composition of the present invention is for use in treating fungal infections.
In one embodiment, the present invention relates to method of treating fungal infections using stable topical composition of the invention.
Following examples are provided to enable one skilled in the art to practice the invention and are merely illustrative of the invention. The examples should not be read as limiting the scope of the invention.
EXAMPLES
EXAMPLE 1: Luliconazole Cream (1% w/w)

Step No Ingredients Qty. in % w/w
I Purified water 75.71

Disodium edetate 0.05

Sepineo P600* 4

Medium Chain Triglyceride 8

Isopropyl Myristate 3
II Propylene Glycol 7

Butylated Hydroxy Toluene 0.1

Methylparaben 0.14
III Benzyl Alcohol 1

Luliconazole 1
Total 100
* Acrylamide/Sodium Acryloyldimethyl taurate copolymer (and) Isohexadecane (and) Polysorbate 80
Manufacturing Process
Step I: Dissolve disodium edetate in purified water, then add under slow stirring Sepineo P600 to get white gel. Then add medium chain triglyceride and isopropyl myristate.

Step II : Dissolve butylated hydroxy toluene and methylparaben in propylene
glycol at 60°C-65°C. Add this solution step to step I.
Step III: Disperse luliconazole in benzyl alcohol and add to step II
Physical Parameters:
Description : White cream
pH : 5.07
EXAMPLE 2: Luliconazole Cream (1% w/w)

Step No Ingredients Qty in % w/w
I Purified water 71.63

Disodium edetate 0.05

Sepineo P600* 4

Medium chain Triglyceride 5

Isopropyl Myristate 3
II Medium chain Triglyceride 3

Propylene Glycol 7

Butylated Hydroxy Toluene 0.1

Methylparaben 0.2
III Pharmasolve (N- methyl 2 Pyrrolidone) 5

Luliconazole 1
Total 100
Manufacturing Process:
Step I: Dissolve disodium edetate in purified water, then add under slow stirring
Sepineo P600 to get white gel. Then add medium chain triglyceride and
isopropyl myristate.
Step II : Dissolve propyl paraben and Methylparaben in medium chain
triglyceride at 60°C-65°C. Add this solution step to step I.
Step III: Dissolve butylated hydroxy toluene and methylparaben in propylene
glycol at 60°C-65°C. Add this solution step to step I.

Step IV: Dissolve luliconazole in pharmasolve to form a clear solution and add this solution to step III
Physical Parameters:
Description : White cream
pH : 5
EXAMPLE 3: Luliconazole Lotion/ Stable topical Solution (1% w/v)

Step No Ingredients Qty. in % w/v
I Hexylene Glycol 12

Medium Chain Triglyceride** 46.7

Isopropyl Myristate 35
II N-Methyl -2-Pyrrolidone (Pharmasolve) 5

Luliconazole 1
Total 100
** Caprylic /Capric Triglyceride (Crodamol CCTG)
Brief Manufacturing Process:
Step I: Mix hexylene glycol, medium chain triglyceride and isopropyl myristate.
Step II: Dissolve Luliconazole in Pharmasolve and add to step I.
Step VI: Store in a tightly closed container below 30°C.
Physical Parameters:
Description : Clear solution.
EXAMPLE 4: Luliconazole and Beclomethasone Dipropionate Cream (1% w/w & 0.025% w/w)

Step No. Ingredients Qty. in % w/w
I Purified water 70.61

Disodium edetate 0.05

Sepineo P600* 4

Medium Chain Triglyceride 8

Isopropyl Myristate 3
II Propylene Glycol 3.5

Beclomethasone Dipropionate 0.025
III Propylene Glycol 3.5

Butylated hydroxytoluene 0.1

Methylparaben 0.2

Propylparaben 0.02
IV Benzyl Alcohol 1

Pharmasolve 5

Luliconazole (Micronized) 1
Total 100
Manufacturing Process
Step I: Dissolve disodium edetate in purified water, then add under slow stirring Sepineo P600 to get white gel and then add medium chain triglyceride and isopropyl myristate.
Step II : Dissolve beclomethasone dipropionate in propylene glycol at 60°C-65°C and add this solution step to step I.
Step III: Dissolve butylated hydroxy toluene, methylparaben and propylparaben in propylene glycol at 60°C-65°C and add this solution step to step II. Step IV: Add and dissolve luliconazole in a mixture of benzyl alcohol and Pharmasolve and add to step III.
Physical Parameters:
Description : White cream
pH : 5.4
EXAMPLE 5: Luliconazole and Beclomethasone Dipropionate Cream (1% w/w & 0.025% w/w)

Step. No. Ingredients Qty. in % w/w
I Purified water 65.58

Disodium edetate 0.05

Sepineo P600* 4

Medium Chain Triglyceride 8

Isopropyl Myristate 3
II Propylene Glycol 3.5

Beclomethasone Dipropionate 0.025
III Propylene Glycol 3.5

Butylated hydroxytoluene 0.1

Methylparaben 0.2

Propylparaben 0.02
IV Benzyl Alcohol 1

Pharmasolve 5

Luliconazole (Micronized) 1
V Purified Water 5

Triethanolamine 0.02
Total 100
Manufacturing Process
Step I: Dissolve disodium edetate in purified water, then add under slow stirring Sepineo P600 to get white gel and then add medium chain triglyceride and isopropyl myristate.
Step II: Dissolve beclomethasone dipropionate in in propylene glycol at 60°C-65°C and add this solution step to step I.
Step III: Dissolve butylated hydroxy toluene, methylparaben and propylparaben in Propylene glycol at 60°C-65°C and add this solution step to step II. Step IV: Add and dissolve luliconazole in a mixture of benzyl alcohol and Pharmasolve and add to step III. Step V: Dissolve triethanolamine in purified water and add to step IV.

Physical Parameters:
Description : White cream.
pH (alcoholic Solution): 6.5
EXAMPLE 6: Luliconazole and Beclomethasone Dipropionate Cream (1% w/w & 0.025% w/w)

Step No Ingredients Qty. in % w/w
I Purified water 68.1

Disodium edetate 0.05

Sepineo P600* 4

Medium Chain Triglyceride 8

Isopropyl Myristate 3
II Propylene Glycol 3.5

Beclomethasone Dipropionate 0.025
III Propylene Glycol 3.5

Butylated hydroxytoluene 0.1

Methylparaben 0.2

Propylparaben 0.02
IV Benzyl Alcohol 1

Pharmasolve 5

Luliconazole (Micronized) 1
V Purified Water 2.5

Citric Acid Monohydrate 0.01
Total 100
Manufacturing Process
Step I: Dissolve disodium edetate in purified water, then add under slow stirring Sepineo P600 to get white gel and then add medium chain triglyceride and isopropyl myristate.

Step II: Dissolve beclomethasone dipropionate in in propylene glycol at 60°C-65°C and add this solution step to step I.
Step III: Dissolve butylated hydroxy toluene, methylparaben and propylparaben in Propylene glycol at 60°C-65°C and add this solution step to step II. Step IV: Add and dissolve luliconazole in a mixture of benzyl alcohol and Pharmasolve and add to step III. Step V: Dissolve citric acid monohydrate in purified water and add to step IV.
Physical Parameters:
Description : White cream
pH : 4.5
EXAMPLE 7: Luliconazole and Beclomethasone Dipropionate Stable topical Solution (Lotion) (1% w/v)

Step. No. Ingredients Qty. in % w/v
I Hexylene Glycol 12

Medium Chain Triglyceride** 41.95

Isopropyl Myristate 31
II N-Methyl -2-Pyrrolidone (Pharmasolve) 5

Beclomethasone Dipropionate 0.025

Luliconazole (Micronized) 1
III Medium Chain Triglyceride** q.s
Total 100
Manufacturing Process:
Step I: Mix hexylene glycol, medium chain triglyceride & isopropyl myristate.
Step II: Dissolve Beclomethasone Dipropionate and Luliconazole in Pharmasolve
and add to step I. Filter through 200# nylon cloth and make up volume with
Medium Chain Triglyceride.
Step VI: Store in a tightly closed container below 30°C.

Physical Parameters:
Description : Clear solution.
pH (alcoholic Solution): 6.5
EXAMPLE 8: Luliconazole Stable topical Powder with Allantoin (1% w/w and 0.2%w/w)

Step. No. Ingredients Qty. in % w/v
I Luliconazole 1

Allantoin 0.2

Starch (Maize Starch) 5

Talc 1.43
II Colloidal Silicon Dioxide 1

Talc 90.87

Perfume Powder 7238 0.5
Total 100
Manufacturing Process:
Step I: Weigh accurately maize starch, and dry it at 120°C for 1 hour. Mix
Luliconazole, Allantoin with maize starch, talc, mix for properly and shift through
100# sieve.
Step II: Sift powder perfume passing through 300# sieve and spray and mix
uniformly with I blend and shift the final blend through 40# sieve.
Physical Parameters:
Description : White free flowing powder.
EXAMPLE 9: Luliconazole Stable topical Powder with Allantoin (1% w/w and 0.2%w/w)

Step. No. Ingredients Qty. in % w/v
I Luliconazole 1

Allantoin 0.2

Starch (Maize Starch) 5

Talc 1.43
II Colloidal Silicon Dioxide 1

Talc 89.87

Perfume Powder 7238 1
Total 100
Manufacturing Process:
Step I: Weigh accurately maize starch, and dry it at 120°C for 1 hour. Mix
Luliconazole, Allantoin with maize starch, talc, mix for properly and shift through
100# sieve.
Step II: Sift powder perfume passing through 300# sieve and spray and mix
uniformly with I blend and shift the final blend through 40# sieve.
Physical Parameters:
Description : White free flowing powder
EXAMPLE 10: Luliconazole 1% and Selenium Sulfide 2.5% Suspension

Step. No. Ingredients Qty. in % w/v
I Purified Water 8

Citric Acid Monohydrate 0.28

Vancide 89 0.1

Gum Acacia 1.25

Selenium Sulfide 2.5
II Purified Water 12

Diethanol Amine Lauryl Sulphate (DELS) 20

Ethylene Glycol Stearates 4.4

Diethanol Amine Lauryl Sulphate (DELS) 44.4
III Diethanol Amine Lauryl Sulphate (DELS) 7

Luliconazole 1

Glycerol Mono Ricinoleate 0.9

Bouquet I.D. 14013m (Compound Id) 1
Total 100
Manufacturing Process:
Step I: Dissolved citric acid monohydrate, Vancide 89 in purified water. Add
gum acacia and allow soaking for 30 minutes. After soaking disperse in selenium
sulfide for 30 minutes. Then load bulk to boll mill for 30 minutes.
Step II : In a separate vessel take, add diethanol amine lauryl sulphate in purified
water and heat to 60°C -65°C. Add ethylene glycol stearates under stirring and
continue heating till temperature reaches to 70°C–75°C. Then add DELS slowly
to avoid precipitation of ethylene glycol stearate. Stir slowly till temperature
reaches to 40°C. Then add selenium sulfide slurry in step II.
Step III: In a separate vessel disperse luliconazole in DELS under stirring for 15
minute and transfer this phase to bulk of step II under slow stirring.
Step IV: Add glycerol mono ricinoleate to bulk of step III under stirring. Add
Bouquet ID 14013 perfume and stir for 20 minutes and record the pH.
Physical Parameters:
Description : Orange color viscous suspension
pH : 5.2
EXAMPLE 11: Luliconazole 1% Oromucosal Solution

Step. No. Ingredients Qty. in % w/v
I Propylene Glycol 85.5

Luliconazole 1
II Glycerin Refine 12.52
III Propylene Glycol q.s to 100 ml
Manufacturing Process:
Step I: Add Luliconazole in propylene glycol under stirring to get uniform

dispersion. Heat the dispersion to 65°C–70°C to get a clear solution. Step II : Add glycerin in step I under stirring to form uniform solution. Step III: Make up the volume with propylene glycol and filter the solution through 100# nylon cloth.
Physical Parameters:
Description : Clear viscous solution

Step. No. Ingredients Qty. in % w/v
I Propylene Glycol 85.5

Luliconazole 1

Sodium saccharin 0.2
II Glycerin Refine 12.52

Aniseed N Flavour 0.2
III Propylene Glycol q.s to 100 ml
Manufacturing Process:
Step I: Add Luliconazole in propylene glycol under stirring to get uniform
dispersion. Heat the dispersion to 65°C–70°C to get a clear solution. Add sodium
saccharin under stirring to get clear solution.
Step II : Add glycerin in step I under stirring to form uniform solution. Then add
under stirring at 30°C-35°C Aniseed N flavor.
Step III: Make up the volume with propylene glycol and filter the solution
through 100# nylon cloth.
Physical Parameters:
Description : Clear viscous solution
EXAMPLE 13: Luliconazole, Clobetasol propionate and Neomycin Sulphate Cream (1% w/w, 0.05% w/w & 0.5%w/w)

Step No. Ingredients Qty. in % w/w
I Cetosteryl Alcohol 8.4

Arlacel 165*** 3

White Wax 1.25

Glyceryl Monosterate (NSE) 5

Butylated Hydroxytolunene 0.1

Chlorocresol 0.075
II Purified Water 30.025

Propylene Glycol 10

Sodium Citrate anhydrous 0.05

Citric Acid monohydrate 0.05
III Propylene Glycol 26

Luliconazole 1
IV Propylene Glycol 11.5

Clobetasol Propionate 0.05
V Purified Water 3

Neomycin sulphate 0.5
Total 100
*** glycerol monosterate and Macrogaol 100 streate
Manufacturing Process
Step I: Heat cetosteryl alcohol, Arlacel 165, white wax, glyceryl monosterate (NSE), butylated hydroxytolunene, chlorocresol to 65°C -70°C, get clear phase Step II: Dissolve sodium citrate anhydrous, citric acid monohydrate in purified water, and propylene glycol, mixture at to 65°C -70°C.
Step III: Dissolve luliconazole separately in propylene glycol at to 60°C -65°C Step IV: Dissolve clobetasol propionate in in propylene glycol at 50°C-55°C. Add this solution step to step I.
Step V: Add step I in step II at 65-70°C , emulsify for 5 minutes then add step III at 65°C to emulsification, after mixing add step IV mix well. Step IV: Separately dissolve Neomycin sulphate at 40°C to get clear solution in

purified water and then add this solution to main bulk at 40°C.
Physical Parameters:
Description : White cream
pH : 5.10 (pH range 4.8 to 5.5)
EXAMPLE 14: Luliconazole, Clobetasol propionate and Neomycin Sulphate Cream (1% w/w, 0.05% w/w & 0.5%w/w)

Step. No. Ingredients Qty. in % w/w
I Purified water 60.61

Disodium EDTA 0.05
II Cetomacrogol E Wax 13.5

Liquid Paraffin 6

Glyceryl Monosterate (SE) 2

Polyoxyethyl cetyl ether (Brij 58) 1

Butylated Hydroxy Toluene 0.1

Chlorocresol 0.1
III Propylene Glycol 5

Clobetasol Propionate 0.05
IV Pharmasolve 5

Luliconazole 1
V Purified Water 2

Neomycin sulphate 0.5
VI Purified Water 3

Citric acid monohydrate 0.045

Sodium Citrate 0.045
Total 100.000
Manufacturing Process
Step I: Dissolve disodium EDTA in purified water at to 70°C -72°C

Step II: Mix Cetomacrogol E wax, liquid paraffin, glyceryl monosterate (SE),
polyoxyethyl cetyl ether (Brij 58), butylated hydroxy toluene, chlorocresol and
heat it completely to 70°C -72°C .
Step III: Ttransfer oil phase to aqueous phase, under homogenization at 70-72°C
to form emulsion.
Step IV: Dissolve clobetasol propionate in in propylene glycol at 50°C-55°C and
add this solution to step III.
Step V: Separately dissolve neomycin sulphate at 40°C to get clear solution.in
purified water and then add this solution to step IV at 40°C.
Step VI: Separately dissolve in it citric acid monohydrate and sodium citrate in
purified water to get a clear solution and add this to step V.
Physical Parameters:
Description : White cream
pH : 5.50 (pH range 5.0 to 6.5)

We claim:
1. A stable topical composition comprising luliconazole wherein the composition is free of an aliphatic alcohol and a ketone.
2. A stable topical composition of claim 1, wherein the stable topical composition further comprises one or more pharmaceutical excipients selected from a group consisting of a medium chain triglyceride, a polyhydric alcohol, and an ester of fatty acid.
3. A stable topical composition of claim 2, wherein the medium chain triglyceride is selected from medium-chain triglycerides of the olive oil, coconut oil, or palm kernel oil.
4. A stable topical composition of claim 3, wherein the medium chain alcohol is medium-chain triglycerides of coconut oil.
5. A stable topical composition of claim 2, wherein the polyhydric alcohol is selected from ethylene glycol, propylene glycol, hexylene glycol, glycerol, erythritol or sorbitol.
6. A stable topical composition of claim 5, wherein the polyhydric alcohol is propylene glycol or hexylene glycol.
7. A stable topical composition of claim 2, wherein the ester of fatty acids is selected from higher fatty acids such as oleic acid, isostearic acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, and undecylenic acid.
8. A stable topical composition of claim 7, wherein ester of fatty acid is isopropyl myristate.
9. A stable topical composition of claim 2, wherein the stable topical composition comprises caprylic /capric triglyceride, propylene glycol and isopropyl myristate.
10. A stable topical composition of claim 2, wherein the stable topical composition comprises caprylic /capric triglyceride, hexylene glycol and isopropyl myristate.
11. A stable topical composition of claims 2, wherein the stable topical composition further comprises chelating agents and a preservatives.

12. A stable topical composition of claim 1, wherein the composition comprises one or more of 0.5% -2% of luliconazole, 1%-20% of caprylic /capric triglyceride, 1%-25% of propylene glycol or hexylene glycol, 1%-10% of isopropyl myristate, 0.05%-2% of a preservative and 0.01%-1% of a chelating agent by weight of the composition.
13. A stable topical composition of claim 1, wherein the composition comprises one or more of 0.5% -2% of luliconazole, 30%-80% of caprylic /capric triglyceride, 1%-25% of propylene glycol or hexylene glycol, 15%-50% of isopropyl myristate, 0.05%-2% of a preservative and 0.01%-1% of a chelating agent by weight of the composition.
14. A stable topical composition comprising luliconazole in combination with a corticosteroid wherein; the corticosteroid is selected from a group consisting of hydrocortisone, prednisolone, dexamethasone, clobetasol, betamethasone, beclomethasone, mometasone or salts thereof.
15. A stable topical composition of claim 14 wherein the corticosteroid is beclomethasone dipropionate.
16. A stable topical composition of claim 14 wherein the corticosteroid is clobetasol propionate
17. A stable topical composition of claim 14 wherein; the composition is free of an aliphatic alcohol and a ketone.
18. A stable topical composition of claim 17, wherein the stable topical composition further comprises one or more pharmaceutical excipients selected from a group consisting of a medium chain triglyceride, a polyhydric alcohol, and an ester of fatty acid.
19. A stable topical composition of claim 18 wherein, the medium chain
triglyceride is selected from medium-chain triglycerides of the olive oil,
coconut oil, or palm kernel oil.
20. A stable topical composition of claim 19 wherein, the medium chain triglyceride is medium-chain triglycerides of coconut oil.
21. A stable topical composition of claim 18 wherein, the polyhydric alcohol is selected from ethylene glycol, propylene glycol, hexylene glycol, glycerol,

erythritol or sorbitol.
22. A stable topical composition of claim 21 wherein, the polyhydric alcohol is propylene glycol or hexylene glycol
23. A stable topical composition of claim 18 wherein, the ester of fatty acids is selected from higher fatty acids such as oleic acid, isostearic acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, and undecylenic acid.
24. A stable topical composition of claim 23 wherein, the ester of fatty acid is isopropyl myristate.
25. A stable topical composition of claim 18 wherein, the stable topical composition comprises caprylic /capric triglyceride, propylene glycol or hexylene and isopropyl myristate.
26. A stable topical composition of claim 18, wherein the stable topical composition further comprises chelating agents and a preservatives.
27. A stable topical composition of any of the preceding claims; wherein is in the
form of any of the dosage form such as gels, creams, ointments, lotions,
shampoo, powders, suspensions and solutions.
28. A stable topical composition of claim 16, wherein the composition comprises one or more of 0.5% -2% of luliconazole, 0.01%-1% of a corticosteroid, 1%-20% of caprylic /capric triglyceride, 1%-25% of propylene glycol or hexylene glycol, 1%-10% of isopropyl myristate, 0.05%-2% of a preservative and 0.01%-1% of a chelating agent by weight of the composition.
29. A stable topical composition of claim 1, wherein the composition comprises one or more of 0.5% -2% of luliconazole, 0.01%-1% of a corticosteroid, 30%-80% of caprylic /capric triglyceride, 1%-25% of propylene glycol or hexylene glycol, 15%-50% of isopropyl myristate, 0.05%-2% of a preservative and 0.01%-1% of a chelating agent by weight of the composition.
30. A stable topical composition of any of the preceding claims wherein the composition is for use in treating fungal infections.