Claims:We Claim:

1. A thermostable, non-emulsified, alcohol-free, aqueous, foamable pharmaceutical composition comprising clobetasol or pharmaceutically acceptable salt thereof, atleast one C4-C6 glycol and two or more surfactants.

2. The pharmaceutical composition according to claim 1, wherein surfactants are non-ionic surfactants.

3. The pharmaceutical composition according to claim 1, wherein C4-C6 glycol is hexylene glycol and two or more non-ionic surfactants are Ceteareth and Polysorbate.

4. The pharmaceutical composition according to claim 3, wherein Polysorbate and Ceteareth are in the ratio of about 1:2 to 1:10, preferably about 1:8.

5. The pharmaceutical composition according to any of the preceding claims, wherein the composition remains stable at least for 3 minutes at 40°C after dispensing.

6. The pharmaceutical composition according to claim 1 further comprises of one or more pharmaceutically acceptable excipient(s), wherein pharmaceutically acceptable excipient(s) are selected from humectant, buffering agent, antimicrobial agent, film forming agent, foam adjuvants, vehicle and propellant.

7. A thermostable, non-emulsified, alcohol free, aqueous, foamable pharmaceutical composition consisting of 0.02% to 1% of clobetasol propionate, 5.0 to 50% w/w of hexylene glycol, 0.10 to 20% w/w of surfactants selected from polysorbate and ceteareth, 1 to 50% w/w of glycerine, 0.05 to 0.5 % w/w of citric acid and potassium citrate, 0.1 to 1.5 % w/w of phenoxyethanol, 1 to 15% w/w of polyvinyl pyrrolidone, 0.1-30% of cetyl alcohol, water and propellant.

8. A thermostable, non-emulsified, alcohol free, aqueous, foamable pharmaceutical composition comprising of 0.05% w/w of clobetasol propionate, 8% w/w of hexylene glycol, 0.6% w/w polysorbate and 5% w/w of ceteareth, 10% w/w of glycerine, 0.1 % w/w of citric acid and potassium citrate, 1 % w/w of phenoxyethanol, 2% w/w of polyvinyl pyrrolidone, 0.2% of cetyl alcohol, water and propellant.

9. A process for preparation of the foamable pharmaceutical composition comprising clobetasol or pharmaceutically acceptable salt thereof, atleast one C4-C6 glycol, two or more surfactants, and/or one or more pharmaceutically acceptable excipient(s) comprising steps

(a) Preparing aqueous solution by optionally dissolving one or more pharmaceutically acceptable excipient(s)
(b) Preparing solution by dissolving clobetasol or pharmaceutically acceptable salt thereof, atleast two surfactants and optionally one or more pharmaceutically acceptable excipient(s) in C4-C6 glycol
(c) Preparing a single phase composition by mixing solution prepared in step (a) and (b)
(d) Adding a suitable propellant to the single phase composition prepared in step (c).

10. A thermostable, non-emulsified, alcohol-free, aqueous, foamable pharmaceutical composition comprising clobetasol or pharmaceutically acceptable salt thereof and process of its preparation as herein described with reference to the examples provided in the specification.
, Description:Alcohol-free foamable pharmaceutical composition of Clobetasol

Field of the Invention

Present invention relates to a thermostable, non-emulsified, alcohol free, aqueous, foamable pharmaceutical composition comprising clobetasol or pharmaceutically acceptable salt thereof, particularly clobetasol propionate and one or more pharmaceutically acceptable excipient(s).

Background of the Invention:
Clobetasol propionate is (11b,16b)-21-chloro-9-fluoro-11-hydroxy-16-methyl-17 (1- oxopropoxy)-pregna-1,4-diene-3,20-dione, which reduces the inflammation, redness, swelling, itching, and tenderness associated with dermatologic conditions such as psoriasis.

Psoriasis is characterized by skin cells that multiply up to 10 times faster than normal. When these cells reach the surface and die, red plaques covered with white scales form. Although psoriatic plaques can be limited to only a few small areas, the condition can involve widespread areas of skin anywhere on the body. Common psoriasis symptoms can include red patches of skin covered with silvery scales, small scaling spots, dry cracked skin, itching, burning or soreness, itchy plaques, small bleeding points when scale is peeled away.

Clobetasol is approved in various forms for topical application such as topical cream, lotion, shampoo, gel, solution, ointment, spray and foam. The foam has advantage among all available forms as desired quantity of the composition can be applied at desired site without extensive rubbing and it spreads effectively because of its good flow properties for application on larger surface area. There are two types of foam based formulations of clobetasol approved, Olux® and Olux E®.

Olux is an alcohol based foamable composition comprising about 60% alcohol. An alcohol based composition has disadvantage that quick evaporation of alcohol leaves the skin dry and cracked. Thus, for conditions like psoriasis, it is not desirable to apply an alcohol based composition. Further, dispensing of Olux directly onto hands is not recommended, as the foam begin to melt immediately upon contact with warm skin. Therefore, application of foam on affected area becomes difficult.

Olux E® is an emulsion based composition of clobetasol comprising oily components such as mineral oil and petrolatum. Emulsion based systems are formed by mixing water and oily components leading to a biphasic system which is less stable and requires storage under controlled temperature conditions between 20°C and 25°C. Also, emulsion based formulations are not patient compliant because it leaves an oily residue after application of composition. Oily component, specifically petrolatum and mineral oil, form an undesirable sticky and greasy layer over skin which is unacceptable for the consumer. Moreover, preparation of an emulsion based foamable composition involves expensive and tedious process and more risk factors.

Thus, there is a need for an improved foamable pharmaceutical composition which overcomes all the mentioned problems with desired therapeutic effect.

Therefore, present invention provides a thermostable, non-emulsified alcohol free, aqueous, foamable pharmaceutical composition comprising clobetasol or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipient(s).

Summary of the Invention:

One aspect of the present invention is to provide a thermostable, non-emulsified alcohol-free, aqueous, foamable pharmaceutical composition comprising clobetasol or pharmaceutically acceptable salt thereof, atleast one C4-C6 glycol and two or more surfactants.

Another aspect of the present invention provides a thermostable, non-emulsified alcohol free, aqueous, foamable pharmaceutical composition comprising clobetasol or pharmaceutically acceptable salt thereof, atleast one C4-C6 glycol, two or more non-ionic surfactants and optionally one or more pharmaceutically acceptable excipient(s), wherein the composition remains stable at least for 3 minutes at 40°C after dispensing.

Another aspect of present invention provides process for preparation of a thermostable, non-emulsified, alcohol-free, aqueous, foamable pharmaceutical composition comprising clobetasol or pharmaceutically acceptable salt thereof, atleast one C4-C6 glycol and two or more surfactants.

Detailed description of the Invention:

The following paragraphs detail various embodiments of the invention. For the avoidance of doubt, it is specifically intended that any particular feature(s) described individually in any one of these paragraphs (or part thereof) may be combined with one or more other features described in one or more of the remaining paragraphs (or part thereof). In other words, it is explicitly intended that the features described below individually in each paragraph (or part thereof) represent important aspects of the invention that may be taken in isolation and combined with other important aspects of the invention described elsewhere within this specification as a whole, and including the examples and figures. The skilled person will appreciate that the invention extends to such combinations of features and that these have not been recited in detail here in the interests of brevity.

The use of the terms “a” and “an” and “the” and similar references in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context.

The term “alcohol free” as used herein means a composition which is substantially free of lower aliphatic alcohols, such as C1-C6 alcohol including methyl, ethyl, isopropyl and butyl alcohol. The total content of alcohol in said composition is less than 5%, preferably less than 3%, most preferably, less than 1%.

The term “clobetasol” as used herein includes clobetasol or its pharmaceutically acceptable salt, preferably clobetasol is clobetasol propionate.

The term “single phase” or “non-emulsified” as used herein means the composition in prepared by mixing two or more substances and does not form two separate phases or an emulsion.

The term “aqueous” as used herein refers to the composition comprising water and is devoid of any aprotic polar solvent selected from dimethyl sulfoxide (DMSO), dimethylformamide (DMF), acetonitrle, acetone, methyl ethyl ketone, 1 ,4-Dioxane and tetrahydrofuran (THF), N-methylpyrrolidone, pyridine, piperidine, dimethyl ether, hexamethylphosphorotriamide, dimethylformamide, methyl dodecyl sulfoxide, N- methyl-2-pyrrolidone and 1 -methyl-2-pyrrolidinone) and azone (1- dodecylazacycloheptan-2-one).
The percentage “%” of the component as used herein means percent by weight of the total composition without propellant; whereas the % of propellant or propellant system as used herein means percent by weight of propellant in addition to % w/w of the total composition.

The term “foamable” as used herein includes a pharmaceutical composition capable of forming foam upon delivery.

The term “foam forming dispensing system” as used herein includes an assembly of container and aerosol valve capable of delivering foamable composition.

The present invention relates to a thermostable, non-emulsified, aqueous foamable composition of Clobetasol or its pharmaceutically acceptable salt which is devoid of alcohol and oily or greasy excipients, stable and provides improved patient compliance.

Present invention provides a thermostable, non-emulsified, alcohol free, aqueous foamable pharmaceutical composition comprising clobetasol or pharmaceutically acceptable salt thereof, atleast one C4-C6 glycol and two or more surfactants.

Marketed foam of Clobetasol propionate is either emulsion based composition or alcohol based composition. Emulsion based compositions comprise oily components leading to greasiness and tackiness on skin which is not undesirable for the patients; while alcohol based compositions, wherein alcohol provides quick breaking of foam, begin to melt immediately on contact with warm skin and hence it is not advisable to dole it on hands unless hands are the affected areas. Since, the foam is temperature sensitive, it is essential for the patient to ensure cool conditions before dispensing the foam, which is difficult in high temperature area like India. Surprisingly, it was found by inventors that the alcohol free, thermostable, quick breaking foam of present invention comprising clobetasol propionate remains stable for more than 3 minutes upon dispensing at temperature about 40°C. The foam so dispensed breaks upon applying shear force during its application. Also, present invention solves the problems associated with prior art such as irritation after application, dry skin after alcohol evaporation on application of alcohol based composition or oily residue left on application of emulsion based compositions.

Thus, one embodiment of the present invention provides a thermostable, non-emulsified, alcohol-free, aqueous, foamable pharmaceutical composition comprising clobetasol or pharmaceutically acceptable salt thereof, atleast one C4-C6 glycol and two or more surfactants.

Another embodiment of the present invention provides a thermostable, non-emulsified, alcohol free, aqueous, foamable pharmaceutical composition comprising clobetasol or pharmaceutically acceptable salt thereof, atleast one C4-C6 glycol and two or more non-ionic surfactants.

Another embodiment of the present invention provides a thermostable, non-emulsified, alcohol free, aqueous, foamable pharmaceutical composition comprising clobetasol or pharmaceutically acceptable salt thereof, atleast one C4-C6 glycol preferably hexylene glycol and atleast two non-ionic surfactants preferably Ceteareth and Polysorbate; preferably Ceteareth 20 and Polysorbate 60.

Another embodiment of the present invention provides a thermostable, non-emulsified, alcohol free, aqueous, foamable pharmaceutical composition comprising clobetasol or pharmaceutically acceptable salt thereof, hexylene glycol and atleast two non-ionic surfactants, Ceteareth-20 and Polysorbate 60, wherein Polysorbate 60 and Ceteareth-20 and are in the ratio of about 1:2 to 1:10, preferably about 1:8.
Another embodiment of the present invention provides a thermostable, non-emulsified, alcohol free, aqueous, foamable pharmaceutical composition comprising clobetasol or pharmaceutically acceptable salt thereof, atleast one C4-C6 glycol, two or more non-ionic surfactants and one or more pharmaceutically acceptable excipient(s), wherein the composition remains stable at least for 3 minutes at 40°C after dispensing.

Another embodiment of the present invention provides a thermostable, non-emulsified, alcohol free, aqueous, foamable pharmaceutical composition comprising clobetasol or pharmaceutically acceptable salt thereof, atleast one C4-C6 glycol preferably hexylene glycol and atleast two non-ionic surfactants preferably Ceteareth and Polysorbate, wherein the composition remains stable at least for 3 minutes at 40°C after dispensing.

A preferred embodiment of the present invention provides thermostable, non-emulsified, alcohol free, aqueous, foamable pharmaceutical composition comprising clobetasol or pharmaceutically acceptable salt thereof, atleast one C4-C6 glycol, two or more surfactants and optionally one or more pharmaceutically acceptable excipients; wherein clobetasol propionate is present in range of 0.02% to 1%, preferably 0.05% of the total composition; C4-C6 glycol is present in range of 5.0 to 50% w/w, preferably hexylene glycol (2-methyl-2,4-pentanediol) about 8.0 to 12.0% w/w of the total composition; two or more surfactants preferably non-ionic surfactants are present in the range of 0.10 to 20% w/w, preferably ceteareth-20 about 2 to 8% w/w and Polysorbate 60 about 0.1 to 6% w/w of the total composition. The pharmaceutically acceptable excipients comprise humectant in the range of 1 to 50% w/w, preferably glycerin in the range of 5 to 15 % w/w of the total composition; buffering agent in the range of 0.05 to 0.5 % w/w, preferably citric acid and potassium citrate at 0.1% w/w of the total composition; antimicrobial agent in the range of 0.1 to 1.5 % w/w, preferably phenoxyethanol at 1% w/w of the total composition; film forming agent in the range of 1 to 15% w/w, preferably polyvinyl pyrrolidone at 2% w/w of the total composition. The pharmaceutically acceptable excipients may further comprise a foam adjuvant, a solubilizer, a penetration enhancer, an antioxidant, a pH modifier. The said pharmaceutical composition further comprises a vehicle and a propellant system.

Another preferred embodiment of present invention provides a thermostable, non-emulsified, alcohol free, aqueous, foamable pharmaceutical composition consisting of 0.02% to 1% of clobetasol propionate, 5.0 to 50% w/w of hexylene glycol, 0.10 to 20% w/w of surfactants selected from polysorbate and ceteareth, 1 to 50% w/w of glycerine, 0.05 to 0.5 % w/w of citric acid and potassium citrate, 0.1 to 1.5 % w/w of phenoxyethanol, 1 to 15% w/w of polyvinyl pyrrolidone, 0.1-30% of cetyl alcohol, water and propellant.

Another preferred embodiment of present invention provides a thermostable, non-emulsified, alcohol free, aqueous, foamable pharmaceutical composition consisting of 0.02% to 1% of clobetasol propionate, 5.0 to 50% w/w of hexylene glycol, 0.10 to 20% w/w of surfactants selected from polysorbate and ceteareth, 1 to 50% w/w of glycerine, 0.05 to 0.5 % w/w of citric acid and potassium citrate, 0.1 to 1.5 % w/w of phenoxyethanol, 1 to 15% w/w of polyvinyl pyrrolidone, 0.05 to 5% of diethylene glycol monoethyl ether, water and propellant.

Another preferred embodiment of present invention provides a thermostable, non-emulsified, alcohol free, aqueous, foamable pharmaceutical composition comprising of 0.05% w/w clobetasol propionate, 8% w/w of hexylene glycol, 0.6% w/w polysorbate and 5% w/w of ceteareth, 10% w/w of glycerine, 0.1 % w/w of citric acid and potassium citrate, 1% w/w of phenoxyethanol, 2% w/w of polyvinyl pyrrolidone, 0.2% of cetyl alcohol, water and propellant.

Another preferred embodiment of present invention provides a thermostable, non-emulsified, alcohol free, aqueous, foamable pharmaceutical composition comprising of 0.05% w/w of clobetasol propionate, 12% w/w of hexylene glycol, 0.6% w/w polysorbate and 5% w/w of ceteareth, 5% w/w of glycerine, 0.1 % w/w of citric acid and potassium citrate, 1 % w/w of phenoxyethanol, 2% w/w of polyvinyl pyrrolidone, 2% of diethylene glycol monoethyl ether, water and propellant.

The alcohol-free, non-emulsified, aqueous system of present invention does not provide a greasy or oily residue after its application on affected area. Moreover, present composition can be prepared without involving complex steps of preparing emulsion. Other advantages of present invention over emulsion based formulation include quick onset of action as partitioning from aqueous phase to skin lipid is faster, storage temperature can be flexible, cost effective and more stability.

The present invention provides a process for preparation of thermostable, non-emulsified, alcohol free, aqueous, foamable pharmaceutical composition comprising clobetasol or pharmaceutically acceptable salt thereof, atleast one C4-C6 glycol and two or more surfactants.

Another embodiment of the present invention provides a process of preparation of the foamable pharmaceutical composition according to present invention comprising:
(a) Preparing aqueous solution by optionally dissolving one or more pharmaceutically acceptable excipient(s)
(b) Preparing solution by dissolving clobetasol or pharmaceutically acceptable salt thereof, atleast two surfactants and optionally one or more pharmaceutically acceptable excipient(s) in C4-C6 glycol.
(c) Preparing a single phase composition by mixing solution prepared in step (a) and (b)
(d) Adding a suitable propellant to the single phase composition prepared in step (c).

A preferred embodiment of the present invention provides a process of preparation of the foamable pharmaceutical composition according to present invention comprises steps:
(a) Preparing aqueous solution by dissolving one or more pharmaceutically acceptable excipient(s) selected from film forming agent, humectant and/or buffering agent
(b) Preparing solution by dissolving clobetasol or pharmaceutically acceptable salt thereof, atleast two surfactants, preferably non-ionic surfactants and one or more pharmaceutically acceptable excipient(s) selected from foam adjuvant, penetration enhancer and/or antimicrobial agent in atleast one C4-C6 glycol
(c) Preparing a single phase composition by mixing solution prepared in step (a) and (b)
(d) Adding a suitable propellant which includes liquefied and/or compressed gas to the single phase composition prepared in step (c).

Another preferred embodiment of the present invention provides a process of preparation of the foamable pharmaceutical composition according to present invention comprises steps:
(a) Preparing aqueous solution by dissolving polyvinyl pyrrolidone, glycerin, citric acid and/or Potassium citrate.
(b) Preparing solution by dissolving clobetasol or pharmaceutically acceptable salt thereof, ceteareth-20, polysorbate 60, diethylene glycol monoethyl ether (Transcutol) and/or phenoxyethanol in hexylene glycol
(c) Preparing a single phase composition by mixing solution prepared in step (a) and (b)
(d) Adding deodorized liquefied n-butane and/or propane gas to the single phase composition prepared in step (c).

The prepared foamable pharmaceutical composition is further filled into aluminum cans along with propellant.

Clobetasol or its pharmaceutically acceptable salt is present in the composition prepared according to present invention in the range of 0.02% to 1%, preferably 0.05% w/w of the total composition.

Pharmaceutical composition according to present invention may further comprise one or more pharmaceutically acceptable excipient such as foam stabilizer/foam adjuvant, humectant, solubilizer, antimicrobial agents, film forming agent, pH modifiers, buffering agents and/or penetration enhancers. Any of such excipients may be used alone or in combination of same/other excipients.

Penetration enhancers according to the present invention includes but not limited to polyoxy ethylene-2-stearly ether; terpenes such as Thymol, Menthol, Menthone, Carvacrol, Cineole, limonene; urea, sorbitol, mannitol, oligosaccharides, dimethyl isosorbide, monooleate of ethoxylated glycerides (with 8 to 10 ethylene oxide units), polyethylene glycol 200-600, Alpha-Tocopherol Polyethylene glycol succinate (Vitamin E-TPGS), transcutol (diethylene glycol monoethyl ether), glycofurol (tetrahydrofurfuryl alcohol PEG ether) or mixtures thereof. Preferably, diethylene glycol monoethyl ether (Transcutol) is used. The penetration enhancer(s) may be present in an amount ranging from 0.05 to 5%, preferably 0.1 to 3% w/w of the composition. Preferably, diethylene glycol monoethyl ether (Transcutol) is used as penetration enhancers in an amount of 2 % w/w of the composition.

Surfactants according to the present invention includes but not limited to anionic, cationic, non-ionic and/or amphoteric surfactants. Non limiting examples include anionic sufactants such as sodium lauryl sulfate, ammonium lauryl sulfate, sodium lauryl ether sulfate, triethylamine lauryl sulfate, triethanolamine lauryl sulfate, monoethanolamine lauryl sulfate, docusate sodium, and / or potassium lauryl sulfate; cationic surfactants such as cetrimonium bromide, Benzalkonium chloride and/ or stearyl dimethylbenzyl ammonium chloride; non-ionic surfactants such as fatty alcohols, cetyl alcohol, stearyl alcohol, cetostearyl alcohol, oleyl alcohol, Polyoxyethylene glycol sorbitan alkyl esters (Polysorbate, Tween), Sorbitan alkyl esters (Spans), Block copolymers of polyethylene glycol and polypropylene glycol (Poloxamers), polyoxyethylene lauryl amine, PEG-distearate, PEG-hydroxystearate, propylene glycol monostearate; Polyoxyethylene glycol alkyl ethers (Brij) such as polyoxyethylene butyl ether, polyoxyethylene cetyl ether, Polyethyleneglycol cetyl/stearyl ether (Ceteareth), polyoxyethylene oleyl cetyl ether, polyoxyethylene oleyl ether, laureth-4 and / or polyoxyethylene lauryl ether. Preferably non-ionic surfactants including ceteareth and Polysorbate, most preferably ceteareth-20 and polysorbate 60 are used. Surfactants according to the present invention may be present in an amount ranging from 0.5-25 % w/w of the composition. Preferably, non-ionic surfactants are used in the range of 0.1 to 20 % w/w of the composition. Preferably, ceteareth is used in the range of 2 to 8% w/w and Polysorbate is used in the range of 0.1 to 1% w/w of the total composition.
The ratio of Polysorbate 60 to ceteareth-20 in the foamable composition according to the present invention largely impacts its quality attributes such as foam stability at higher temperature. The ratio of polysorbate 60 to ceteareth-20 as used herein varies from about 1:2 to 1:10. Preferably, polysorbate 60 and ceteareth 20 are present in the ratio of about 1:8.

Foam adjuvant according to the present invention includes fatty alcohols having 15 or more carbon atoms in their carbon chain. The foam adjuvant is selected from cetyl alcohol, stearyl alcohol, arachidyl alcohol, behenyl alcohol, 1-triacontanol or mixtures thereof. Pharmaceutical composition comprises foam adjuvant/s in the range of 0.10 to 30%; Preferred foam adjuvant/s used are cetyl alcohol, preferably in range of 0.1 to 0.5% w/w of the total composition, most preferably 0.2% w/w of the total composition.

Humectant according to the present invention is selected from glycerol (glycerin), cetyl palmitate, PPG-15 stearyl ether, C12-C15 alkyl benzoates, dimethicone, allantoin and glycyrrhetinic acid. Pharmaceutical composition comprises humectants/s in range of 1 to 50% w/w of the total composition, preferably glycerin in range of 5 to 15% w/w of the total composition.

Film forming agents according to the present invention include but not limited to hydroxypropyl methyl cellulose (Hypromellose), hydroxypropyl cellulose, polyvinyl pyrrolidone (PVP), gelatin, polyethylene oxide, hydroxyethyl cellulose, sodium alginate and mixture thereof. Preferably, PVP-K30 is used. Film forming agent is present in an amount ranging from 1-15 % w/w of the composition. Preferably, polyvinyl pyrrolidone is present in an amount of about 2 % w/w of the composition.

An alcohol-free composition of the present invention comprises a foam generator, such as propellant. Propellants according to the present invention includes but not limited to chlorofluorocarbons such as Trichloromonofluoromethane, Dichlorodifluoromethane, Dichlorotetrafluoroethane; hydrocarbons such as propane, butane, isopropane; hydrochlorofluorocarbons or hydrofluorocarbons such as Chlorodifluoromethane, Trifluoromonofluoroethane, Difluoroethane, Chlorodifluoroethane, Heptafluoropropane, Dimethyl ether; compressed gases such as nitrous oxide, nitrogen carbon dioxide or admixtures thereof. More preferably, propane, isobutane and/or butane in liquefied form are used as propellants. Most preferably, deodorized liquefied petroleum gas is used. The propellant(s) may be present in an amount ranging from 3-25 w/w % of the composition. Preferably, the propellant(s) are present in an amount ranging from 5-15 % w/w of the composition. Most preferably, liquefied petroleum gas is used in the range of 8-10 % w/w of the composition.

Buffering agent according to the present invention includes phosphates such as sodium phosphate, sodium dihydrogen phosphate, sodium dihydrogen phosphate dihydrate, disodium hydrogen phosphate, disodium hydrogen phosphate dodecahydrate, potassium phosphate, potassium dihydrogen phosphate and dipotassium hydrogen phosphate; boric acid and borates such as, sodium borate and potassium borate; citric acid and citrates such as sodium citrate, potassium citrate and disodium citrate; acetates such as sodium acetate and potassium acetate and carbonates such as sodium carbonate and sodium hydrogen carbonate. The said buffering agents can be used as pH modifiers or pH adjusting agents. Preferably, citric acid and potassium citrate are used. A buffering agent is used in the range of 0.05 to 0.5%, preferably 0.1% of the total composition.

Additionally, a vehicle is used for the preparation of alcohol free foam of the present invention. An aqueous vehicle such as water is preferred, where in water phase is present in amount from 20% to 95% by weight of the said pharmaceutical composition.

Antimicrobial agent according to present invention includes but not limited to imidazolidinyl urea, diazolidinyl urea; phenoxyethanol; sodium methyl paraben, methylparaben, ethylparaben, and propylparaben; potassium sorbate; sodium benzoate; sorbic acid; benzoic acid; formaldehyde; citric acid; sodium citrate; chlorine dioxide; quaternary ammonium compounds such as benzalkonium chloride, benzethonium chloride, cetrimide, dequalinium chloride, and cetylpyridinium chloride; mercurial agents such as phenylmercuric nitrate, phenylmercuric acetate, and thimerosal; piroctone olamine; vitis vinifera seed oil; and alcoholic agents, for example, chlorobutanol, dichlorobenzyl alcohol, phenylethyl alcohol and benzyl alcohol. Preferably, phenoxyethanol is used. An antimicrobial agent is used in the range of 0.1 to 1.5%, preferably 1 %. w/w of the total composition.

Compositions according to present invention may optionally further comprise one or more solubilizer, stabilizer, anti oxidants, coloring agents, fragrances and the like. Example and suitable amount of said optional excipient is known to a skilled person or as given in Handbook of pharmaceutical excipients (sixth edition, 2009).

The pharmaceutical composition prepared according to the present invention can be used topically for the treatment of dermatological diseases and diseases including plaque psoriasis, pruritic manifestations, inflammatory manifestations and the like.

The invention will be further illustrated by the following examples, however, without restricting the scope to these embodiments.
Example 1:
Sr. No Ingredients Example 1 (a) Example 1 (b) Example 1 (c)
% w/w % w/w % w/w
1 Clobetasol propionate 0.05 0.05 0.05
2 Hexylene glycol 12 12 12
3 Diethylene glycol monoethyl ether (Transcutol) 2 2 2
4 Glycerin 5 5 5
5 polyvinyl pyrrolidone K30 (PVP-K30) 2 2 2
6 Polysorbate 60 0.6 0.6 0.6
7 Ceteareth-20 5 3.6 2.4
8 Citric acid anhydrous 0.02 0.02 0.02
9 Potassium citrate 0.08 0.08 0.08
10 Phenoxyethanol 1.0 1.0 1.0
11 Purified water 72.25 73.65 74.85
Total 100.0 100.0 100.0
12 Deodorized Liquefied Petroleum Gas (LPG) Propellant 10 10 10

(a) An aqueous phase was prepared by dissolving polyvinyl pyrrolidone in purified water and then adding glycerin, citric acid, potassium citrate at about 45°C till the solution appears clear.
(b) Clobetasol propionate was dissolved in hexylene glycol and then Ceteraeth-20, diethylene glycol monoethyl ether (Transcutol), Polysorbate 60 and phenoxyethanol were dissolved into the solution at 45°C to obtain a clear solution.
(c) Solution as prepared in step (a) was added slowly to solution prepared in step (b) and stirred at 45°C to ensure complete mixing
(d) The solution was filled into aluminum cans at 30°C and propellant is filled in cans at 25°C to obtain final foamable composition of Clobetasol Propionate.

The prepared foam compositions were evaluated for their physical appearance after dispensing and foam stability based on its breaking time at high temperature 40°C. The results are as reported in Table 1.

Table 1: Evaluation of foam composition prepared according to Example 1.
Quality attributes Example 1 (a) Example 1 (b) Example 1 (c)
Physical appearance of foam after dispensing White, fine, creamy and easily breaks on slight shear
Breaking time at about 40°C (Minutes) 5.75 3.50 3.10

It was observed that physically elegant and stable foam was produced after dispensing in case of all the examples 1(a), (b), (c). Also, the foam was thermostable for atleast 3 minutes even at high temperature at about 40°C. The foam prepared according to example 1(a) with ratio of Polysorbate 60 to Ceteareth-20 about 1:8 was found to be stable for more than 5 minutes at high temperature at about 40°C.

Example 2:
Sr. No Ingredients % w/w
1 Clobetasol propionate 0.05
2 Hexylene glycol 8
3 Cetyl alcohol 0.2
4 Glycerin 10
5 Polyvinyl pyrrolidone K30 (PVP-K30) 2
6 Polysorbate 60 0.6
7 Ceteareth-20 5
8 Citric acid anhydrous 0.02
9 Potassium citrate 0.08
10 Phenoxyethanol 1.0
11 Purified water q.s
Total 100.0
12 Deodorized Liquefied Petroleum Gas (LPG) Propellant 8

Composition of example 2 was prepared by following the process analogous to Example 1.