WO2020100096A1

WO2020100096A1 - Topical composition comprising mupirocin

Info

Publication number: WO2020100096A1
Application number: PCT/IB2019/059822
Authority: WO
Inventors: Sushrut Kulkarni; Ulhas Dhuppad; Madhusudhan BOMMAGANI; Ram Reddy PATLOLLA; Atul Chopade; Vivek Ramdas ALAI; Bikash Kumar PATRO; Ambar BONGIRWAR; Nitin Babulal Bhamre
Original assignee: Glenmark Specialty S.A.
Priority date: 2018-11-15
Filing date: 2019-11-15
Publication date: 2020-05-22

Abstract

The present invention relates to a topical composition comprising mupirocin or a pharmaceutically acceptable salt(s) thereof and it also relates to a stable, film-forming, compositions comprising mupirocin or a pharmaceutically acceptable salt(s). Further, the present invention relates to a process of preparing such compositions, and methods of using such compositions.

Description

TOPICAL COMPOSITION COMPRISING MUPIROCIN

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the priority benefit of Indian provisional application serial number Nos. 201821043019 filed on November 15, 2018, and 201921036002 filed on September 06, 2019.

FIELD OF THE INVENTION

BACKGROUND

The skin disorders are preferably treated locally by topically administering active agent(s) via various topical dosage forms like cream, gel, ointment and like. In the case of treating infective skin disorder(s), there are numerous treatments, both topical and systemic, are available for the primary and secondary skin infection caused by sensitive Gram-positive organisms such as Staphylococcus aureus, Streptococcus spp, etc.

Topical and systemic bacterial infection treatment compositions typically employ at least one active pharmaceutical ingredient (API) in combination with a base component. In the cream form, the APIs typically comprise an antibiotic/antibacterial such as mupirocin, ketoconazole and the like. Mupirocin is one the examples of an antibiotic/antibacterial agent.

Mupirocin or pseudomonic acid A is an antibiotic agent produced by fermentation of Pseudomonas fluorescens. Mupirocin is active against a wide range of gram-positive and certain gram-negative bacteria by the inhibition of bacterial protein synthesis by reversibly and specifically binding to bacterial isoleucyl transfer-RNA synthetase. Mupirocin is represented by structural formula (I)

Formula (I)

Mupirocin is indicated for primary bacterial skin infections including impetigo and folliculitis and secondary bacterial skin infections such as dermatitis.

Mupirocin is currently marketed by Smithkline Beecham in the pharmaceutical form of an ointment, a cream, and a nasal ointment under the tradename of BACTROBAN®. BACTROBAN® is applied thrice a day for at least 10 days using a cotton gauze. BACROBAN® contains polyethylene glycol that can be absorbed through open wounds and may cause skin damage.

Secondary bacterial infection in skin lesions is a common problem. Bacterial infections occur frequently in lesions of eczema and atopic dermatitis. Secondary bacterial skin infections are common complications of primary dermatoses, primary nonbacterial skin infections, traumatic lesions, ulcers, cutaneous infestations, and other miscellaneous skin diseases. Secondarily infected traumatic skin lesions are but not limited to a laceration, sutured wound, or abrasion.

Impetigo is a highly contagious, superficial skin infection that most commonly affects children two to five years of age. The most common presentation is yellowish crusts on the face, arms, or legs. Less commonly there may be large blisters that affect the groin or armpits. The lesions may be painful or itchy. Red sores quickly rupture, ooze for a few days and then form a yellowish-brown crust. The sores usually occur around the nose and mouth but can be spread to other areas of the body by fingers, clothing, and towels. Itching and soreness are generally mild. A less common form of the disorder, called bullous impetigo, may feature larger blisters that occur on the trunk of infants and young children. A more serious form of impetigo, called ecthyma, penetrates deeper into the skin— causing painful fluid- or pus-filled sores that turn into deep ulcers. People are exposed to the bacteria that cause impetigo when they come into contact with the sores of someone who's infected or with items they've touched— such as clothing, bed linen, towels, and even toys. It is a highly contagious skin infection that mainly affects infants and children.

There is no standard treatment for impetigo, the topical antibiotics mupirocin, and fusidic acid are effective and may be superior to oral antibiotics. Oral antibiotics should be considered for patients with extensive disease. Oral penicillin V is seldom effective; otherwise, there is no clear preference among antistaphylococcal penicillins, amoxicillin/clavulanate, cephalosporins, and macrolides, although resistance rates to erythromycin are rising.

International patent application publication no. 2012/052472 discloses anhydrous topical gel formulation of mupirocin comprising a lipophilic base from petroleum, medium-chain triglycerides and their mixtures, a bioadhesive agent from polyvinylpyrrolidone and polymethacrylates.

United States Patent Application Publication number 2012/0108527 relates to a film forming topical pharmaceutical composition comprising mupirocin and polyvinylpyrrolidone/vinyl acetate copolymer.

International patent application publication no. 2008/007182 relates to a stable topical pharmaceutical composition comprising mupirocin, and (b) one or more esters of a fatty acid which is substantially free of fatty alcohols.

European patent number 0933081 relates to a pharmaceutical composition comprising mupirocin, in a carrier selected from oleyl alcohol, castor oil and a mixture thereof. United States Patent 4,524,075 claims several stable formulations of mupirocin containing polyethylene glycol as an inactive ingredient. United States Patent 6,025,389 discloses a pharmaceutical composition comprising a cream base which comprises mupirocin dihydrate, a mineral oil, one or more fatty alcohols or fatty esters, a polyoxyethylene ether or ester surfactant, xanthan gum, water.

United States Patent 4,524,075 assigned to Beecham describes topical composition comprising Mupirocin and a stabilizing amount of a poly (alkylene) glycol, or a poly (alkoxy substituted alkylene) glycol.

United States Patent 6,025,389 discloses a pharmaceutical or veterinary composition comprising a cream base and a therapeutic agent, such as mupirocin, and a method for treating a bacterial infection using the composition.

European patent number 0069423 discloses a composition called "fatty-creams" and the composition comprise from 50 to 80% by weight of fatty materials, 1.5 to 5% by weight of hydrophilic, and non-ionic surfactant.

European patent number 0251434 discloses inter alia various cream formulations containing the antibiotic mupirocin, liquid paraffin, water, emulsifier and the like..

Veluru Kinnera et al ( International Journal of Innovative Pharmaceutical Research. 2015,6(2), 478-484) discloses composition of mupirocin encapsulated sodium alginate microspheres.

V. Shanmugam et al, ( Asian Journal of Pharmaceutics ; Jul-Sep 2016 (Suppl) · 10 (3) 5320), discloses composition and in vitro evaluation of mupirocin-loaded alginate microspheres.

CN105999362A and CN105903056 relate to alginate dressing impregnated with the antibacterial drug.

There is a need for a stable topical composition comprising mupirocin that provides bio-adhesive, occlusive property for the healing of the wound. With the use of alginate dressing, there is a risk of dehydrating wound bed and delaying wound healing (risk of scab formation). The absorptive dressing has a limitation of lack of activity from mupirocin in wound exudate and moist environment. Hence, there is a need for an improved formulation of mupirocin for the treatment of skin infective disorders.

SUMMARY OF THE INVENTION

The present invention relates to a topical composition comprising mupirocin or a pharmaceutically acceptable salt(s) thereof.

In an aspect, the present invention relates to a topical composition comprising mupirocin or a pharmaceutically acceptable salt(s) thereof; a polymeric substance(s); and one or more pharmaceutically acceptable excipient(s) thereof.

In another aspect, the present invention relates to topical composition comprising mupirocin or a pharmaceutically acceptable salt(s); a polymeric substance(s) selected from a group consisting of polymeric substance; an oil component; wherein the composition comprises oil component(s) from about 10% w/w to about 98% w/w.

In one of the aspect, the polymeric substance is pH independent polymer.

In one of the aspect, the polymeric substance is non-ionic pH independent polymer.

In some aspects, the oil component is selected from mineral oil, isopropyl myristate, petrolatum, medium-chain triglyceride, fatty acid, esters of fatty acid, fatty alcohol, ethers of fatty alcohol and combinations thereof.

In some aspects, the polymeric substance is selected from a group consisting of copolymer of ethyl acrylate, methyl ethacrylate and a copolymer of ethyl acrylate, methyl methacrylate and a low content of methacrylic acid ester with quaternary ammonium groups, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, ethylcellulose, cellulose acetate butyrate, cellulose acetate, alginate, chitosan, and xanthan gum.

In some aspects, the non-ionic pH-independent polymer is hydroxypropyl cellulose. In some aspects, the polymeric substance is chitosan.

In some aspects, the polymeric substance is alginate.

In some aspects, the topical composition comprising water from about 0% w/w to about 50% w/w based on the total weight of the composition.

In some aspects, the mupirocin is completely solubilized in the composition.

In some aspects, the mupirocin is solubilized in a vehicle and the vehicle is selected from lower alcohol(s), glycol(s) or it's derivative(s), dimethyl isosorbide, dimethyl sulfoxide, glycofurol, water and any combinations thereof.

In some aspects, the mupirocin is solubilized in a vehicle and the vehicle is selected from ethanol, isopropyl alcohol, propanol, butanol, pentanol, hexanol, ethylene glycol, propylene glycol, polyethylene glycol, butylene glycol, pentylene glycol, hexylene glycol, diethylene glycol monoethyl ether, dimethyl isosorbide, dimethyl sulfoxide, glycofurol, water and any combinations thereof.

In a specific aspect, the vehicle for mupirocin is selected from ethanol, isopropyl alcohol, propylene glycol, polyethylene glycol, hexylene glycol, diethylene glycol monoethyl ether, dimethyl isosorbide, dimethyl sulfoxide, glycofurol, water and any combinations thereof.

In some aspects, the mupirocin is partially solubilized in the composition.

In some aspects, the mupirocin is dispersed in the composition.

In some aspects, the mupirocin is dispersed in a vehicle, and the vehicle is selected from oil-in-water emulsion, water-in-oil emulsion, oil-in-glycol emulsion, glycol-in- oil emulsion, oil component(s), mixture of water-miscible and water-immiscible substance(s) and any combinations thereof.

In some aspects, the mupirocin is present in the composition from about 0.1% w/w to about 5% w/w based on the total weight of the composition. In a specific aspect, the mupirocin is present in the composition from about 1 % w/w to about 3% w/w based on the total weight of the composition.

In a specific aspect, the mupirocin is present in the composition is less than about 2% w/w based on the total weight of the composition or less than 2% w/w based on the total weight of the composition or less than about 1.75 w/w based on the total weight of the composition or less than about 1.5% w/w based on the total weight of the composition or less than about 1.25% w/w based on the total weight of the composition or less than about 1 % w/w based on the total weight of the composition.

In some aspects, the topical composition of the present invention is chemically and physically stable at ambient temperature for a period of at least one month.

In some aspects, the topical composition is spreadable.

In some aspects, the topical composition of the present invention is not microsphere formulation.

In some aspects, the topical composition is having at least one property selected from sustain release, film-forming composition, occlusive composition, and bio adhesiveness.

In some aspects, the topical composition of the present invention provides sustained release matrix upon administration at the application site.

In some aspects, the topical composition of the present invention further comprises a plasticizer selected from a group consisting of tributyl phosphate, trioctyl phosphate, trimethyl citrate, triethyl citrate and acetyl triethyl citrate, dioctyl adipate diethyl adipate, dimethyl phthalate, diethyl phthalate, diethyl sebacate, dipropyl sebacate, glycerol diacetate, glycerol triacetate (triacetin), glycerol monolactate diacetate, ethylene glycol diacetate, ethylene glycol dibutyrate, triethylene glycol diacetate, triethylene glycol dibutyrate and triethylene glycol dipropionate.

In another aspect, the present invention relates to a topical composition comprising mupirocin or a pharmaceutically acceptable salt(s), a polymeric substance and a plasticizer; wherein the plasticizer is present in an amount from about 0.01% to about 20% based on the total weight of the composition.

In a specific aspect, the topical composition comprising: i) mupirocin or a pharmaceutically acceptable salt(s) thereof; ii) from about 0.1% w/w to about 10% w/w of a polymeric substance; iii) from about 0% w/w to about 60% w/w of a penetration enhancer(s); iv) an oil component; and v) optionally purified water from 0% w/w to 50% w/w based on total weight of the composition; wherein the composition comprises oil component(s) from about 20% w/w to about 98% w/w. In a specific aspect, the topical composition comprises: i) from about 0.1 to about 5 % w/w of mupirocin or a pharmaceutically acceptable salt(s) thereof; ii) a polymeric substance comprises from about 0.1% w/w to about 10% w/w of hydroxypropyl cellulose; iii) a penetration enhancer comprises from about 0.1% w/w to about 50% w/w of oleic acid; iv) an emollient is selected from medium-chain triglyceride, isopropyl myristate, and cyclomethicone; v) from about 10% w/w to about 99% w/w of a vehicle; wherein the composition has bioadhesive property.

In a specific aspect, the topical composition comprising: i) mupirocin or a pharmaceutically acceptable salt(s) thereof; ii) from about 0.1% w/w to about 10% w/w of a polymeric substance(s) selected from copolymer of ethyl acrylate, methyl ethacrylate and a copolymer of ethyl acrylate, methyl methacrylate and a low content of methacrylic acid ester with quaternary ammonium groups, hydroxypropyl cellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, ethylcellulose, cellulose acetate butyrate, cellulose acetate, alginate, chitosan and xanthan gum; iii) from about 0% w/w to about 60% w/w of a penetration enhancer(s); iv) an oil component; and v) purified water from 0% w/w to about 50% w/w based on total weight of the composition; wherein the composition comprises oil component(s) from about 20% w/w to about 98% w/w. In a specific aspect, the present invention relates to a topical composition comprising: i) from about 0.1 to about 5 % w/w of mupirocin or a pharmaceutical acceptable salt(s) thereof; ii) about 1 to about 10 % w/w of sodium alginate; iii) about 0.5 to about 5% w/w of calcium chloride or suitable hydrate thereof; iv) about 0.5 to about 5% w/w of benzyl alcohol; v) about 0.5 to about 10% w/w of polyoxyl 20 cetostearyl ether, vi) about 1 to about 10% w/w of acrylamide / sodium acryloyldimethyltaurate copolymer / isohexadecane / polysorbate 80; vii) about 5 to about 50% w/w of a mineral oil; and viii) about 50 to about 95% w/w/ of purified water.

In an aspect, the present invention relates to a method of treating and/or preventing skin disorder in a subject; wherein the method comprises i. administering a topical composition comprising mupirocin or a pharmaceutically acceptable salt(s) to the skin area of a subject in need thereof.

Topical cream, gel, creamogel / emulgel, ointment, paste, unguent, emulsion (water- in-oil emulsion, oil-water-oil emulsion, water-oil-water emulsion, oil-in-water emulsion), liniment, paste, suspension, lotion foam formulations and the like according to the present invention, have been found that have good skin compatibility, promote wound healing, independently possess bactericidal activity and enhance the activity of anti-infective active agents. However, the present invention is not limited to creams, gel, and creamogel for topical application. Essentially any pharmaceutical carrier formulation suitable for topical application is within the scope of the present invention.

In some aspects, the skin disorder is selected from an infective skin disorder and non- infective skin disorder.

In some aspects, the skin disorder is an infected and/or non-infected wound.

In some aspects, the infective skin disorder(s) are selected from bacterial infection(s) and/or fungal infection(s).

In a specific aspect, the infective skin disorder is a bacterial infection that can be a primary skin infection or secondary skin infection.

In a specific aspect, the infective skin disorder is secondarily infected traumatic skin lesion.

In a specific aspect, the infective skin disorder is impetigo.

In some aspects, the non-infective skin disorder(s) are selected from dermatitis, skin rashes, toxic epidermal necrolysis.

In another aspect, the present invention relates to a method of preventing and/or treating an infective skin disorder in a subject; wherein the method comprises administering a topical composition comprising mupirocin or a pharmaceutically acceptable salt(s) onto the skin of the subject; wherein the method comprises administering the composition at least once daily at least for one day.

In an aspect, the present invention relates to a method of preventing and/or treating an infective skin disorder in a subject; wherein the method comprises administering a topical composition comprising mupirocin or a pharmaceutically acceptable salt(s) onto the skin of the subject; wherein the method comprises administering the composition at least once daily, at least for a week.

In a specific aspect, the present invention relates to a method of preventing and/or treating an infective skin disorder in a subject; wherein the method comprises administering a topical composition comprising mupirocin or a pharmaceutically acceptable salt(s) and an alginate onto the skin of the subject; wherein the method provides synergistic outcome.

In some aspects, the method comprises administering a sufficient quantity of the composition, based on the size of the lesion, onto the affected area forming a thin layer.

In another aspect, the present invention relates to a process of preparing topical composition comprising mupirocin; wherein the process comprises steps of: i) preparing mupirocin phase in the form of dispersion/solution; ii) preparing base composition; and iii) preparing final composition from the components of step i) and ii); wherein the base composition is selected from gel base or cream base, and the mupirocin phase is added to base composition either during preparing or after preparation.

In some aspects, the process of preparing comprises preparing the base composition; wherein the base composition is cream-based and is prepared by conventional techniques well known to those skilled in the art. Generally, a suitable process comprises admixing the various ingredients of the cream in appropriate relative amounts in any order that is convenient and thereafter, and if necessary, adjusting the pH to the final desired value. For example, the components of the base may be mixed together at room temperature or at an elevated temperature, for example, 35-40° C or 45-50° C or 50-55° C or 55-60° C or 60-70° C., until an emulsion has formed. The therapeutic agent may be added after cooling the emulsified cream base, or during mixing, if it is stable to the temperatures employed.

In some aspects, the process of preparing comprises preparing the base composition; wherein the base composition is gel base and is prepared by conventional techniques well known to those skilled in the art. Generally, a suitable process comprises admixing the various ingredients of the gel in appropriate relative amounts in any order that is convenient and thereafter, and if necessary, adjusting the pH to the final desired value. For example, the components of the base may be mixed together at room temperature or at an elevated temperature, for example, 35-40° C or 45-50° C or 50- 55° C or 55-60° C or 60-70° C, until a gel has formed. The therapeutic agent may be added after cooling the gel base, or during mixing, if it is stable to the temperatures employed.

DETAILED DESCRIPTION

Disclosed herein are detailed descriptions of specific aspects of the present invention of a topical mupirocin composition in the form of a cream, gel, emulgel, ointment, paste, unguent, emulsion (water-in-oil emulsion, oil-water-oil emulsion, water-oil- water emulsion, oil-water emulsion), liniment, paste, suspension, lotion and the like and foam. It will be understood that the disclosed embodiments are merely examples of the way in which certain aspects of the application can be implemented and do not represent an exhaustive list of all of the ways the application may be embodied.

The term“treatment” or“treating” of a state, disorder or condition as used herein means: (1) preventing or delaying or ameliorating or reducing or decreasing or the appearance of clinical symptoms of the state, disorder or condition developing in a mammal that may be afflicted with or predisposed to the state, disorder or condition but does not yet experience or display clinical or subclinical symptoms of the state, disorder or condition, (2) inhibiting the state, disorder or condition, i.e., arresting or reducing the development of the disease or at least one clinical or subclinical symptom thereof, or (3) improving or relieving the disease, i.e., causing regression of the state, disorder or condition or at least one of its clinical or subclinical symptoms. The benefit to a subject to be treated is either statistically significant or at least perceptible to the subject or to the physician.

The term“subject” as used herein refers to a human subject or an animal including mammals (such as domestic pets, for instance, cats and dogs) in the need of topical anti-infective treatment.

The term“about” has its usual meaning in the context of pharmaceutical formulations to allow for reasonable variations in amounts that can achieve the same effect. As used herein, the term“about” when used to refer to weight % in a composition means plus or minus up to 20% of the reported weight %.

The term“topical” as used herein to refers to administering the composition(s) of the present invention topically on the skin of a subject.

The term “composition” as used herein refers to a mixture of one or more pharmaceutically acceptable excipient(s) with one or more active agent(s) that can be applied to a subject. The term composition is interchangeably used with the formulation.

The composition according to the present invention refers to any topically administrable dosage form(s), without limiting, selected from cream, ointment, gel, emulgel, spray, foam, paste and the like.

The skin disorder(s) according to the present invention is selected from infective skin disorder(s) and non-infective skin disorder(s). The infective skin disorder(s) herein means any skin disorder caused primarily or secondarily by an infective agent such as bacteria, and fungus. The non-infective skin disorder(s) herein means dermatitis, atopic dermatitis, rashes and the like. In some specific aspects, the skin disorder(s) according to the present invention is selected from secondarily infected traumatic skin lesion or impetigo.

The term“ambient temperature” as used herein refers to any temperature point between about 1°C and about 35 °C. In a specific aspect, the ambient temperature is from about 15 °C to about 30 °C.

The term“alginate” as used herein refers to a source for alginates such as sodium alginate, propylene glycol alginate, ammonium alginate, calcium alginate and the like. In some aspects, the alginate refers to sodium alginate and/or calcium alginate.

The term“metal ion” or“cation” as used herein refers to a source of a cation such as calcium, sodium, potassium, magnesium and the like. The metal ion or cation ion source is selected from, but not limited to, sodium chloride, calcium chloride, magnesium chloride, potassium chloride and the like.

The term“spreadable” as used herein refers to a composition is administered without any lumps of polymeric substance easily with or without shear. The action of spreading the composition may be done manually or using a suitable device, and the composition will have a viscosity suitable for spreading the composition at the application site. The mupirocin in the topical pharmaceutical composition (such as a cream, gel, creamogel / emulgel, ointment, paste, unguent, emulsion (water-in-oil emulsion, oil- water-oil emulsion, water-oil-water emulsion, oil-in-water emulsion), liniment, paste, suspension, lotion and the like and foam) may in any form, such as base or a pharmaceutical acceptable salt form.

In one preferred aspect, the mupirocin is in the form of its calcium salt (e.g., mupirocin calcium, which is a hemicalcium salt of mupirocin), such as a mupirocin dihydrate thereof. For example, the mupirocin may be in the form of its dihydrate crystalline calcium hemi-salt (e.g., (aE,2S,3R,4R,5S)-5-[(2S,3S,4S,5S)-2,3-epoxy-5-hydroxy-4 methylhexyl]tetrahydro-3, 4- dihydroxy-P-methyl-2H-pyran-2-crotonic acid, ester with 9-hydroxynonanoic acid, calcium salt (2: 1), dihydrate). Suitably, mupirocin or a salt thereof is present in from 1 to 3% by weight of the composition, for example, about 0.5%, about 1%, about 1.5%, about 2%, about 2.5%, and about 3%, preferably about 1% and about 2% (expressed as the weight of the free acid).

The present invention relates to a topical composition comprising mupirocin or a pharmaceutically acceptable salt(s) and a polymeric substance(s).

In an aspect, the present invention relates to topical composition comprising mupirocin or a pharmaceutically acceptable salt(s); a polymeric substance(s) selected from a group consisting of polymeric substance; an oil component; wherein the composition comprises oil component(s) from about 10% w/w to about 98% w/w.

The polymeric substance(s), according to the present invention, can be interchangeably used to refer gelling agent, that includes, but are not limited to, acacia, alginic acid, bentonite, Carbopols (now known as carbomers), carboxymethyl cellulose, ethylcellulose, gelatin, hydroxyethyl cellulose, hydroxypropyl cellulose, magnesium aluminum silicate (VEEGUM® available from Vanderbilt Minerals, LLC of Norwalk, CT), methylcellulose, poloxamers (PLURONICS®, available from BASF, Ludwigshafen, Germany), PEMULEN® available from Lubrizol, headquartered at Wickliffe, Ohio (copolymers of acrylic acid and C10-C30 alkyl acrylate crosslinked with allyl pentaerythritol), SEPINEO™ P 600 available from SEPPIC, headquartered at Paris, France (Acrylamide / Sodium Acryloyldimethyl taurate copolymer / lsohexadecane / Polysorbate 80), SEPINEO™ D.E.R.M available from SEPPIC, headquartered at Paris, France (Hydroxyethyl Aerylate / Sodium Acryloyldimethyl Taurate Copolymer), SEPINEO PHD 100 available from SEPPIC, headquartered at Paris, France (polyacrylate crosspolymer-6), polyvinyl alcohol, pectin, hyaluronic acid, hyaluronan, sodium hyaluronate, alginic acid, sodium alginate, tragacanth, chitosan, xanthan gum and any combination of any of the foregoing.

In a specific aspect, the polymeric substance is a pH independent polymer i.e., the polymer does not require a "neutralizer" or a pH adjusting chemical to create the gel after the gelling agent has been wetted in the dispersing medium. In a specific aspect, the polymeric substance is a non-ionic pH independent polymer. In a specific aspect, the polymeric substance(s) is selected from polyvinyl alcohol, hyaluronic acid, sodium hyaluronate, hyaluronan, cellulose, alginic acid, sodium alginate, pectin, tragacanth, chitosan, xanthan gum and any combination of any of the foregoing.

In a specific aspect, the polymeric substance(s) is selected from copolymer of ethyl acrylate, methyl ethacrylate and a copolymer of ethyl acrylate, methyl methacrylate and a low content of methacrylic acid ester with quaternary ammonium groups, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, ethylcellulose, cellulose acetate butyrate, cellulose acetate, alginate, chitosan, and xanthan gum.

In some aspects, the polymeric substance is one or more agents selected from polyacrylic acid derivative(s), polyvinyl alcohol, hyaluronic acid, sodium hyaluronate, hyaluronan, cellulose, alginic acid, sodium alginate, pectin, tragacanth, chitosan, xanthan gum and any combination of any of the foregoing.

In some aspects, the polymeric substance(s) is present in the composition from about 0.01% w/w to about 10% w/w based on the total weight of the composition.

In some aspects, the polymeric substance(s) is present in the composition from about 0.01% w/w to about 8% w/w based on the total weight of the composition.

In a preferred aspect, the concentration of polymeric substance(s) is selected from 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, 0.19, 0.2, 0.21, 0.23, 0.24, 0.25, 0.26, 0.27, 0.28, 0.29, 0.3, 0.31, 0.32, 0.33, 0.34, 0.35, 0.36, 0.37, 0.38, 0.39, 0.4, 0.41, 0.42, 0.43, 0.44, 0.45, 0.46, 0.47,

0.48, 0.49, 0.5, 0.51, 0.52, 0.53, 0.54, 0.55, 0.56, 0.57, 0.58, 0.59, 0.6, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.7, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, 0.79, 0.8, 0.81, 0.82, 0.83, 0.84, 0.85, 0.86, 0.87, 0.88, 0.89, 0.9, 0.91, 0.92, 0.93, 0.94, 0.95, 0.96, 0.97, 0.98, 0.99, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3,

4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6, 6.1, 6.2, 6.3,

6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8% w/w based on the total weight of the composition.

In some aspects, the polymeric substance(s) is present in the composition from about 0.05% w/w to about 5% w/w based on the total weight of the composition.

In a preferred aspect, the polymeric substance(s) is SEPINEO™ P 600 (Acrylamide / Sodium Acryloyldimethyl taurate copolymer / lsohexadecane / Polysorbate 80).

In a preferred aspect, the polymeric substance(s) is SEPINEO™ D.E.R.M (Hydroxyethyl Aerylate / Sodium Acryloyldimethyl Taurate Copolymer).

In a preferred aspect, the polymeric substance(s) is sodium alginate and/or calcium alginate and the concentration of the polymeric substance(s) is from about 0.1% w/w to about 15% w/w based on the total weight of the composition.

In a preferred aspect, the polymeric substance(s) is hydroxypropyl cellulose and the concentration of the polymeric substance(s) is from about 0.01% w/w to about 5% w/w based on the total weight of the composition.

In an aspect, the topical composition comprises at least one solvent. Suitable solvents include, but are not limited to, lower alcohols such as ethanol, propanol, isopropanol, butanol or hexanol; polyols such as glycerol (glycerin), propylene glycol, hexylene glycol, diethylene glycol, diethylene glycol monoethyl ether (TRANSCUTOL® P , available from Gattefosse Deutschland, headquartered in Max-Immselmann-Allee 17, 79427 Eschbach), propylene glycol, ethylene glycol, other glycols or its derivatives; n-alkanols such as ethanol; terpenes such as di-terpenes, tri-terpenes, terpen-ols, limonene, terpene-ol, 1-menthol; dioxolane, sulfoxides such as dimethylsulfoxide (DMSO), dimethylformanide, methyl dodecyl sulfoxide; dimethylacetamide, monooleate of ethoxylated glycerides (with 8 to 10 ethylene oxide units), azone (1- dodecylazacycloheptan-2-one), 2-(n-nonyl)-l,3-dioxolane, esters such as isopropyl myristate/palmitate, ethyl acetate, butyl acetate, propylene carbonate, methyl proprionate, capric/caprylic triglycerides, octylmyristate, dodecyl-myristate; fatty alcohol/acids or its esters such as olelyl alcohol, cetyl alcohol, myristyl alcohol, stearyl alcohol, lauryl alcohol, lauric acid, lauryl lactate ketones; amides such as acetamide, oleates such as triolein; various alkanoic acids such as caprylic acid; lactam compounds such as azone; dialkylamino acetates, and any combination of any of the foregoing.

In some aspects, the topical composition comprises one or more solvents selected from water-miscible solvent(s).

In a specific aspect, the solvent(s) is selected from a water-miscible solvent selected from glycol or its derivatives and dimethyl isosorbide. The glycol or its derivatives may be propylene glycol, hexylene glycol, diethylene glycol, diethylene glycol monoethyl ether (TRANSCUTOL® P), propylene glycol, ethylene glycol, polyethylene glycol or any combination of any of the foregoing.

In some aspects, the solvent(s) is present in the composition at from about 0.1% w/w to about 97% w/w based on the total weight of the composition.

In some aspects, the solvent(s) is present up to about 90% w/w based on the total weight of the composition. The solvent can be interchangeably used to refer vehicle.

In some aspects, the topical composition of the present invention comprises a vehicle.

The term“vehicle” as used herein refers to purified water or one or more water- miscible substance(s) that acts as a base or a carrier for the composition. The vehicle component of the composition is present at least about 30% w/w based on the total weight of the composition.

The vehicle component of the topical composition comprises one or more substances selected from water-miscible solvent(s), purified water, combinations thereof. The water-miscible solvent(s) are selected from, but not limited to, ethanol, isopropyl alcohol, propanol, butanol, pentanol, hexanol, ethylene glycol, propylene glycol, polyethylene glycol, butylene glycol, pentylene glycol, hexylene glycol, diethylene glycol monoethyl ether, dimethyl isosorbide, dimethyl sulfoxide, glycofurol, and any combinations thereof.

In some aspects, the vehicle component of the present invention is present from about 30% w/w to about 97% w/w based on the total weight of the composition.

In some aspects, the vehicle component of the present invention is present from about 40% w/w to about 97% w/w based on the total weight of the composition.

In some aspects, the vehicle component of the present invention is present from about 50% w/w to about 97% w/w based on the total weight of the composition.

In some aspects, the vehicle component is a mixture of one or more water-miscible substance(s) in various weight ratios. In one of the aspect, the weight ratio between ethanol, and water is 0: 1 to 1 :0, and weight ratio between ethanol and isopropyl alcohol is 0: 1 or 1 :0 or 1 : 1 or 1:2 or 1:3 or 1:4 or 4: 1 or 3: 1 or 2: 1 and the like.

In one of the aspect, the vehicle comprises ethanol at about 70% w/w based on total weight of the composition.

In one of the aspect, the vehicle comprises isopropyl alcohol at about 70% w/w based on total weight of the composition.

In some aspects, the vehicle component is an alcoholic vehicle selected from ethanol, propylene glycol, isopropyl alcohol, butanol, isobutanol, hexanol, hexylene glycol and any combinations of any forgoing.

In some aspects, the vehicle is purified water or an emulsion base that is selected from the oil-in-water emulsion, or a water-in-oil emulsion.

In some aspects, the vehicle is an oil-in-water emulsion.

In some aspects, the vehicle comprises water and oil in the weight ratio selected from about 0: 100 to about 50:50 that is 0 part of water to 100 parts of oil, and the water portion can increase up to 50 parts with the decrease of 50 parts of oil component. The vehicle may comprises oil to water ratio of at least about 1: 1 or 1.5: 1 or 2: 1 or 2.5: 1 or 3: 1 or 3.5: 1 or 4: 1 or 1 :4 or 1:3.5 or 1:3 or 1:2.5 or 1:2.

In some aspects, the vehicle comprises water and oil in the weight ratio selected from about 0: 100 to about 20:80 that is 0 part of water to 100 parts of oil, and the water portion can increase up to 20 parts with the decrease of 80 parts of oil component.

In some aspects, the vehicle comprises non-aqueous solvents such as ethanol or isopropyl alcohol, or polyethylene glycol(s) such as polyethylene glycol 400.

In some aspects, the topical composition comprises more than one immiscible phase in the composition. For example, the composition can be an emulsion that contains two phases, one is a continuous phase and the other one is a discontinuous phase. For example, the phases can be oil-in-water, water-in-oil, glycol-in-oil, oil-in-glycol, water/glycol-in-oil, and oil-in-water/glycol.

The topical composition may comprise one or more emulsifying agents, such as anionic emulsifying agent(s), cationic emulsifying agent(s), nonionic emulsifying agent, amphoteric emulsifying agent, zwitterionic emulsifying agent and any combination of any of the foregoing. Suitable emulsifying agent(s) include, but are not limited to, sorbitan fatty acid esters which are a series of mixtures of partial esters of sorbitol and its mono-and dianhydrides with fatty acids. Sorbitan esters include products sold under ARLACEL available from CORADA, headquartered in Snaith, United Kingdom, ARLACEL® 20, ARLACEL® 40, ARLACEL® 60, ARLACEL® 80, ARLACEL 83, ARLACEL 85, ARLACEL 987, and any combination of any of the foregoing. Examples of further suitable emulsifying agents include, but are not limited to, disodium cocoampho diacetate, oxyethylenated glyceryl cocoate (7 EO), PEG-20 hexadecenyl succinate, PEG- 15 stearyl ether, ricinoleic monoethanol amide monosulfosuccinate salts, oxyethylenated hydrogenated ricinoleic triglyceride containing 60 ethylene oxide units such as the products sold by BASE under the trademarks CREMOPHOR® RH 60 or CREMOPHOR® RH 40 (polyoxyl 40 hydrogenated castor oil), polymers such as poloxamers, which are block copolymers of ethylene oxide and propylene oxide, and the nonsolid fatty substances at room temperature (that is to say, at temperatures ranging from about 20 to 35°C) such as sesame oil, sweet almond oil, apricot stone oil, sunflower oil, octoxyglyceryl palmitate (or 2-ethylhexyl glyceryl ether palmitate), octoxyglyceryl behenate (or 2-ethylhexyl glyceryl ether behenate), dioctyl adipate, and tartrates of branched dialcohols. Polyethylene glycol ethers of stearic acid are in another group of emulsifiers that can be used in the emulsions. Examples of polyethylene glycol ethers of stearic acid are steareth-2, steareth-4, steareth-6, steareth-7, steareth-10, steareth-11, steareth-13, steareth-15, steareth-20, polyethylene glycol ethers of stearyl alcohol (steareth 21), and any mixtures thereof. Other emulsifying agents include sodium lauryl sulphate, cetyl trialkyl ammonium bromide, polyoxyethylene sorbitan fatty acid esters, sodium lauryl sulfate, ammonium lauryl sulfate, dioctyl sodium sulfosuccinate, sodium dodecyl benzenesulfonate, sodium dodecyl sulfate, potassium lauryl sulfate; disodium laureth sulfosuccinate, sodium lauroyl sarcosinate, glycerides such as PEG-6 caprylic/capric glycerides, betaines such as cocamidopropyl betaine; ethoxylates such as PEG- 10 soya sterol, amides such as cocamide DEA, myristamide DEA, or PEG-20 methyl glucose ether disteartate and ethers, sodium myreth sulfate, sodium stearate, stearyl alcohol, cetyl alcohol, oleyl alcohol, cetostearyl alcohol, poloxamer, polysorbate, sorbitan monostearate, sorbitan tristearate. Other suitable emulsifying agents additionally or alternatively include, but are not limited to, hydrophilic surfactants such as PEG 400 monooleate, PEG 400 monostearate, potassium oleate, sodium oleate, Polyoxyethylene sorbitan monolaurate (Tween 20), Polyoxyethylene sorbitan monolaurate (Tween 21), Polyoxyethylene sorbitan monopalmitate (Tween 40), Polyoxyethylene sorbitan monostearate (Tween 60), Polyoxyethylene sorbitan monostearate (Tween 61), Polyoxyethylene sorbitan tristearate (Tween 65), Polyoxyethylene sorbitan monooleate (Tween 80), Polyoxyethylene sorbitan monooleate (Tween 81), Polyoxyethylene sorbitan trioleate (Tween 85), cocabetaine, ammonium laureth and any combination of any of the foregoing.

In an aspect, the emulsifying agent is present at a concentration of from about 0.1% w/w to about 20% w/w based on the total weight of the composition. In some aspects, the concentration of emulsifying agent is from about 0.5% w/w to about 17% w/w or from about 0.5% w/w to about 15% w/w or from about 0.5% to about 13%w/w or from about 0.5% w/w to about 12% w/w or from about 0.5% w/w to about 10% w/w based on the total weight of the composition. In a preferred aspect, the emulsifying agent is selected from polyoxy 20 cetosatearyl ether, polysorbate, sorbitan monostearate, cetostearyl alcohol and any combinations thereof. In a preferred aspect, the emulsifying agent is selected from polyoxy 20 cetosatearyl ether, polysorbate, sorbitan monostearate, cetostearyl alcohol and any combinations thereof and the concentration of emulsifying agent is from about 0.1% w/w to about 20% w/w based on the total weight of the composition. In some aspects, the topical composition of the present invention is physically and chemically stable.

In some aspects, the topical composition of the present invention is physically stable without phase separation, particle growth, and sedimentation at least for about 1 month at room temperature. In some aspects, the topical composition of the present invention is stable for at least about 1 month at 25°C and 60% RH.

In some aspects, the topical composition of the present invention is stable for at least about 3 months at 25°C and 60% RH.

In some aspects, the topical composition of the present invention is stable for at least about 3 months at 30°C and 65% RH.

In some aspects, the topical composition of the present invention is stable for at least about 1 month at 40°C and 75% RH.

In some aspects, the topical composition of the present invention does not change the uniformity of the mupirocin in the composition not more than about 10% in ambient temperature.

In some aspects, the viscosity of the topical composition is in the range of from about 1 cps to about 10000 cps when tested in the Brookfield Viscometer Cap 2000+, spindle no. 1, in 5 rpm per 30 seconds at 25 °C (± 0.5°C). In some aspects, the viscosity of the topical composition is in the range of from about 1 cps to about 5000 cps when tested in the Brookfield Viscometer Cap 2000+, spindle no. 1, in 5 rpm per 30 seconds at 25 °C (± 0.5°C).

In some aspects, the viscosity of the topical composition is in the range of from about 1 cps to about 3000 cps when tested in the Brookfield Viscometer Cap 2000+, spindle no. 1, in 5 rpm per 30 seconds at 25 °C (± 0.5°C).

In some aspects, the viscosity of the topical composition is in the range of from about 1 cps to about 100000 cps.

In some aspects, the viscosity of the topical composition is in the range of from about 1 cps to about 50000 cps.

In some aspects, the topical composition comprises one or more emollient(s). Suitable emollients include, but are not limited to, oils of natural origin such as almond oil, coconut oil, olive oil, palm oil, peanut oil and the like, fatty acids such as oleic acid, lauric acid, myristic acid, palmitic acid, and stearic acid, monohydric alcohol esters of the fatty acids such as ethyl laurate, isopropyl laurate, ethyl myristate, n-propyl myristate, isopropyl myristate, ethyl palmitate, isopropyl palmitate, methyl palmitate, methyl stearate, ethyl stearate, isopropyl stearate, butyl stearate, isobutyl stearate, amyl stearate, and isoamyl stearate, glycols such as ethylene glycol, diethylene glycol, and polyethylene glycol, mineral oil and any combination of any of the foregoing. In some aspects, the emollient(s) may be interchangeably used as a moisturizer(s). Emollient(s) soften and soothe the skin. They are used to correct dryness and scaling of the skin. For example, glycerin or glycerol, glycol(s) or its derivatives may act as an emollient in the composition. One of the aspect, the improved mupirocin formulation provides a moisturizing effect to the wounds which indeed helps in the healing and preventing itching of the wounds. In some aspects, the emollient is interchangeably used to refer oil component(s), water-immiscible substance(s), or any substance that prevent transepidermal water loss upon application on the skin of a subject.

In a preferred aspect, one or more emollient is selected from the group of mineral oil, oleic acid, medicum-chain triglyceride, and isopropyl myristate.

In some aspects, the oil component as used herein refers to a water-immiscible substance(s) that are selected from, but not limited to, oils of natural origin such as almond oil, coconut oil, olive oil, palm oil, peanut oil and the like, fatty acids such as oleic acid, lauric acid, myristic acid, palmitic acid, and stearic acid, monohydric alcohol esters of the fatty acids such as ethyl laurate, isopropyl laurate, ethyl myristate, n-propyl myristate, isopropyl myristate, ethyl palmitate, isopropyl palmitate, methyl palmitate, methyl stearate, ethyl stearate, isopropyl stearate, butyl stearate, isobutyl stearate, amyl stearate, and isoamyl stearate, glycols such as ethylene glycol, diethylene glycol, polyethylene glycol, and propylene glycol, linear or branched aliphatic alcohols such as lauryl alcohol, myristyl alcohol, and stearyl alcohol, and mixture of fatty alcohols comprising cetyl and stearyl alcohols such as cetearyl alcohol, mineral oil and any combination of any of the foregoing.

In an aspect, the present invention relates to a topical composition comprising mupirocin or a pharmaceutically acceptable salt(s) and one or more other components selected from a group consisting of polymeric substance, an oily component, a penetration enhancer, an emollient, a plasticizer and an alcoholic vehicle.

Polymeric substance provides a reduced interaction with other components of the composition and stabilize the topical composition against the change in pH and enzymatic degradation. The polymeric substance may also be used as thickening agents; provide an excellent bio-adhesion and film-formation.

In one of the aspect, the present invention relates to topical composition comprising mupirocin or a pharmaceutically acceptable salt(s) and a polymeric substance selected from a group consisting of copolymer of ethyl acrylate, methyl ethacrylate and a copolymer of ethyl acrylate, methyl methacrylate and a low content of methacrylic acid ester with quaternary ammonium groups, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, ethylcellulose, cellulose acetate butyrate and cellulose acetate. In a specific aspect, the polymeric substance is hydroxypropyl cellulose.

In another aspect, the present invention relates to topical composition comprising mupirocin or a pharmaceutically acceptable salt(s) and a polymeric substance; wherein the polymeric substance is present in an amount from about 5% to about 50% or from about 1 % to about 10% or from about 0.1 % to about 1 % by weight of the composition.

In another aspect, the present invention relates to topical composition comprising mupirocin or a pharmaceutically acceptable salt(s), a polymeric substance and an oily component selected from a group consisting of a mineral oil, cyclomethicone, oleic acid, isopropyl myristate, medium chain triglyceride, soya-bean oil, cotton oil, sesame oil, peanut oil and mixtures thereof.

The oily component may provide a skin occlusion especially in the film formation and help in the release of the active ingredient over prolonged time from the resulting film. It also acts as an emollient to improve hydration of the skin and control transepidermal water loss.

In another aspect, the present invention relates to topical composition comprising mupirocin or a pharmaceutically acceptable salt(s), a polymeric substance and an oily component; wherein the oily component is present in an amount from about 1% to about 60% or from about 5% to about 40% or from about 10% to about 25% by weight of the composition.

In another aspect, the present invention relates to a topical composition comprising i) mupirocin or a pharmaceutically acceptable salt(s), ii) a polymeric substance and iii) a penetration enhancer. Penetration enhancers increase skin permeability, appear to act selectively on the extracellular lipids representing the principal regulatory channel for the penetration of actives.

In another aspect, the present invention relates to topical composition comprising i) mupirocin or a pharmaceutically acceptable salt(s), ii) a polymeric substance and iii) a penetration enhancer selected from a group consisting of oleic acid capric acid, myristic acid, lauric acid, diethyl sebacate, isopropyl palmitate, diethylene glycol monoethyl ether, dimethyl isosorbide, L-Menthol, dimethyl sulfoxide and dimethyl formamide. In another aspect the non-aqueous penetration enhancer is selected from a group consisting of oleic acid, lauric acid, isopropyl palmitate, and diethylene glycol monoethyl ether.

In another aspect, the present invention relates to a topical composition comprising i) mupirocin or a pharmaceutically acceptable salt(s), ii) a polymeric substance and iii) a penetration enhancer; wherein the penetration enhancer is present from about 1 % to about 60% or from about 5% to about 40% or from about 10% to about 25% by weight of the composition.

In another aspect, the present invention relates to a topical composition comprising i) mupirocin or a pharmaceutically acceptable salt(s), ii) a polymeric substance and iii) an emollient.

In another aspect, the present invention relates to a topical composition comprising i) mupirocin or a pharmaceutically acceptable salt(s), ii) a polymeric substance and iii) an emollient selected from a group consisting of petrolatum; mineral oils; soybean oil; esters such as isopropyl myristate, isopropyl palmitate and cyclic dimethyl polysiloxane.

In another aspect, the present invention relates to a topical composition comprising i) mupirocin or a pharmaceutically acceptable salt(s), ii) a polymeric substance and iii) an emollient; wherein the emollient is present or from about 1% to about 45% or from about 2% to about 30% or from about 5% to about 15% by weight of the composition.

In another aspect, the present invention relates to a topical composition comprising i) mupirocin or a pharmaceutically acceptable salt(s), ii) a polymeric substance and iii) a plasticizer.

In another aspect, the present invention relates to a topical composition comprising i) mupirocin or a pharmaceutically acceptable salt(s), ii) a polymeric substance and iii) a plasticizer selected from a group consisting of tributyl phosphate, trioctyl phosphate, trimethyl citrate, triethyl citrate and acetyl triethyl citrate, dioctyl adipate diethyl adipate, dimethyl phthalate, diethyl phthalate, diethyl sebacate, dipropyl sebacate, glycerol diacetate, glycerol triacetate (triacetin), glycerol monolactate diacetate, ethylene glycol diacetate, ethylene glycol dibutyrate, triethylene glycol diacetate, triethylene glycol dibutyrate and triethylene glycol dipropionate.

In another aspect, the present invention relates to a topical composition comprising i) mupirocin or a pharmaceutically acceptable salt(s), ii) a polymeric substance and iii) a plasticizer; wherein the plasticizer is present in an amount from about 0.01% to about 20% or about 0.1% to about 10% by weight of the composition.

In another aspect, the topical composition comprises i) mupirocin or a pharmaceutically acceptable salt(s) from about 1% to about 10%, ii) a polymeric substance from about 1% to about 10%, and iii) at least one other component selected from one or more of an oily component from about 5% to about 40%, a penetration enhancer from about 10% to about 25%; an emollient from about 5% to about 15%, a plasticizer from about 0.1% to about 10% by weight of the composition.

In another aspect, the topical composition comprises mupirocin or a pharmaceutically acceptable salt(s) is in the form of a cream, gel, ointment, lotion, spray, foam. In a preferred aspect, the topical composition of the present invention is in the form of gel, lotion or spray. In a still preferred aspect, the topical composition of the present invention is in the form of a gel. The topical composition comprising mupirocin or a pharmaceutically acceptable salt(s) of the present invention is a stable, film-forming composition. In another aspect the stable, film-forming composition is in the form of gel, cream, emulgel, lotion or spray. Preferably, the stable, film-forming composition is in the form of gel or emulgel or cream.

In a specific aspect, the topical composition comprising: i) mupirocin or a pharmaceutically acceptable salt(s) thereof; ii) from about 0.1% w/w to about 10% w/w of a polymeric substance; iii) from about 0% w/w to about 60% w/w of a penetration enhancer(s); iv) an oil component; and v) optionally purified water from 0% w/w to 60% w/w based on total weight of the composition; wherein the composition comprises oil component(s) from about 20% w/w to about 98% w/w.

In a specific aspect, the topical composition comprises: i) from about 0.1 to about 5 % w/w of mupirocin or a pharmaceutically acceptable salt(s) thereof; ii) a polymeric substance comprises from about 0.1% w/w to about 10% w/w of hydroxypropyl cellulose; iii) a penetration enhancer comprises from about 0.1% w/w to about 50% w/w of oleic acid; iv) optionally, an emollient is selected from medium-chain triglyceride, isopropyl myristate, and cyclomethicone; v) from about 10% w/w to about 99% w/w of a vehicle; wherein the composition has film-forming and/or bioadhesive property.

In a specific aspect, the topical composition comprises: i) from about 0.1 to about 5 % w/w of mupirocin or a pharmaceutically acceptable salt(s) thereof; ii) a polymeric substance comprises from about 0.1% w/w to about 10% w/w of hydroxypropyl cellulose; iii) a penetration enhancer comprises from about 0.1% w/w to about 50% w/w of oleic acid; iv) from about 10% w/w to about 99% w/w of isopropyl alcohol; wherein the composition has film-forming and/or bioadhesive property.

In a specific aspect, the topical composition comprising: i) mupirocin or a pharmaceutically acceptable salt(s) thereof; ii) from about 0.1% w/w to about 10% w/w of a polymeric substance(s) selected from copolymer of ethyl acrylate, methyl ethacrylate and a copolymer of ethyl acrylate, methyl methacrylate and a low content of methacrylic acid ester with quaternary ammonium groups, hydroxypropyl cellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, ethylcellulose, cellulose acetate butyrate, cellulose acetate, alginate, chitosan and xanthan gum; iii) from about 0% w/w to about 60% w/w of a penetration enhancer(s); iv) an oil component; and v) purified water from about 0% w/w to about 50% w/w based on total weight of the composition; wherein the composition comprises oil component(s) from about 20% w/w to about 98% w/w.

In a specific aspect, the topical composition comprising: i) about 2%w/w of mupirocin or a pharmaceutically acceptable salt(s) thereof; ii) about 2.5% w/w of hydroxypropyl cellulose; iii) about 21% w/w of oleic acid; and vi) about from about 70% to about 76%w/w of isopropyl alcohol.

In some aspects, the present invention relates to a topical composition comprising: i) mupirocin or a pharmaceutically acceptable salt(s); ii) alginate; iii) a metal ion; and iv) one or more pharmaceutically acceptable excipient(s) thereof.

In some aspects, the topical composition comprises i) mupirocin or a pharmaceutically acceptable salt(s); ii) alginate; iii) a metal ion; and iv) one or more pharmaceutically acceptable excipient(s) thereof; wherein the composition is not microsphere formulation.

In a specific aspect, the present invention relates to a topical composition comprising: i) mupirocin or a pharmaceutically acceptable salt(s); ii) an alginate; iii) a metal ion; and iv) one or more pharmaceutically acceptable excipient(s) thereof; wherein the alginate is selected from sodium alginate, propylene glycol alginate, ammonium alginate, and calcium alginate; and the metal ion is selected from a source of cation and is selected from calcium, sodium, potassium, and magnesium.

In a specific aspect, the present invention relates to a topical composition comprising: i) from about 0.1 to about 5 % w/w of mupirocin or a pharmaceutical acceptable salt(s) thereof; ii) about 1 to about 10 % w/w of sodium alginate; iii) about 0.5 % to about 5% w/w of calcium chloride or suitable hydrate thereof; iv) about 0.5 to about 5% w/w of benzyl alcohol; v) about 0.5% to about 10% w/w of polyoxyl 20 cetostearyl ether, vi) about 1 to about 10% w/w of acrylamide / sodium acryloyldimethyltaurate copolymer / isohexadecane / polysorbate 80; vii) about 5% to about 50% w/w of a mineral oil; and viii) about 50% to about 95% w/w/ of purified water.

In a specific aspect, the topical composition comprises: mupirocin or a pharmaceutically acceptable salt(s) thereof; i) an alginate selected from sodium alginate, calcium alginate and any combinations thereof; ii) calcium chloride; and iii) one or more pharmaceutically acceptable excipient(s) for the treatment and/or prevention of infective skin disorder(s).

In a specific aspect, the topical composition comprises: i) mupirocin or a pharmaceutically acceptable salt(s) thereof; ii) an alginate selected from sodium alginate, calcium alginate and any combinations thereof; iii) calcium chloride; and iv) one or more pharmaceutically acceptable excipient(s) for the treatment and/or prevention of impetigo.

In a specific aspect, the topical composition comprises: i) mupirocin or a pharmaceutically acceptable salt(s) thereof; ii) an alginate selected from sodium alginate, calcium alginate and any combinations thereof; iii) calcium chloride; and iv) one or more pharmaceutically acceptable excipient(s) for the treatment and/or prevention of secondarily infected traumatic skin disorder.

In an aspect, the present invention relates to a topical composition comprising a low dose of mupirocin and at least one occlusive agent; wherein the low dose of mupirocin is less than about 2% w/w based on the total weight of the composition. The low dose of mupirocin, according to the present invention, means about 10% less than originally approved dose of mupirocin i.e., about 2%, or about 20% less than originally approved dose of mupirocin, or about 30% less than originally approved dose of mupirocin, about 40% less than originally approved dose of mupirocin, or about 50% less than originally approved dose of mupirocin or about 60% less than originally approved dose of mupirocin.

The low dose of mupirocin is selected from about 1.9%, or 1.8% or 1.7% or 1.6% or 1.5% or 1.4% or 1.3% or 1.2% or 1.1% or 1% or 0.9% or 0.8% w/w based on total weight of the composition. In some aspects, the topical composition comprises: i) about 0.1% w/w to about 3.0% w/w mupirocin or a pharmaceutically acceptable salt(s) thereof; ii) about 0.01% w/w to about 10% w/w sodium alginate; iii) about 0.01% w/w to about 20% w/w calcium chloride; and iv. water.

In some aspects, the topical composition comprises: i) about 0.1% w/w to about 3.0% w/w mupirocin or a pharmaceutically acceptable salt(s) thereof; ii) about 0.01% w/w to about 5% w/w sodium alginate; iii) about 0.01% w/w to about 5% w/w calcium chloride; and iv. water.

In some aspects, the topical composition comprises: i) about 0.1% w/w to about 3.0% w/w mupirocin or a pharmaceutically acceptable salt(s) thereof; ii) about 0.01% w/w to about 10% w/w sodium alginate; iii) about 0.01% w/w to about 20% w/w calcium chloride; iv) a gelling agent; and v) water.

In some aspects, the topical composition comprises: i) about 0.1% w/w to about 3.0% w/w mupirocin or a pharmaceutically acceptable salt(s) thereof; ii) about 0.01% w/w to about 5% w/w sodium alginate; iii) about 0.01% w/w to about 5% w/w calcium chloride; iv) a gelling agent; and v) water. In some aspects, the topical composition comprises: i) about 0.1%w/w to about 3.0% w/w mupirocin or a pharmaceutically acceptable salt(s) thereof; ii) an aqueous phase comprising: about 0.01% to about 10% w/w sodium alginate; and about 0.01% w/w to about 20% w/w calcium chloride; iii) an oil phase; and iv) water. In some aspects, the topical composition comprises: i) about 0.1% w/w to about 3.0% w/w mupirocin or a pharmaceutically acceptable salt(s) thereof; ii) an aqueous phase comprising: about 0.01% w/w to about 5% w/w sodium alginate; and about 0.01% w/w to about 5% w/w calcium chloride; iii) an oil phase; and iv) water.

In some aspects, the topical composition comprises: i) about 0.1% w/w to about 3.0% w/w mupirocin or a pharmaceutically acceptable salt(s) thereof; ii) about 0.01% w/w to about 10% w/w sodium alginate; iii) about 0.01% w/w to about 20% w/w calcium chloride; and iv) water; wherein weight ratio between sodium alginate to calcium chloride is from about 0.1: 1 to about 1 :2.

In some aspects, the topical composition comprises: i) about 0.1% w/w to about 3.0% w/w mupirocin or a pharmaceutically acceptable salt(s) thereof; ii) an aqueous phase comprising: about 0.01% w/w to about 10% w/w sodium alginate; and about 0.01% w/w to about 20% w/w calcium chloride; iii) an oil phase; iv) an emulsifying agent; and v) water; wherein weight ratio between sodium alginate to calcium chloride is from about 0.1: 1 to about 1:2. In a specific aspect, the topical composition comprises: i) about 0.1% w/w to about 3.0% w/w mupirocin or a pharmaceutically acceptable salt(s) thereof; ii) an aqueous phase comprising: about 0.01% w/w to about 10% w/w sodium alginate, about 0.01% w/w to about 20% w/w calcium chloride, and a gelling agent; iii) one or more emulsifying agent selected from polysorbate, and polyoxyl-20-cetostearyl ether; iv)an oil phase comprising: mineral oil and cetostearyl alcohol; v) one or more preservative(s) selected from benzyl alcohol, sorbitan monostearate, and pheoxyethanol.

In a specific aspect, the topical composition comprises: i) about 0.1% w/w to about 3.0% w/w mupirocin or a pharmaceutically acceptable salt(s) thereof; ii) an aqueous phase comprising: about 0.01% w/w to about 5% w/w sodium alginate, about 0.01% w/w to about 5% w/w calcium chloride, and a gelling agent; iii) one or more emulsifying agent selected from polysorbate, and polyoxyl-20-cetostearyl ether; iv)an oil phase comprising: mineral oil and cetostearyl alcohol; v) one or more preservative(s) selected from benzyl alcohol, sorbitan monostearate and pheoxyethanol.

In an aspect, the topical composition according to the present invention have percentage relative standard deviation less than 10% at least for six months.

In an aspect, the topical composition is chemically stable at least for about 1 month in the ambient temperature. In an aspect, the topical composition is chemically stable at least for about 3 month in the ambient temperature.

In a specific aspect, the topical composition comprises i) from about 0.1% w/w to about 3% w/w mupirocin or pharmaceutical acceptable salt(s) thereof, ii) sodium alginate of from about 1% w/w to about 10% w/w; iii. calcium chloride or suitable hydrate thereof of from about 0.5% w/w to about 20% w/w; iv) benzyl alcohol of from about 0.5 to about 5 % w/w; v) polyoxyl 20 cetostearyl ether of from about 0.5% w/w to about 10% w/w, vi) from about 1% w/w to about 10 % w/w by weight of acrylamide / sodium acryloyldimethyltaurate copolymer/isohexadecane/polysorbate 80, vii) from about 5% w/w to about 50% w/w by weight of a mineral oil, and vii) from about 30% w/w to about 95% w/w of purified water. In a specific aspect, the topical composition comprises i) from about 0.1% w/w to about 3% w/w mupirocin or pharmaceutical acceptable salt(s) thereof, ii) sodium alginate of from about 1% w/w to about 5% w/w; iii) calcium chloride or suitable hydrate thereof of from about 0.5 to about 5 % w/w; iv) benzyl alcohol of from about 0.5% w/w to about 5% w/w; v) polyoxyl 20 cetostearyl ether of from about 0.5% w/w to about 10 % w/w, vi. from about 1% w/w to about 10% w/w by weight of acrylamide / sodium acryloyldimethyltaurate copolymer/isohexadecane/polysorbate 80, vi) from about 5 to about 50% by weight of a mineral oil, and vii) from about 30% to about 95% of purified water. In a specific aspect, the topical composition comprises i) from about 0.1% w/w to about 3% w/w mupirocin or pharmaceutical acceptable salt(s) thereof, ii) sodium alginate of from about 1% w/w to about 10% w/w; iii) calcium chloride or suitable hydrate thereof of from about 0.5% w/w to about 20% w/w; iv) polysorbate of from about 0.5% w/w to about 10% w/w; v) cetostearyl alcohol of from about 0.5% w/w to about 10% w/w, vi) from about 5% w/w to about 50% by weight of a mineral oil, and vii) from about 30% w/w to about 95% w/w of purified water.

In a specific aspect, the topical composition comprises i) from about 0.1% w/w to about 3% w/w mupirocin or pharmaceutical acceptable salt(s) thereof, ii) sodium alginate of from about 1% w/w to about 5% w/w; iii) calcium chloride or suitable hydrate thereof of from about 0.5% w/w to about 5% w/w; iv) polysorbate of from about 0.5% w/w to about 10% w/w; v) cetostearyl alcohol of from about 0.5% w/w to about 10% w/w, vi) from about 5% w/w to about 50% w/w by weight of a mineral oil, and vii. from about 30% w/w to about 95% w/w of purified water.

In a specific aspect, the topical composition comprises i) from about 0.1% w/w to about 3% w/w mupirocin or pharmaceutical acceptable salt(s) thereof, ii) sodium alginate of from about 1% w/w to about 10% w/w; iii) calcium chloride or suitable hydrate thereof of from about 0.5% w/w to about 20% w/w; iv) polysorbate of from about 0.5% w/w to about 10% w/w; v) from about 5% w/w to about 50% w/w by weight of mineral oil, and vi) from about 30% w/w to about 95% w/w of purified water.

In a specific aspect, the topical composition comprises i) from about 0.1% w/w to about 3% w/w mupirocin or pharmaceutical acceptable salt(s) thereof, ii) sodium alginate of from about 1% w/w to about 5% w/w; iii) calcium chloride or suitable hydrate thereof of from about 0.5% w/w to about 5% w/w; iv) polysorbate of from about 0.5% w/w to about 10% w/w; v) from about 5% w/w to about 50% w/w by weight of mineral oil, and vi) from about 30% w/w to about 95% w/w of purified water.

In a specific aspect, the topical composition comprises i) from about 0.1% w/w to about 3% w/w mupirocin or pharmaceutical acceptable salt(s) thereof, ii) about 2%w/w of sodium alginate; iii) about 0.66% w/w of calcium chloride or suitable hydrate thereof; iv) about 5%w/w of polysorbate; v) about 25% w/w of mineral oil; vi) about 6%w/w of cetostearyl alcohol; vii) about 5% w/w of polyoxy 20 cetosatearyl ether; viii) about 1% w/w of phenoxyethanol; ix) about 5%w/w of sorbitan monostearate; x) about 2%w/w of a polymer comprising hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer; and xi) from about 30% w/w to about 95% w/w of purified water. The topical composition comprising: i) a low dose of mupirocin; ii) an alginate; and iii) one or more pharmaceutically acceptable excipient(s); wherein the low dose mupirocin composition provides improved therapeutic outcome as compared to about 2% w/w mupirocin composition.

In an aspect, the present invention relates to a method of treating and/or preventing skin disorder in a subject; wherein the method comprises i) administering a topical composition comprising mupirocin or a pharmaceutically acceptable salt(s) to the skin area of a subject in need thereof.

In some aspects, the skin disorder is an infected and/or non-infected wound.

In a specific aspect, the infective skin disorder is impetigo.

In some aspects, the topical composition comprises i) mupirocin or a pharmaceutically acceptable salt(s) thereof; and ii) from about 0.1% w/w to about 10% w/w of a polymeric substance for the prevention and/or treatment of an infective skin disorder in a subject.

In some aspects, the topical composition comprises i) mupirocin or a pharmaceutically acceptable salt(s) thereof; ii) from about 0.1 % w/w to about 10% w/w of a polymeric substance; and iii) an oil component for the prevention and/or treatment of an infective skin disorder in a subject.

In some aspects, use of a topical composition comprising i) mupirocin or a pharmaceutically acceptable salt(s) thereof; and ii) from about 0.1 % w/w to about 10% w/w of a polymeric substance for the prevention and/or treatment of an infective skin disorder in a subject.

In an aspect, the present invention relates to a method of administering topical composition comprising mupirocin; wherein the method comprises steps of i) administering the topical composition comprising mupirocin on the affected skin area of a subject in need thereof; ii) the composition is spread on the applied area to form a thin film to cover the area; wherein the composition is administered minimum once daily to the subject in need thereof.

In an aspect, the present invention relates to a method of administering topical composition comprising mupirocin; wherein the method comprises steps of i) administering the topical composition comprising mupirocin on the affected skin area of a subject in need thereof; ii) the composition is spread on the applied area to form a thin film to cover the area; wherein the composition is administered twice daily to the subject in need thereof. In an aspect, the present invention relates to a method of administering topical composition comprising mupirocin; wherein the method comprises steps of i) administering the topical composition comprising mupirocin on the affected skin area of a subject in need thereof; ii) the composition is spread on the applied area to form a thin film to cover the area; wherein the composition is administered thrice daily to the subject in need thereof.

In an aspect, the present invention relates to a method of administering topical composition comprising mupirocin; wherein the method comprises steps of i) administering the topical composition comprising mupirocin on the affected skin area of a subject in need thereof; ii) the composition is spread on the applied area to form a thin film to cover the area; wherein the composition is administered minimum once daily to the subject in need thereof for a period of a minimum of one day to a maximum of 10 days.

In an aspect, the present invention relates to a method of administering topical composition comprising mupirocin; wherein the method comprises steps of i) administering the topical composition comprising about 2%w/w mupirocin on the affected skin area of a subject in need thereof; ii) the composition is spread on the applied area to form a thin film to cover the area; wherein the composition is administered minimum once daily to the subject in need thereof for a period of a minimum of one day to a maximum of 10 days.

In an aspect, the present invention relates to a method of administering topical composition comprising mupirocin; wherein the method comprises steps of i) administering the topical composition comprising about 2%w/w mupirocin on the affected skin area of a subject in need thereof; ii) the composition is spread on the applied area to form a thin film to cover the area; wherein the composition is administered minimum once daily to the subject in need thereof for a period of minimum of one day to maximum of 10 days and the method is used for treating and/or preventing infective skin disorder(s).

In an aspect, the method of administering topical composition according to the present invention is administered using any suitable applicator device, and composition may be dispensed using a pump device, or an aerosol spray device, or delivered using a propellant as foam.

In an aspect, the present invention relates to a process of preparing a topical composition comprising mupirocin; wherein the process comprises steps of i) preparing excipient phase; ii) preparing mupirocin containing phase; and iii) mixing mupirocin containing phase with excipient phase to prepare the final composition.

In some aspects, the present invention relates to a process of preparing a topical composition comprising mupirocin; wherein the process comprises steps of i) preparing an aqueous phase comprising: at least one occlusive agent; ii) preparing an oil phase comprising: mupirocin and one or more oil substance(s) and iii) preparing biphasic emulsion from dispersions of step i) and ii).

In some specific aspects, the present invention relates to a process of preparing a topical composition comprising mupirocin; wherein the process comprises steps of i) preparing an aqueous phase comprising: at least one occlusive agent; ii) preparing an oil phase comprising: mupirocin and one or more oil substance(s) and iii) preparing biphasic emulsion from dispersions of step i) and ii); wherein at least one occlusive agent is formed in-situ in the aqueous phase.

In an aspect, the present invention relates to a process of preparing a topical composition comprising: mupirocin; wherein the process comprises the steps of i) preparing an aqueous phase comprising: an alginate source; and a cation source selected from calcium chloride, sodium chloride, magnesium chloride, potassium chloride and any combination(s) thereof; ii) preparing an oil phase comprising: mupirocin and one or more water-immiscible substance(s); iii) emulsification of step i) and ii); wherein the composition forms at least one occlusive agent in-situ from alginate source and a cation in the aqueous phase.

In an aspect, the present invention relates to a process of preparing a topical composition comprising: mupirocin; wherein the process comprises the steps of i) preparing an aqueous phase comprising: an alginate source; and a cation source selected from calcium chloride, sodium chloride, magnesium chloride, potassium chloride and any combination(s) thereof; ii) preparing an oil phase comprising: mupirocin and one or more water-immiscible substance(s); iii) emulsification of step i) and ii); wherein the composition forms at least one occlusive agent in-situ from alginate source and an cation in the aqueous phase.

In an aspect, the present invention relates to a process of preparing topical composition comprising mupirocin; wherein the process comprises steps of: i) preparing mupirocin phase by solubilizing mupirocin in a vehicle comprising one or more solvent selected from ethanol, isopropyl alcohol, propanol, butanol, pentanol, hexanol, ethylene glycol, propylene glycol, polyethylene glycol, butylene glycol, pentylene glycol, hexylene glycol, diethylene glycol monoethyl ether, dimethyl isosorbide, dimethyl sulfoxide, glycofurol, and any combinations thereof; ii) dispersing a polymeric substance in the above mupirocin phase; iii) mixing one or more ingredients selected from oil component, penetration enhancer and emollient to form a final composition; and iv) the volume is adjusted using rest of the amount of vehicle to make final composition. In some aspects, the process of preparing topical composition comprising mupirocin; wherein the process comprises steps of: i) preparing an aqueous phase comprising: mixing an alginate, a cation source, and water; ii) preparing an oil phase comprising: mixing one or more water-immiscible substance(s); iii) emulsification of the aqueous phase and the oil phase to form an emulsion; wherein mupirocin is added either to the oil phase before emulsification, or to the emulsion after emulsification and at least one occlusive agent is an alginate, formed in-situ during the preparation of aqueous phase.

In a specific aspect, the aqueous phase is prepared by mixing water, a cation source, and alginate source to prepare the aqueous phase with at least one occlusive agent.

In a specific aspect, the aqueous phase is prepared by mixing water, calcium chloride, and sodium alginate to prepare the aqueous phase with calcium alginate. In a specific aspect, the oil phase is prepared by dispersing mupirocin in a water- immiscible substance(s).

The following examples are provided to enable one skilled in the art to practice the invention and are merely illustrative of the invention. The examples should not be read as limiting the scope of the invention. EXAMPLES

Example 1 : Gel compositions of mupirocin

Eudragit RL 100 - a copolymer of ethyl acrylate, methyl methacrylate and a low content of methacrylic acid ester with quaternary ammonium groups

Example 2: Spray compositions of mupirocin

Eudragit RL 100 - a copolymer of ethyl acrylate, methyl methacrylate and a low content of methacrylic acid ester with quaternary ammonium groups Manufacturing Process for formulations FI to F7

Preparing mupirocin phase: Mupirocin phase was prepared using any one of the vehicle components such as ethanol or isopropyl alcohol (one part) at room temperature. Gelling: The polymeric substance (eudragit RL 100/hydroxy propyl cellulose) was dispersed in the mupirocin phase using vortex stirrer.

The oil component such as oleic acid or medium-chain triglycerides or isopropyl myristate/ triethyl citrate/ cyclomethicone was added to the above dispersion according to the formulation disclosed above the gel.

The remaining amount of vehicle component (ethanol/isopropyl alcohol) was added to make up the volume under stirring.

Example 3: Mupirocin creamogel composition

Manufacturing Process: The manufacturing process followed to prepare the comparative example compositions is briefly given herein: The aqueous phase of the composition was prepared using sodium alginate, one or more emulsifier like cetomacrogol 1000 with the help of water, and the oil phase was prepared using mineral oil, and other water-immiscible substance(s). The aqueous phase and oil phase were mixed for emulsification to prepare the final composition. Mupirocin was added in the composition by dispersing it in the oil phase, however, any suitable modification on addition of mupirocin is possible.

Example 4: Mupirocin Cream composition

Manufacturing Process: The manufacturing process followed to prepare the example compositions was briefly given herein: The aqueous phase of the composition was prepared using sodium alginate, one or more emulsifier like polysorbate 60 with the help of water, and the oil phase was prepared using mineral oil, and other water- immiscible substance(s) like cetostearyl alcohol. The aqueous phase and the oil phase were mixed for emulsification to prepare the final composition. Mupirocin was added in the composition by dispersing it in the oil phase, however, any suitable modification on the addition of mupirocin is possible.

Example 5: Mupirocin Cream composition

Manufacturing Process: Manufacturing Process: The manufacturing process followed to prepare the example composition is briefly given herein: The aqueous phase of the composition was prepared using sodium alginate, calcium chloride, one or more emulsifier like polysorbate 60 with the help of water, and the oil phase were prepared using mineral oil. The aqueous phase and the oil phase were mixed for emulsification to prepare the final composition. Mupirocin was added in the composition by dispersing it in the oil phase, however, any suitable modification on the addition of mupirocin is possible. Example 6: Mupirocin Cream composition

Manufacturing process: The compositions (F8, F9, and F10) of example 7 was prepared by preparing an aqueous phase and an oil phase, and emulsifying both the phases. The aqueous phase was prepared using sodium alginate, calcium alginate, an emulsifier and water, and the oil phase were prepared using mineral oil, polyoxyl-20- 5 cetostearyl ether, and other excipients. The aqueous phase and oil phase emulsified to prepare the final composition. The mupirocin was dispersed in the oil phase, however, any suitable modification on the addition of mupirocin is possible.

Example 7 : Stability report of Example 6 (F8) composition

The prepared composition of example 6(F8) was filled into closed container and 10 exposed to the stability testing conditions 25° C. and 60% relative humidity (RH), 30° C. and 65% RH, and 40° C. and 75% RH for three months and analyses at various storage points are shown in Table 1.

TABLE 1 - Chemical stability

Pseudomomic acid B: 9-[[(2E)-4-[(2S,3R,4R,5R)-5-[(2S,3S,4S,5S)-2,3-epoxy-5-hydroxy-4- methylhexyl]-3,4,5-trihydroxy-3,4,4,6-tetrahydro-2H-pyran-2-yl]-3-methylbut-2-enoyl]oxy]nonanoic acid; Pseudomomic acid C: 9-[[(2E)-4-[(2S,3R,4R,5S)-3,4-dihydroxy-5-[(2E,4R,5S)-5-hydroxy-4- methylhex-2-enyl]-3,4,5,6-tetrahydro-2H-pyran-2-yl]-3-methylbut-2-enoyl]oxy]nonanoic acid;

5 Pseudomomic acid D: (4E)-9-[[(2E)-4-[(2S,3R,4R,5S)-5-[(2S,3S,4S,5S)-2,3-epoxy-5-hydroxy-4- methylhexyl]-3,4-dihydroxy-3,4,5,6-tetrahydro-2H-pyran-2-yl]-3-methylbut-2-enoyl]oxy]non-4-enoic acid; Pseudomonic acid E - 1 l-j(E)-4-[(2S,3R,4R,5S)-3,4-Dihydroxy-5-(j(2S,3S)-3-[(2S,3S)-3-hydrox- ybutan-2-yl]oxiran-2-yl}methyl)tetrahydro-2H-pyran-2-yl]-3-methylbut-2-enoyloxy}undecanoic acid; Pseudomonic Acid F - [2E,8[2S,3S(lS,2S)]]-5,9-Anhydro-2,3,4,8-tetradeoxy-8-[[3-(2-hydroxy-l- 10 methylpropyl)oxiranyl]methyl]-3-methyl-L-talo-non-2-enonic Acid 6-Carboxyhexyl Ester

Conclusion: the tested composition was stable for at least three months in the tested stability conditions, and impurities were within the limits.

The physical stability parameters such as uniformity, pH, and viscosity were evaluated by taking samples from the top, middle, and bottom of the composition.

15 TABLE 2 - Physical stability

Conclusion: the percentage difference of uniformity was within limits all through the testing period.

Claims

We claim:

1. A topical composition comprising: i) mupirocin or a pharmaceutically acceptable salt(s) thereof; ii) from about 0.1 % w/w to about 10% w/w of a polymeric substance selected from hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, ethylcellulose, cellulose acetate butyrate, cellulose acetate, alginate, and chitosan; iii) from about 0% w/w to about 60% w/w of a penetration enhancer(s); iv) an oil component; and v) purified water from about 0% w/w to about 50% w/w based on total weight of the composition; wherein the composition comprises oil component(s) from about 20% w/w to about 95% w/w.

2. The topical composition of claim 1, wherein the composition comprises mupirocin in solubilized form.

3. The topical composition of claim 1, wherein the composition comprises mupirocin in non-solubilized form.

4. The topical composition of claim 1, wherein the penetration enhancer is selected from oleic acid, capric acid, myristic acid, lauric acid, diethyl sebacate, isopropyl palmitate, diethylene glycol monoethyl ether, dimethyl isosorbide, L-Menthol, dimethyl sulfoxide and dimethyl formamide.

5. The topical composition of claim 1, wherein the composition further comprises plasticizer.

6. The topical composition of claim 1, wherein the oil component is selected from mineral oil, isopropyl myristate, petrolatum, medium-chain triglyceride, fatty acid, esters of fatty acid, fatty alcohol, ethers of fatty alcohol and combinations thereof.

7. A topical composition comprising: i) mupirocin or a pharmaceutical acceptable salt(s) thereof; ii) from about 0.1% w/w to about 5%w/w hydroxypropylcellulose; iii) from about 1% w/w to about 40% w/w of one or more penetration enhancer is oleic acid, isopropyl myristate, and medium chain triglycerides; and iv) a vehicle comprising one or more non-aqueous solvent(s) selected from ethanol, isopropyl alcohol, propylene glycol, polyethylene glycol and glycofurol.

8. A topical composition comprising: i) mupirocin or a pharmaceutical acceptable salt(s) thereof; ii) an alginate; iii) a metal ion and iv) one or more pharmaceutically acceptable excipient(s).

9. The topical composition of claim 9, wherein the alginate is selected from sodium alginate, calcium alginate, ammonium alginate, and propylene glycol alginate.

10. The topical composition of claim 9, wherein the metal ion is a source of cation and is selected from calcium, sodium, potassium, and magnesium.

11. A topical composition comprising: i) mupirocin or a pharmaceutical acceptable salt(s) thereof; ii) about 1 to about 10 % w/w of sodium alginate; iii) about 0.5 to about 5% w/w of calcium chloride or suitable hydrate thereof; iv) about 0.5 to about 5% w/w of benzyl alcohol; v) about 0.5 to about 10% w/w of polyoxyl 20 cetostearyl ether, vi) about 1 to about 10% w/w of acrylamide / sodium acryloyldimethyltaurate copolymer / isohexadecane / polysorbate 80; vii) about 5 to about 50% w/w of a mineral oil; and viii) about 50 to about 95% w/w/ of purified water.

12. The topical composition of any preceding claims are spreadable, bioadhesive, and occlusive.