Topical formulations comprising a steroid
The application provides formulations for the topical administration of an active agent comprising at least one steroid, in the form of topical sprays that are propellant-free, and/or substantially non-foaming, and/or alcohol-free. The present application also provides processes for preparing such compositions and methods of using them in management of skin diseases or disorders such as psoriasis, dermatoses, and other associated skin diseases or disorders.
1. A topical pharmaceutical composition comprising:
a betamethasone compound;
an emulsifying agent;
water;
a water-immiscible substance; and
a skin penetration enhancer;
wherein the composition is aqueous based emulsion having average particle sizes of the dispersed phase droplets are less than about 500 μm.
2. The composition according to claim 1 , wherein the betamethasone compound is selected from betamethasone benzoate, betamethasone dipropionate, betamethasone sodium phosphate, and betamethasone valerate.
3. The composition according to claim 1 , wherein the emulsifying agent comprises a cationic surfactant, anionic surfactant, zwitterionic surfactant, amphoteric surfactant, or any combination thereof.
4. The composition according to claim 1 , wherein the emulsifying agent is selected from the group comprising of a sorbitan fatty acid ester, a mixture of partial esters of sorbitol and its mono- and di-anhydrides with fatty acids, a polyethylene glycol stearate, a glycol stearate, sodium lauryl sulphate, cetyl trialkyl ammonium bromide, a polyoxyethylene sorbitan fatty acid ester, or any combination thereof.
5. The composition according to claim 1 , wherein the skin penetration enhancer selected from a polyol and esters, ethers, sulfoxides, fatty acids, fatty acid esters, and any combinations thereof.
6. The composition according to claim 1 , wherein the skin penetration enhancer is selected from the group comprising of: butanediol, polyethylene glycol monolaurate, diethylene glycol monoethyl ether, dimethylsulfoxide, decylmethylsulfoxide, lauric acid, oleic acid, valeric acid, isopropyl myristate, isopropyl palmitate, methyl propionate, ethyl oleate, or any combination thereof.
7. The composition according to claim 1 , wherein the water-immiscible substance is selected from the group consisting of vegetable oil, saturated paraffin oil, mineral oil, fatty acid, fatty ester of a natural fatty acid, triglyceride of animal or vegetable origin, medium chain triglyceride, mixture of mono-, di- and/or tri-glycerides, wax, hydrogenated vegetable oil, and any combination thereof.
8. The composition according to claim 1 , wherein the average particle sizes of the dispersed phase droplets is from about 1 to about 500 μm.
9. The composition according to claim 1 , wherein the composition is non-foaming, propylene glycol-free, alcohol-free, and propellant-free.
10. A method of treating a skin condition comprising administering a pharmaceutically effective amount of the composition according to claim 1 to a subject in need thereof, wherein the condition is selected from one or more of the group of conditions consisting of atopic dermatitis, seborrhoeic dermatitis, eczema, plaque psoriasis, erythroderma psoriasis, and psoriasis of the scalp, steroid responsive dermatoses, erythema, and contact sensitivity reactions.
11. A topical pharmaceutical composition comprising:
a betamethasone compound;
an emulsifying agent;
water;
a water-immiscible substance; and
a skin penetration enhancer selected from the group consisting of butanediol, polyethylene glycol monolaurate, diethylene glycol monoethyl ether, dimethylsulfoxide, decylmethylsulfoxide, lauric acid, oleic acid, valeric acid, isopropyl myristate, isopropyl palmitate, methyl propionate, ethyl oleate, and combinations thereof;
wherein the composition is non-foaming, propylene glycol-free, alcohol-free, and propellant-free.
12. The composition according to claim 11 , wherein the betamethasone compound is selected from betamethasone benzoate, betamethasone dipropionate, betamethasone sodium phosphate, and betamethasone valerate.
13. The composition according to claim 12 , wherein the emulsifying agent comprises a cationic surfactant, anionic surfactant, zwitterionic surfactant, amphoteric surfactant, or any combination thereof.
14. The composition according to claim 13 , wherein the emulsifying agent comprises a sorbitan fatty acid ester, a mixture of partial esters of sorbitol and its mono- and di-anhydhdes with fatty acids, a polyethylene glycol stearate, a glycol stearate, sodium lauryl sulphate, cetyl trialkyl ammonium bromide, a polyoxyethylene sorbitan fatty acid ester, or any combination thereof.
15. The composition according to claim 11 , wherein the water-immiscible substance is selected from the group consisting of vegetable oil, saturated paraffin oil, mineral oil, fatty acid, fatty ester of a natural fatty acid, triglyceride of animal or vegetable origin, medium chain triglyceride, mixture of mono-, di- and/or tri-glycerides, wax, hydrogenated vegetable oil, and any combination thereof.
16. The composition according to claim 15 , wherein the water-immiscible substance comprises castor oil, lanolin oil, citrate thisocetyl triglyceride having 10-18 carbon atoms, coconut oil, corn oil, cottonseed oil, linseed oil, oil of mink, olive oil, palm oil, sunflower oil, nut oil, or any combination thereof.
17. The composition according to claim 11 , wherein the composition provides less than about 10% drug release in 1 hour when evaluated using a Franz diffusion cell fitted with polysulphone 0.2 μm membrane, and the receptor media is a mixture of ethanol and water 20:80 by volume with a replacement volume of 12 ml.
18. The composition according to claim 11 , wherein the emulsifying agent is from about 0.25% w/w to about 45% w/w of the composition.
19. The composition according to claim 11 , wherein the skin penetration enhancer is from about 0.001% w/w to about 15% w/w of the composition.
20. A method of treating a skin condition comprising administering a pharmaceutically effective amount of the composition according to claim 11 to a subject in need thereof, wherein the condition is selected from one or more of the group of conditions consisting of atopic dermatitis, seborrhoeic dermatitis, eczema, plaque psoriasis, erythroderma psoriasis, and psoriasis of the scalp, steroid responsive dermatoses, erythema, and contact sensitivity reactions.
21. A composition comprising:
a betamethasone compound;
an emulsifying agent;
water;
a water-immiscible substance; and
a skin penetration enhancer;
wherein the composition is an aqueous-based composition having viscosity in the range of from about 10 to about 15,000 centipoise.
22. The composition according to claim 21 , wherein the betamethasone compound is betamethasone benzoate, betamethasone dipropionate, betamethasone sodium phosphate, or betamethasone valerate.
23. The composition according to claim 21 , wherein the emulsifying agent comprises a cationic surfactant, anionic surfactant, zwitterionic surfactant, amphoteric surfactant, or any combination thereof.
24. The composition according to claim 21 , wherein the skin penetration enhancer selected from a polyol and esters, ethers, sulfoxides, fatty acids, fatty acid esters, and any combinations thereof.
25. The composition according to claim 21 , wherein the water-immiscible substance is selected from the group consisting of a natural fatty acid, triglyceride of animal or vegetable origin, medium chain triglyceride, mixture of mono-, di- and/or tri-glycerides, wax, hydrogenated vegetable oil, and any combination thereof.
26. The composition according to claim 21 , wherein the average particle sizes of the dispersed phase droplets is from about 1 to about 500 μm.
27. The composition according to claim 21 , wherein the composition is non-foaming, propylene glycol-free and alcohol-free.
28. The composition according to claim 21 , wherein the emulsifying agent is from about 0.25% w/w to about 45% w/w of the composition.
29. The composition according to claim 21 , wherein the skin penetration enhancer is from about 0.001% w/w to about 15% w/w of the composition.
30. A method of treating a skin condition comprising administering a pharmaceutically effective amount of the composition according to claim 21 to a subject in need thereof, wherein the condition is selected from one or more of the group of conditions consisting of atopic dermatitis, seborrhoeic dermatitis, eczema, plaque psoriasis, erythroderma psoriasis, and psoriasis of the scalp, steroid responsive dermatoses, erythema, and contact sensitivity reactions.