DESC:BACKGROUND OF THE INVENTION
Most of the topical diseases or disorders are caused by bacterial, fungal and viral infection. The most common topical diseases or disorders include eczema, psoriasis and dermatitis, including contact dermatitis, atopic dermatitis and seborrheic dermatitis. Dermatitis results from inflammatory processes that involve the upper dermis and epidermis of the skin.

Infections are caused by fungal, viral and microbial agents. Infections are treated systematically or topically by applying or using active agents in the form of creams, emulsion, lotion, gels or ointments. Most commonly used active agents are antibiotic agents, antifungal agents, steroidal agents and antibacterial agents.

Topical corticosteroids are widely used to treat inflammatory skin diseases. Topical corticosteroids are recommended first line therapy in dermatitis. Inappropriate use may be related to adverse effects such as skin atrophy or suppression of the Hypothalamic Pituitary Axis (HPA). Corticosteroid derivatives and formulations have been developed in the last decades with the aim of increasing efficacy and decreasing the incidence of adverse effects. More recently, however, the interest is more focused on improving the vehicles to fulfill patient’s preference in order to improve adherence. Adherence to topical therapy is an important issue, particularly in chronic skin diseases.

Different topical steroids have different potency ranging from mild to very potent topical steroids. Mometasone Furoate is used as a topical steroidal anti-inflammatory agent and used for inflammatory skin diseases such as the treatment of psoriasis (psoriasis) as well as various forms of dermatitis such as allergic contact dermatitis, chronic hand eczema or atopic eczema and other skin rashes.

Like other corticosteroids, mometasone furoate possesses anti-inflammatory, antipruritic, and vasoconstrictive properties. Mometasone Furoate has chemical name 9a,21-dichloro-11ß,17-dihydroxy-16a-methylpregna-1,4-diene-3,20-dione 17-(2-furoate) and has structural formula I:

Formula I: Mometasone furoate

Mometasone is a moderately potent topical steroid and often the first line and most commonly prescribed in dermatitis. Mometasone has good efficacy, minimal systemic penetration and good tolerability profile. Mometasone furoate is not soluble in water, has a low solubility in octanol and is sparingly soluble in ethyl alcohol. A suitable solvent for mometasone furoate is propylene glycol.

The poor solubility of mometasone furoate has deferred the development of efficacious, economic and stable topical formulation. Most challenging task for formulator is to incorporate poorly water-soluble drugs into effective products. Improving the solubility of the poorly soluble drug is considered to improve the bioavailability of the drug. Therefore, formulations where the active substance is in a dissolved state are generally preferred. Currently, a preparation with mometasone furoate with an increased amount of water in which the active ingredient is released is commercially available in the market under the brand name Ecural®.

Several examples of formulations comprising active ingredient either mono therapy or in combination are described below.

US patent number 8,728,497 discloses pharmaceutical compositions of mometasone or derivate thereof in the form of an oil-in-water emulsion, notably a cream.
US publication number 20120128736 discloses compositions of mometasone or a pharmaceutically acceptable derivate thereof in the form of an oil-in-water emulsion, notably a cream.

US patent number 4,808,610 discloses topical pharmaceutical composition of mometasone for the treatment of inflammation, wherein the composition is in the form of water-in-oil (w/o) emulsion.

US patent number 7,312,207 discloses a topical water-in-oil pharmaceutical cream composition of mometasone furoate for the treatment of inflammation.

The prior arts teach various pharmaceutical compositions of mometasone in the form of oil-in-water (o/w) emulsion for topical application and process of preparing such composition, but there exist a need to develop alternative formulation having excellent storage stability with maximum efficacy and good patient compliance in skin infections or dermatitis.

The inventors of the invention have found that it is possible to develop composition comprising mometasone or a salt thereof with suitable pharmaceutically acceptable excipients having excellent storage stability which provides good patient compliance. This invention provides stable pharmaceutical composition for topical use in to subject. The said composition is developed with 30% to 50% w/w water content of the composition in order to broaden the clinical spectrum of mometasone use and its adherence.

SUMMARY OF THE INVENTION
The invention provides pharmaceutical composition comprising mometasone or a salt thereof with suitable pharmaceutically acceptable excipients in the form of oil-in-water (o/w) emulsion. The said composition provides excellent storage stability and used in the treatment of inflammatory skin disease. The said composition comprises from about 30% to about 50% w/w water and provides better patient compliance. Further, the invention also provides process for preparing pharmaceutical composition mometasone or a salt thereof.

In one general aspect, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients in the form of emulsion.

In another general aspect, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein mometasone present in the form of fine particles, preferably in micronized form.

In another general aspect, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients in the form of oil-in-water (o/w) emulsion.

In another general aspect, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein the composition comprises amount of water present in the range from about 30% to about 50% w/w of the total weight of composition.

In another general aspect, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein the mometasone or a salt thereof is present in the range from about 0.08 % w/w to about 0.15% w/w of the composition.

In another general aspect, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein the excipients comprises co-surfactant present in the range from about 4.0% w/w to about 9.0% w/w of the composition and amount of surfactant present in the range from about 20% w/w to about 29% w/w of the composition, and said co-surfactant comprises caprylic/capric triglyceride.

In another aspect, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein the excipients comprises humectant and amount of humectant present in the range from about 5% w/w to about 25% w/w of the composition.

In another general aspect, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein the excipient contains one or more preservatives, which includes methyl paraben and propyl paraben.

In another general aspect, there is provided a stable pharmaceutical composition comprising:
(a) mometasone or a salt thereof,
(b) caprylic/capric triglyceride,
(c) propylene glycol or polyethylene glycol,
(d) macrogol 15 hydroxystearate and one or more suitable pharmaceutically acceptable excipients.

In another aspect, a stable pharmaceutical composition in the form of an oil-in-water emulsion for topical administration comprising:
a) from about 0.08% to about 0.15 % w/w of micronized mometasone or a salt thereof,
b) from about 20.0% to about 29.0 % w/w of macrogol 15 hydroxystearate,
c) from about 12.0% to about 20.0 % w/w of medium chain triglyceride, and
d) purified water to constitute 100% w/w.

In another general aspect, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof, wherein the average particle size of micronized mometasone or a salt thereof is less than 50µm, particularly 100% particle of micronized mometasone or a salt thereof are less than 50µm in size.

In another general aspect, there is provided a stable pharmaceutical composition in the form of an oil-in-water emulsion for topical administration comprising:
a) from about 0.08% to about 0.15% w/w of mometasone furoate,
b) from about 4.0% to about 9.0% w/w of caprylic/capric triglyceride,
c) from about 20.0% to about 29.0% w/w of macrogol 15 hydroxystearate,
d) from about 12.0% to about 20.0% w/w of medium chain triglyceride,
e) from about 5.0% to about 25.0% w/w of propylene glycol,
f) from about 0.20% to about 0.30% w/w of citric acid,
g) from about 0.22% to about 0.32% w/w of sodium citrate,
h) from about 0.07% to about 0.12% w/w of methyl paraben,
i) from about 0.008% to about 0.013% w/w of propyl paraben, and
j) purified water to constitute 100% w/w;
wherein the composition provides polydispersity index of the globules in the range of about 0.10 to about 0.2.

In another general aspect, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein the pH of the composition provides in the range of about 4 to about 6.

In another general aspect, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein the wherein the composition retains at least 90% w/w of the potency of mometasone or a salt thereof after 6 months when stored at 40° C and 75% relative humidity.

In another general aspect, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein the composition provides dosage form for topical application such as creams, emulsion, ointments, gels, lotions, foams, powders, shampoos, liquid solutions.

In another general aspect, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein the composition having density in the range from about 0.90 to about 1.03.

In another general aspect, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein the excipients are selected from group of surfactant, co-surfactant, emollients, viscosity modifying agent, humectants, stiffening agent, antioxidant, buffering agent, preservative, soothening agent, pH regulator or modifier, emulsifiers or mixture thereof and suitable solvent or vehicle.

In another general aspect, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein the invention provides dosage form for topical application in the form of emulsion and composition is stable after 6 months when stored at 40°C and 75% relative humidity or 25°C and 60 % relative humidity.

In another general aspect, there is provided a process for preparing stable pharmaceutical composition comprising mometasone or pharmaceutically acceptable salt thereof and suitable pharmaceutically acceptable excipients; wherein process comprises:
a) preparation of aqueous phase,
b) preparation of oil phase,
c) preparing solution of mometasone or pharmaceutically acceptable salt thereof, and
d) mixing of oil phase obtained in step (b) in to aqueous phase obtained in step (a) to get o/w emulsion.

In another general aspect, there is provided a process for preparing stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients; wherein process comprises:
a) preparation of aqueous phase,
b) preparation of oil phase,
c) preparing solution of mometasone or a salt thereof, and
d) mixing of oil phase obtained in step (b) in to aqueous phase obtained in step (a) to get emulsion;
wherein the aqueous phase comprises citric acid and sodium citrate; and the oil phase comprises propylene glycol or polyethylene glycol.

In another general aspect, there is provided a process for preparing stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients; wherein process comprises:
a) preparation of aqueous phase,
b) preparation of oil phase,
c) preparing solution of mometasone or a salt thereof,
d) mixing of oil phase obtained in step (b) in to aqueous phase obtained in step (a) to get emulsion; notably in the form of cream, and
e) mixing of emulsion obtained in step (d) in to step (c);
wherein the aqueous phase comprises citric acid and sodium citrate; and the oil phase comprises propylene glycol or polyethylene glycol.

DETAILED DESCRIPTION OF THE INVENTION
The terms "active," "active ingredient or ingredients", “therapeutic agent” and “active agent” are used interchangeably and are meant to refer to a substance intended to be delivered, capable of imparting a desired action or effect. Such substances include, but are not limited to, pharmaceuticals, medicaments, drugs, therapeutic agents, diagnostic agents, cosmetic agents, nutritional supplements and mixtures thereof. More specifically, without limiting the scope of the invention, such substances include pain relievers, cough and cold ingredients, anti-inflammatory, analgesic, antipyretic, anticholinergic or antispasmodics, antibiotics, sedatives, antifungal, steroid, stimulants, antihistamines, antiallergenic, diuretics, expectorants, hormones, antipsychotics, narcotics and mixtures thereof. Specifically such active agent comprises mometasone furoate.

The term "pharmaceutically acceptable excipients" includes a pharmaceutically acceptable material, vehicle, suitable for administering or applying an active pharmaceutical ingredient. Each excipient should be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient.

The term "mometasone " as used herein refers to mometasone base or its salts, solvates, prodrugs, hydrates, enantiomers or polymorphs thereof, more specifically mometasone is refers to mometasone furoate.

The term “co-surfactant” as used herein refers to any substance or chemical added to a process to enhance the effectiveness of a surfactant.

The term "subject" refers to an animal, preferably a mammal, and most preferably a human, who is the object of treatment, observation or experiment.

The term “pharmaceutically acceptable salt” or “salt” as used herein refers to salts which are known to be non-toxic and are commonly used in the pharmaceutical literature. Such pharmaceutically acceptable salts thus includes but are not limited to furoate, acetate, hydrochloride salt, phenylacetate, trifluoroacetate, acrylate, ascorbate, benzoate, chlorobenzoate, dinitrobenzoate, hydroxybenzoate, phenylbutyrate, beta-hydroxybutyrate, chloride, cinnamate, citrate, formate, fumarate, glycolate, heptanoate, lactate, maleate, hydroxymaleate, malonate, mesylate, nitrate, oxalate, phthalate, phosphate, monohydro phenylpropionate, salicylate, bisulfate, pyrosulfate, sulfite, bisulfite, sulfonate, ethanesulfonate, 2-hydroxyethanesulfonate, xylenesulfonate, tartarate, and the like.

The term "stable" means the quantitative composition does not significantly change over the time, during the entire shelf-life of the composition for at least 3 months, advantageously for at least 6 months, more advantageously for at least 9 months.

The term "potency" relates to the amount of efficacious component. Typically, as used herein, it refers to the efficacious amount of a given component at a given time in comparison to the efficacious amount of the same component at a second time. Typically, potency is expressed as a percentage. For example, a 10% reduction in potency of component A after three months means that the efficacious amount of component A present after a three month period is 90% of the original efficacious amount of component A.

In one embodiment, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients in the form of oil-in-water emulsion.

In another embodiment, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein mometasone present in the form of fine particles, notably in micronized form.

In another embodiment, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof, wherein the particle size of micronized mometasone or a salt thereof is less than 50 µm.

In another embodiment, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein the composition comprises amount of water present in the range from about 30% to about 50% w/w of the composition.

In an embodiment, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients in the form of oil in water emulsion.

In another embodiment, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein the mometasone is present in the range from about 0.08 % w/w to about 0.15% w/w, particularly 0.1% of the composition.

In another embodiment, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein the excipients comprises co-surfactant and amount of co-surfactant present in the range from about 4.0% w/w to 9.0 % w/w of the composition, preferably from about 5% w/w to about 7% w/w of the composition, and more preferably about 6% w/w of the composition.

In another embodiment, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein the suitable excipients comprises co-surfactant, whereas the co-surfactant used in the composition is caprylic/capric triglyceride.

In another embodiment, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein the excipients comprises surfactant and amount of surfactant present in the range from about 20% w/w to about 29% w/w of the composition, preferably from about 21% w/w to about 26% w/w of the composition, and more preferably about 24% w/w of the composition.

In another embodiment, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein the suitable excipients comprises surfactant, whereas the surfactant used in the composition is Macrogol 15 hydroxystearate.

In another embodiment, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein the excipients comprises humectant and amount of humectant present in the range from about 5% w/w to about 25% w/w of the composition, preferably in the range of 14% w/w to 21% w/w of the composition, more preferably about 17.2 % w/w of the composition.

In another embodiment, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein the suitable humectant used in the composition is propylene glycol or polyethylene glycol.

In another embodiment, there is provided a stable pharmaceutical composition comprising:
(a) mometasone or a salt thereof,
(b) caprylic/capric triglyceride, and
(c) propylene glycol or polyethylene glycol and one or more suitable pharmaceutically acceptable excipients.

In another embodiment, there is provided a stable pharmaceutical composition comprising:
(a) mometasone or a salt thereof,
(b) caprylic/capric triglyceride,
(c) propylene glycol or polyethylene glycol,
(d) macrogol 15 hydroxystearate and one or more suitable pharmaceutically acceptable excipients; wherein the composition is provides in the form of o/w emulsion.

In another embodiment, a stable pharmaceutical composition in the form of an oil-in-water emulsion for topical administration comprising:
a) from about 0.08% to about 0.15 % w/w of micronized mometasone or a salt thereof,
b) from about 20.0% to about 29.0 % w/w of macrogol 15 hydroxystearate,
c) from about 12.0% to about 20.0 % w/w of medium chain triglyceride, and
d) purified water to constitute 100% w/w,
wherein the particle size of micronized mometasone or a salt thereof is less than 50 µm.

In another embodiment, there is provided a stable pharmaceutical composition in the form of an oil-in-water emulsion for topical administration comprising:
a) from about 0.08% to about 0.15% w/w of mometasone furoate,
b) from about 4.0% to about 9.0% w/w of caprylic/ capric triglyceride,
c) from about 20.0% to about 29.0% w/w of macrogol 15 hydroxystearate,
d) from about 12.0% to about 20.0% w/w of medium chain triglyceride,
e) from about 5.0% to about 25.0% w/w of propylene glycol,
f) from about 0.20% to about 0.30% w/w of citric acid,
g) from about 0.22% to about 0.32% w/w of sodium citrate,
h) from about 0.07% to about 0.12% w/w of methyl paraben,
i) from about 0.008% to about 0.013% w/w of propyl paraben, and
j) purified water to constitute 100% w/w; wherein the composition is provides in the form of o/w emulsion.

In another embodiment, there is provided a stable pharmaceutical composition in the form of an oil-in-water emulsion for topical administration comprising:
a) about 0.1 % w/w of Mometasone furoate,
b) about 6 % w/w of caprylic/ capric triglyceride,
c) about 24 % w/w of Macrogol 15 hydroxystearate,
d) about 16 % w/w of Medium chain triglyceride,
e) about 17.2 % w/w of Propylene glycol,
f) about 0.25% w/w of Citric acid,
g) about 0.27 % w/w of Sodium citrate,
h) about 0.1 % w/w of Methyl paraben,
i) about 0.01 % w/w of Propyl paraben, and
j) purified water to constitute 100% w/w of composition; wherein the composition is provides in the form of o/w emulsion.

In another embodiment, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein the composition provides pH in the range of about 4 to about 6.

In another embodiment, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein the excipients comprises one or more preservatives, said preservative comprises methyl paraben, propyl paraben or mixture threrof.

In another embodiment, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein the composition provides dosage form for topical application such as creams, emulsion, ointments, gels, emulsion, lotions, foams, powders, shampoos, liquid solutions.

In another embodiment, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein the excipients are selected from group of surfactant, co-surfactant, emollients, viscosity modifying agent, humectants, stiffening agent, antioxidant, buffering agent, preservative, soothening agent, pH regulator or modifier, emulsifiers or mixture thereof and suitable solvent or vehicle.

In another embodiment, there is provided a stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein the invention provides dosage form for topical application in the form of emulsion.

In another embodiment, there is provided a pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients, wherein the composition is stable for more than 6 months when stored at 40°C and 75% relative humidity or 25°C and 60 % relative humidity (RH).

In another embodiment, there is provided a process for preparing stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients; wherein process comprises:
a) preparation of aqueous phase,
b) preparation of oil phase,
c) preparing solution of mometasone or a salt thereof, and
d) mixing of oil phase obtained in step (b) in to aqueous phase obtained in step (a) to get emulsion,

In another embodiment, there is provided a process for preparing stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients; wherein process comprises:
a) preparation of aqueous phase,
b) preparation of oil phase,
c) preparing solution of mometasone or a salt thereof, and
d) mixing of oil phase obtained in step (b) in to aqueous phase obtained in step (a) to get emulsion;
wherein the preparation aqueous phase comprises dissolution of citric acid and sodium citrate in purified water; and the preparation of oil phase comprises heating of propylene glycol and further mixing of methyl paraben and propyl paraben to heated propylene glycol.

In another embodiment, there is provided a process for preparing stable pharmaceutical composition comprising mometasone or a salt thereof and suitable pharmaceutically acceptable excipients; wherein process comprises:
a) preparation of aqueous phase,
b) preparation of oil phase,
c) preparing solution of mometasone or a salt thereof, and
d) mixing of oil phase obtained in step (b) in to aqueous phase obtained in step (a) to get o/w emulsion, notably cream.
e) mixing of the emulsion obtained in (d) in to step (c);
wherein the preparation aqueous phase comprises dissolution of citric acid and sodium citrate in purified water; and the preparation of oil phase comprises heating of propylene glycol and further mixing of methyl paraben and propyl paraben to heated propylene glycol.

Examples of humectants used in the composition of invention are selected from group comprises but are not limited to glycerin and sorbitol; and emulsifiers may be glyceryl monostearate, propylene glycol, glyceryl monoleate, polyoxyethylene cetyl ether, polyoxyethylene cetostearyl ether, polyoxyethylene stearyl ether, and polyethylene glycol stearate or mixture thereof.

Examples of preservative used in the composition of invention are selected from group comprises but are not limited to methyl paraben, propyl paraben, chlorocresol, potassium sorbate, benzoic acid and the like, or any combination thereof.

Examples of buffering agent used in the composition of invention are selected from group comprises but are not limited to barium hydroxide, calcium hydroxide, citric acid, sodium citrate, sodium bicarbonate, sodium carbonate, sodium triphosphate, calcium carbonate, disodium monophosphate or mixture thereof.

Examples of surfactant used in the composition of present are selected from group comprises but are not limited to macrogol 15 hydroxystearate, cationic surfactants, anionic surfactants such as linear alkylbenzene sulfonates, di-alkyl sulfosuccinate (sulfonic acid salt), sodium lauryl sulfate (alcohol sulfate), phosphoric acid esters, sodium stearate (carboxylic acid salt); non-ionic surfactants: alkylphenol ethoxylates, alcohol ethoxylates, alkanolamides; amphoteric surfactants: sodium lauriminodipropionate and disodium lauroamphodiacetate and polysorbate or mixture thereof.

Examples of co-surfactant used in the composition of invention are selected from group comprises but are not limited to Methanol, caprylic/ capric triglyceride, 1-butanol, tertiary butyl alcohol, ethanol, medium chain alcohols (5-8 carbon units).

Vehicle is a substance that can chemically different liquid, solid or gas. Examples of solvent suitable for use in oral pharmaceutical composition are selected from group comprises but not limited to purified water, isopropyl alcohol, dichloromethane, glycerol, propylene glycol, ethanol, chlordiazepoxide hydrochloride or mixture thereof.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

The invention is further illustrated by the following examples which are provided merely to be exemplary of the invention and do not limit the scope of the invention. Certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the invention.

The invention now will be described in particularity with the following illustrative example; however, the scope of the present invention is not intended to be, and shall not be, limited to the exemplified embodiments below.

EXAMPLES
Example 1: Pharmaceutical composition of mometasone or a salt thereof.
Table 1
Sr. No. Ingredient Quantity (%w/w)
1. Mometasone furoate 0.08-0.15
2. caprylic/capric triglyceride 4.0-9.0
3. Macrogol 15 hydroxystearate 20-29
4. Medium chain triglyceride 12-20
5. Propylene glycol 5-25
6. Citric acid 0.20-0.30
7. Sodium citrate 0.22-0.32
8. Methyl paraben 0.07-0.12
9. Propyl paraben 0.008-0.013
10. Purified water 25-55 (Q.S. to 100%)
Total 100

Process:

1. Transferred macrogol 15 hydroxystearate in a stainless still container and melted by heating at 40° C,
2. Added mometasone and dissolved it under stirring and cool it to 30° C,
3. Caprylic/capric triglyceride and medium chain triglyceride were added in step 2 and mixed,
4. Simultaneously, sodium citrate and citric acid were added in purified water and mixed to form clear solution and add slowly into step 3,
5. Propylene glycol was heated to about 50° C to about 55° C in separate container,
6. Methyl paraben and propyl paraben were added in to step 5 and dissolved,
7. Sodium citrate and citric acid were added into required quantity of purified water, checked the clarity of the solution and further added in to the material obtained by step 3 under sterring,
8. Mix the step 6 material with step 4 material under stirring,
9. Finally stirred the bulk emulsion for about 10 minutes,
10. Maintained the pH of formulation to about 4 to about 6.

Example 2: Pharmaceutical composition of mometasone or a salt thereof.
Table 2
Sr. No. Ingredient Quantity (%w/w)
1. Mometasone furoate 0.10
2. caprylic/capric triglyceride 6.0
3. Macrogol 15 hydroxystearate 24.0
4. Medium chain triglyceride 16.0
5. Polyethylene glycol 17.27
6. Citric acid 0.25
7. Sodium citrate 0.27
8. Methyl paraben 0.10
9. Propyl paraben 0.01
10. Purified water 36.0
Total 100

Process: Same as described in the example 1.

Stability data:
Table 3
Initial 6 Months
40°C and 75 % RH 25°C and 60 % RH
Description White colour translucent emulsion White colour translucent emulsion White colour translucent emulsion
Density 1.018 1.0215 1.0225
pH 5 5.08 5.1
Assay 93.7 95 95

,CLAIMS:1. A stable pharmaceutical composition for topical administration in the form of an oil-in-water emulsion comprising:
a) from about 0.08% to about 0.15% w/w of micronized mometasone or a salt thereof,
b) from about 20.0% to about 29.0 % w/w of macrogol 15 hydroxystearate,
c) from about 12.0% to about 20.0 % w/w of medium chain triglyceride, and
d) water to constitute 100% w/w,
wherein the particle size of micronized mometasone or a salt thereof is less than 50 µm.

2. The stable pharmaceutical composition according to claim 1, wherein the composition further contains propylene glycol in an amount ranging from about 5% w/w to about 25% w/w of the composition.

3. The stable pharmaceutical composition according to claim 1, wherein the composition further contains caprylic/ capric triglyceride in an amount ranging from about 4.0% to about 9.0% w/w of the composition.

4. The stable pharmaceutical composition according to claim 1, wherein density of the composition is in the range of about 0.90 to about 1.03.

5. A stable pharmaceutical composition in the form of an oil-in-water emulsion for topical administration comprising:
a) from about 0.08% to about 0.15% w/w of mometasone furoate,
b) from about 4.0% to about 9.0% w/w of caprylic/ capric triglyceride,
c) from about 20.0% to about 29.0% w/w of macrogol 15 hydroxystearate,
d) from about 12.0% to about 20.0% w/w of medium chain triglyceride,
e) from about 5.0% to about 25.0% w/w of propylene glycol,
f) from about 0.20% to about 0.30% w/w of citric acid,
g) from about 0.22% to about 0.32% w/w of sodium citrate,
h) from about 0.07% to about 0.12% w/w of methyl paraben,
i) from about 0.008% to about 0.013% w/w of propyl paraben, and
j) purified water to constitute 100% w/w.

6. The stable pharmaceutical composition according to claim 1, 5 or 6, wherein the globule size of an emulsion ranges from about 30 µm to about 700µm.

7. The stable pharmaceutical composition according to claim 1, 5 or 6, wherein the polydispersity index of the globules is about 0.10 to about 0.2.

8. The stable pharmaceutical composition according to claim 1, wherein the pharmaceutically acceptable salt is furoate.

9. The stable pharmaceutical composition according to claim 1, wherein pH of the composition is in the range of 4 to 6.

10. The stable pharmaceutical composition according to any of the preceding claim, wherein the composition retains at least 90% w/w of the potency of mometasone or a salt thereof after 6 months when stored at 40°C and 75% relative humidity.