FORM 2
THE PATENTS ACT 1970
(39 of 1970)
AND
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule l3)
1. TITLE OF THE INVENTION:
"TOPICAL MOUSSE COMPOSITION"
2. APPLICANT!
(a) NAME: CIPLA LTD.
(b)NATIONALITY: Indian Company incorporated under the Indian Companies Act, 1956
(c) ADDRESS: 289, Bellasis Road, Mumbai Central, Mumbai - 400 008, Maharashtra, India.
3. PREAMBLE TO THE DESCRIPTION:
The following specification particularly describes the invention and the manner in which it is to be formed.

Field of the Invention:
The present invention relates to a topical mousse composition for administration of mometasone, method of manufacturing the said topical composition and its use in the treatment and/or prevention of skin diseases.
Background and Prior art:
Topical corticosteroids, as a class, demonstrate anti-inflammatory, anti-pruitic and vasoconstrictive actions. Corticosteroids, particularly in the form of ester compounds, are used, inter alia, in the treatment of skin diseases in humans, such as, for example, eczema, infantile eczema, atopic dermatitis, dermatitis herpetiformis, contact dermatitis, seborrheic dermatitis, neurodermatitis, psoriasis and intertrigo.
Mometasone Furoate is a synthetic steroid having the chemical name, 9a, 21-dichloro-lip, 17-dihydroxy-]6a-methylpregna-l,4-diene-3, 20 dione 17-(2-furoate), the empirical formula C27H30CI2O6. and a molecular weight of 521.4. Mometasone furoate is a fine white powder that is insoluble in water, slightly soluble in octanol, and moderately soluble in ethyl alcohol. Commercially mometasone furoate is available as ELOCON® 1% Cream, ELOCON® 1% Lotion and ELOCON® 1% Ointment and has been indicated for relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.
Any discussion of the prior art throughout the specification should in no way be considered as an admission that such prior art is widely known or forms part of common general knowledge in the field.
U.S. Pat. No. 4,472,393 discloses 3,20-dioxo-l,4-pregnadiene-17α-ol-17-aromatic heterocyclic carboxylate compounds including mometasone furoate, pharmaceutical compositions containing said compounds and methods for the treatment and control of inflammatory conditions with said compounds.

U.S. Pat. No. 4,808,610 describes the poor solubility and efficacy of oleaginous topical creams that have mometasone furoate dissolved into propylene glycol. Additionally, the patent makes reference to a skin irritating effect of certain mometasone furoate/propylene glycol formulations.
U.S. Pat. No. 3,892,856 describes the use of corticosteroids dissolved in polyethylene glycol and emulsified into an oleaginous base.
U.S. Pat. No. 4,808,610 discloses a cream formulation of mometasone furoate.
U.S. Pat. No. 7,029,659 discloses a topical mousse composition comprising an occlusive agent, an aqueous solvent and an organic cosolvent. However even if the occlusive agent is used in the prescribed amount, its presence may result in less stable foam, and upon application, the occlusive agent would leave a greasy, sticky lather on the skin which would not be considered acceptable to the patient.
EP 0735885 discloses topical pharmaceutical compositions in the form of an ointment for treating psoriasis and other hyperkeratotic and/or scaly dermatoses which comprise mometasone furoate and salicylic acid together with specific pharmaceutically acceptable carriers.
WO 2009/063493 discloses a topical composition comprising a combination of a therapeutically effective amount of Mometasone furoate or its salts; a therapeutically effective amount of Fusidic acid or its salts; and a pharmaceutically acceptable carrier.
The prior art mostly discloses conventional topical formulations containing mometasone that have to be applied to the skin site in the form of alcoholic solution, lotion or creams. Further, lotions and creams are generally too viscous to allow efficient penetration of the active ingredient to the epidermis, and solutions have a tendency to evaporate before penetrating the epidermis. In addition conventional cream bases are irritating to the skin, particularly when long exposure is required, and the fluidity of lotions often makes the application difficult. Also, it is sometimes necessary to rub such formulations onto the

target site to enhance the penetration of the active ingredient into the epidermis, an action which may itself cause irritation to the skin.
Moreover due to the poor solubility of mometasone furoate, higher levels of steroids are necessary in the topical products that have been disclosed in the prior art and therefore the costs have been significantly higher and further has not led to the development of an efficacious, economic as well as cosmetically elegant topical formulations.
Hence there exists a need to develop a novel, efficacious, economic, cosmetically elegant topical formulation comprising mometasone for the treatment of skin disorders which need to be treated using corticosteroids.
Object of the invention:
The object of the present invention is to provide a non-irritating topical composition comprising mometasone.
Another object of the present invention is to provide a topical composition comprising mometasone with decreased inconvenience and increased ease of use for the patient.
Another object of the present invention is to provide a non-greasy topical composition comprising mometasone,
Another object of the present invention is to provide a simple manufacturing process for the topical composition comprising mometasone.
Yet another object of the present invention is to provide method of preventing or treating skin diseases such as psoriasis, atopic dermatitis and other hyperkeratotic and/or scaly dermatoses which method comprises administering to the patient in need thereof a topical composition according to the present invention.

Summary of the invention:
According to one aspect of the present invention there is provided a topical composition comprising mometasone or its pharmaceutically acceptable salts, solvates, derivatives, hydrates, anhydrates, enantiomers, polymorphs or mixtures thereof and one or more pharmaceutically acceptable excipients, wherein the topical composition is substantially free of occlusive agents.
According to another aspect of the present invention there is provided a process of manufacturing the topical composition comprising mometasone.
According to another aspect of the present invention there is provided a use of the said topical composition comprising mometasone in the manufacture of a medicament for treatment and/or prevention of skin diseases such as psoriasis, atopic dermatitis and other hyperkeratotic and/or scaly dermatoses in patients in need thereof.
According to another aspect of the present invention there is provided a method of preventing or treating skin diseases such as psoriasis, atopic dermatitis and other hyperkeratotic and/or scaly dermatoses comprising applying the topical composition of mometasone to the patients in need thereof.
Detailed Description:
As discussed above, there is a need to develop a non-irritating, efficacious, economic as well as cosmetically elegant topical formulation of mometasone which provides effective amount of mometasone to the target site on the skin.
Occlusive agents have been commonly employed in the preparation of topical compositions and are also used in an amount sufficient enough to form an occlusive layer on the target skin site. However, if these occlusive agents are not utilized, the resulting topical mousse compositions may not have the desired conditioning, cleansing and feel characteristics and if they are used, the resulting compositions may exhibit poor foam characteristics as well as be gTeasy and sticky. The inventors of the present invention have found that by adjusting the other components of the composition there can be

provided a mousse composition comprising mometasone, the said composition exhibiting the desired characteristics.
According to the present invention there is provided a topical composition comprising mometasone or its pharmaceutically acceptable salts, solvates, derivatives, hydrates. anhydrates, enantiomers. polymorphs or mixtures thereof and one or more pharmaceutically acceptable excipients, wherein the topical composition is substantially free of occlusive agents.
According to one embodiment, there is provided topical composition comprising mometasone and one or more surfactants, one or more solvents.
According to another embodiment, there is provided topical composition comprising mometasone and one or more surfactants, one or more solvents wherein the composition is substantially free of any occlusive agent.
The term "occlusive agent" that has been used throughout the description means any excipient or combination of excipients that provide an occlusive layer or hydration barrier to the skin. An occlusive layer or hydration barrier is a layer or barrier which is sufficient to result in reduction of trans-epidermal water loss, which results in skin hydration. Examples of occlusive agents are mineral oils and greases, long chain fatty acids, animal fats and greases, vegetable fats and greases, water insoluble polymers and the like.
The topical composition according to the present invention can be provided as a spray, gel, or a mousse forming skin treatment composition.
In one embodiment, the topical composition according to the present invention is provided in the form of a mousse forming skin treatment composition, wherein the composition comprises mometasone, or its pharmaceutically acceptable salts, solvates, derivatives, hydrates, anhydrates, enantiomers. polymorphs or mixtures thereof and one or more pharmaceutical!}' acceptable excipients, wherein the topical composition is substantially free of occlusive agents, and which is formulated so as to be foamable on

dispensing from a housing in which the composition can be packaged for administration to a patient.
The term "mousse" that has been used throughout the description is intended to cover a product with a pressurized foam delivery system. These compositions provide conditioning and cleansing attributes as well as produce desirable skin fee! combined with rich, creamy foam without the undesirable greasy feel which is normally associated with compositions incorporating occlusive agents.
In another embodiment, of the present invention there is provided a topical mousse composition formulated for topical application to skin, which comprises mometasone.
The terms "mometasone" is used throughout the description in broad sense to include not only the mometasone per $e but also its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable anhydrates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs and pharmaceutically acceptable prodrugs or mixtures thereof.
The amount of mometasone, present in the present invention may range from about 0.005% by weight to about 10% by weight, preferably about 0.05% to 1% by weight based on the total weight of the composition.
According to the present invention, mometasone may be in hydrate or anhydatre form.
In a further embodiment, of the present invention, the topical mousse composition comprises mometasone furoate.
The topical mousse composition according to the present invention further comprises a surfactant.

Suitable surfactants that can be employed in the topical mousse composition according to the present invention may comprise non-toxic pharmaceutically acceptable non-ionic, anionic and cationic surfactants, e.g. fatty alcohols, fatty acids and fatty acid salts thereof.
Examples of suitable non-ionic surfactants may comprise glycerol fatty acid esters such as glycerol monostearate, glycol fatty acid esters such as propylene glycol monostearate, polyhydric alcohol fatty acid esters such LIS polyethylene glycol (400) monooleate. polyoxyethyiene fatty acid esters such as polyoxyethylene (40) stearate, polyoxyethylene fatty alcohol ethers such as polyoxyethylene (20) stearyl ether, polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monostearate, sorbitan esters such as sorbitan monostearate. alkyl glycosides such as cetearyl giucoside, fatty acid ethanolamides and their derivatives such as the diethanolamide of stearic acid, and the like.
Examples of suitable anionic surfactants may comprise soaps including alkali soaps, such as sodium, potassium and ammonium salts of aliphatic carboxylic acids, usually fatty acids, such as sodium stearate. Organic amine soaps, also included, include organic amine salts of aliphatic carboxylic acids, usually fatty acids, such as triethanolamine stearate. Another class of suitable soaps is the metallic soaps, salts of polyvalent metals and aliphatic carboxylic acids, usually fatty acids, such as aluminium stearate. Other classes of suitable anionic surfactants include sulfated fatty acid alcohols such as sodium lauryl sulfate, sulfated oils such as the sulfuric ester of ricinoleic acid disodium salt, and sulfonated compounds such as alkyl sulfonates including sodium cetane sulfonate, amide sulfonates such as sodium N-methyl-N-oleyl laurate, sulfonated dibasic acid esters such as sodium dioctyl sulfosuccinate, alkyl aryl sulfonates such as sodium dodecylbenzene sulfonate, alkyl naphthalene sulfonates such a sodium isopropyl naphthalene sulfonate. petroleum sulfonate such as aryl napthalene with alkyl substitutes.
Examples of suitable cationic surfactants may comprise amine salts such as octadecyl ammonium chloride, quarternary ammonium compounds such as benzalkonium chloride.
In one embodiment the surfactants in the topical mousse composition according to the present invention are non-ionic surfactants (emulsifying waxes) which may comprise

ethoxylated fatty alcohols, i.e., those having a saturated hydrocarbon chain length of C16 to C18 and a suitable polyoxyethylene chain length, i.e., less than 10. Specific ethoxylated fatty alcohols include polyoxyethylene stearyl ether (sold under the tradename Brij 72 by IC1 Americas, Wilmington, Del.) and polyoxyethylene cetyl ether (sold under the tradename Brij 52 by IC1 Americas, Wilmington, Del), mixtures of ethoxylated fatty alcohols including ethoxylated fatty alcohols, mixtures of ethoxylated fatty alcohols and phosphate esters (such as those available under the tradename Crodaphos SG from Croda, Inc., New York, N.Y.), mixtures of ethoxylated fatty alcohols with mixtures of fatty alcohols and ethoxylated sorbitan esters (such as those available under the tradename Polawax A31 from Croda, Inc., New York, N.Y.) and mixtures of ethoxylated fatty alcohols with silicone surfactants (such as those available under the tradename Dow Corning 193 Silicone Surfactant from Dow Corning Corp., Midland, Mich),
Surfactants may be present in an amount from, approximately 1% to 15% by weight based on the total weight of the topical mousse composition, preferably in an amount to adjust the aforesaid percent weight of the surfactant, aqueous solvent and organic solvent mixture.
The topical mousse composition according to the present invention further comprises a propellant.
Propellants are utilized to cause an expulsion of the ingredients of the composition from a housing containing the same after administration of the said composition to the patient.
Suitable propellants that can be employed in the topical mousse composition according to the present invention may comprise any suitable gas, such as a hydrocarbon, e.g. propane, butane, CFCs, HFCs, nitrogen or air. Typically the propellant may be selected from the group consisting of 1,1,1,2-tetrafluoroethane (HFA 134a), 1,1,1,2,3,3,3-heptafluoroethane (HFA 227), a combination of 1,1,1,2-tetrafluoroethane and 1,1,1,2,3,3,3-heptafluoroethane, monofluorotrichloromethane and dichlorodifluoromethane, and derivatives thereof, in particular 1,1,1,2-tetrafluoroethane (HFA 134a) or 1,1,1,2,3,3,3-heptafluoroethane (HFA 227).

Propellant may be present in the topical mousse composition of the present invention in an amount, from about 2.5% to 25% by weight, preferably 5% to 15% by weight, based on the total weight of the topical mousse composition. The propellant may be introduced into the mousse composition at the time of filling the container, utilizing for example a standard aerosol dispenser, e.g. a spray can arrangement.
The topical mousse composition according to the present invention further comprises one or more solvents.
Solvents according to the present invention may comprise one or more aqueous solvents and/or one or more organic solvents.
Aqueous solvent may be present in an amount from about 25% to 95% by weight, preferably about 40% to 90% by weight, based on the total weight of the pharmaceutical mousse composition
Suitable aqueous solvents according to the present may comprise water. Suitable organic solvent that can be employed in the topical mousse composition of the present invention may comprise an ester of a fatty acid for example a C12-C15 alkyl benzoate, a medium to long chain alcohol, an aromatic and/or alkyl pyrrolidinone, an aromatic and/or alkyl, and/or cyclic ketone, an aromatic and/or alkyl, and/or cyclic ether, substituted and/or unsubstituted single or multiple ring aromatic, straight chain and/or branched chain and/or cyclic alkane or silicone. The organic solvent may be present in amounts of approximately 20% to 75% by weight based on the total weight of the topical mousse composition.
Suitable humectants may also be employed in the topical mousse composition of the present invention, which may comprise polyhydric alcohols such as glycols, and polysaccharides, such as ethylene glycol, propylene glycol, butylene glycol, diethylene glycol, dipropylene glycol, glycerin, diglycerin, sorbitol, malvitol, trehalose, raffinose, xylitol, mannitol, polyethylene glycol, propylene glycol, polyglycerin, cholesterol, squaline, fatty acids, octyldodecanol, myristyl alcohol, urea, lanolin, lactic acid, esters

such as isopropyl stearate, isopropyl myristate, isopropyl palmitate and isopropyl laurate and the like.
The topical mousse composition according to the present invention may also include further ingredients which are suitably used in skin care treatment compositions, and such ingredients may include preservatives, stabilizers, antioxidants, pH adjusting agents, skin penetration enhancers, and viscosity modifying agents such as petrolatum, waxes, lanolin, vegetable and mineral oils, plasticizers, preservatives, colorants, fragrances or other suitable ingredients required for the formulation of a topical mousse composition.
Alternatively, the topical mousse composition of the present invention comprising mometasone may further comprise one or more suitable biologically active agents, which may comprise one or more pharmaceutical agents, an oxygen carrier, a nutrient, a coagulant, a nucleic acid molecule, a nucleic acid vector, an antisense nucleic acid, a ribozyme, a contrast agent, diagnostic agent or a pheromone. Preferably the selected additional active agent may be suitable for treating skin diseases such as psoriasis and other hyperkeratotic and/or scaly dermatoses.
The present invention further provides a process of manufacturing the topical mousse composition according to the present invention which process comprises providing mometasone or its pharmaceutically acceptable salts, solvates, derivatives, hydrates, anhydrates, enantiomers, polymorphs or mixtures thereof, in the form of a composition suitable for topical administration to the skin.
Suitably the process for manufacturing the topical mousse composition according to the present invention comprises:
(1) Mixing mometasone, surfactant, organic solvent and aqueous solvent and optionally humectant
(2) Filing the above mixture in can and finally charging the can with propellant and crimping the can.

It will be appreciated to the skilled artisan that the process of manufacturing the above mentioned topical mousse composition can also be modified or manufactured in a manner according to known methods in the art.
The present invention also provides a topical mousse composition substantially as hereinbefore described packaged in a housing (typically a can), provided with a dispensing mechanism for dispensing said composition to the skin, hair or scalp of a patient. Preferably the dispensing mechanism and the ingredients of a composition according to the present invention are such that a mousse can be generated on dispensing from the housing.
According to another aspect of the present invention there is provided a skin treatment product, substantially as hereinbefore described packaged in a housing (typically a can), provided with a dispensing mechanism for dispensing said composition to the skin, hair and scalp of a patient.
The present invention further provides use of the topical mousse composition comprising mometasone for the treatment and/or prevention of psoriasis and other hyperkeratotic and/or scaly dermatoses.
The term "treatment and/or prevention of psoriasis and other hyperkeratotic and/or scaly dermatoses" that has been mentioned throughout the description means producing a therapeutic response or improvement in the overall disease condition as well as associated signs which include inflammation, erythema, scaling, induration or lesions in mammals especially man afflicted with psoriasis and other hyperkeratotic and/or scaly dermatologic diseases.
The present invention further provides use of the topical mousse composition comprising mometasone according to the present invention for the treatment or prevention of skin diseases such as psoriasis, atopic dermatitis and other hyperkeratotic and/or scaly dermatoses.

Thus, the present invention also provides a method of preventing or treating the skin diseases such as psoriasis, atopic dermatitis and other hyperkeratotic and/or scaly dermatoses comprising application of the topical mousse composition comprising mometasone to the patients in need thereof.
The following example is for the purpose of illustration of the invention only and is not intended in any way to limit the scope of the present invention.
Examples:
Formula 1: Mometasone mousse

SrNo. Ingredients Qry (% w/w)
1 Mometasone Furoate 0.10
2 Polawax A 31 4.50
3 Glycerin 1.10
4 Ethanol 52.40
5 Purified water 31.00
6 Propellant (Propane/Butane) 10.00
Process:
(1) Mometasone furoate, polawax A31, glycerin, ethanol, water are mixed and warmed if necessary.
(2) Delivery can was filled with above mixture, charged with propellant and crimped.
It will be readily apparent to one skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the spirit of the invention. Thus, it should be understood that although the present invention has been specifically disclosed by the preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and such modifications and variations are considered to be falling within the scope of the invention.

It is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of "including," "comprising," or "having" and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items.
It must be noted that, as used in this specification and the appended claims, the singular forms "a," "an" and "the" include plural references unless the context clearly dictates otherwise. Thus, for example, reference to "a polymer" includes a single polymer as well as two or more different polymers; reference to a "plasticizer" refers to a single plasticizer or to combinations of two or more plasticizer, and the like.

We Claim,
1. A topical composition comprising mometasone or its pharmaceutically acceptable salts, solvates, derivatives, hydrates, anhydrates, enantiomers, polymorphs- or mixtures thereof and one or more pharmaceuticaily acceptable excipients.
2. A topical composition as claimed in claim 1, wherein said mometasone is in the hydrated or anhydrous form.
3. A topical composition as claimed in claim 1 or 2, wherein the said salt of mometasone is Mometasone furoate.
4. A topical composition as claimed in any of the preceding claims further comprising a surfactant.
5. A topical composition as claimed in claim 4 wherein the surfactant is selected from non-ionic, anionic and cationic surfactants.
6. A topical composition as claimed in any of the preceding claims further comprising a solvent.
7. A topical composition as claimed in claim 6, wherein the solvent is an aqueous or organic solvent.
8. A topical composition as claimed in any of the preceding claims further comprises atleast one propellant.
9. A topical composition claimed in any of the preceding claims which is in the form of mousse.
10. A topical composition as claimed in any of the preceding claims comprising mometasone or its pharmaceuticaily acceptable salts, solvates, derivatives, hydrates, anhydrates, enantiomers, polymorphs or mixtures thereof and one or

more pharmaceutically acceptable excipients, wherein the topical composition is substantially free of occlusive agents.
11. A topical composition claimed in any of the preceding claims further comprising a humectant.
12. A topical composition as claimed in any of the preceding claims, which further comprises one or more preservatives, stabilizers, antioxidants, pH adjusting agents, skin penetration enhancers, viscosity modifying agents, plasticizers, preservatives, colorants, fragrances.
13. A topical composition comprising mometasone or its pharmaceutically acceptable salts, solvates, derivatives, hydrates, anhydrates, enantiomers, polymorphs or mixtures thereof and one or more pharmaceutically acceptable excipients, wherein the topical composition is substantially free of occlusive agents and wherein said composition is further characterized as being provided as a mousse composition for skin treatment formulated so as to be foamable on dispensing from a housing in which the composition is packaged.
14. A process for preparing a topical composition as claimed in any of the preceding claims, which process comprises providing mometasone or its pharmaceutically acceptable salts, solvates, derivatives, hydrates, anhydrates, enantiomers, polymorphs or mixtures thereof, in the form of a composition suitable for topical administration to the skin.
15. A skin treatment product, which comprises a composition as claimed in claims 1 to 13 packaged in a housing provided with a dispensing mechanism for dispensing said composition to the skin of the patient.
16. A product as claimed in claim 15, wherein the said dispensing mechanism, and ingredients of said composition are such that a mousse is generated on dispensing from the housing.

17. A topical mousse composition substantially herein described with reference to the accompanying examples.