TOPICAL FORMULATIONS COMPRISING A STEROID

• US 20170360808A1
• Filed: 08/30/2017
• Published: 12/21/2017
• Est. Priority Date: 08/31/2009
• Status: Active Grant

• Current Assignee: Primus Pharmaceuticals Incorporated
• Original Assignee: Dr. Reddy's Laboratories Ltd.
• Inventors: UBAIDULLA, Udhumansha, KANDAVILLI, Sateesh, VAIRALE, Ajay Sunil, WAYNE, Jeffrey A., NALAMOTHU, Vijendra, MEGHAL, Mistry, PAKUNLU, Refika Isil
• Granted Patent: US 9,877,974 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/575 substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/107 Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• CPC Class Codes: A61K 9/7015 Drug-containing film-forming compositions, e.g. spray-on
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/08 Antiseborrheics
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: B05B 1/02 designed to produce a jet, spray, or other discharge of particular shape or nature, e.g. in single drops, or having an outlet of particular shapeB05B1/26, B05B1/28, B05B1/34 take precedence
• CPC Class Codes: B05B 1/30 : designed to control volume of flow, e.g. with adjustable passages B05B11/0094 takes precedence
• CPC Class Codes: B05B 11/1045 : the pump being preassembled as an independent unit before being mounted on the container B05B11/1047, B05B11/1049 take precedence
• CPC Class Codes: B05B 15/30 : Dip tubes

Abstract

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.

Claims

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 μ

m.

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.

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.

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 μ

m.

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.

4. The composition according to claim 4, 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.

6. The composition according to claim 6, 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.

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 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 μ

m 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 μ

m.

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.