Foamable vehicle and pharmaceutical compositions thereof

• US 20060275218A1
• Filed: 05/09/2006
• Published: 12/07/2006
• Est. Priority Date: 08/04/2003
• Status: Active Grant

• Current Assignee: VYNE Therapeutics, Inc.
• Original Assignee: Foamix Ltd. (VYNE Therapeutics, Inc.)
• Inventors: Besonov, Alex, Friedman, Doron, Tamarkin, Dov, Eini, Meir
• Granted Patent: US 7,704,518 B2
• Time in Patent Office: Days
• US Class Current: 424/45
• CPC Class Codes: A01N 25/16 Foams
• CPC Class Codes: A01N 53/00 Biocides, pest repellants or attractants, or plant growth regulators containing cyclopropane carboxylic acids or derivatives thereof
• 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 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 8/046 Aerosols; Foams
• 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 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: A61K 9/12 Aerosols; Foams A61K9/0043, A61K9/0056, A61K9/006, A61K9/0073 take precedence; spray-films A61K9/7015
• CPC Class Codes: A61K 9/122 Foams; Dry foams edible foams A61K9/0056
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/12 Keratolytics, e.g. wart or anti-corn preparations
• CPC Class Codes: A61P 23/02 Local anaesthetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61Q 19/00 : Preparations for care of the skin

Abstract

A hygroscopic pharmaceutical composition includes at least one hygroscopic substance at a concentration sufficient to provide an Aw value of at least 0.9 and an antiinfective agent. A foamble pharmaceutical carrier includes about 50% to about 98% of a polar solvent selected from the group consisting of a polyol and PEG; 0% to about 48% of a secondary polar solvent; about 0.2% to about 5% by weight of a surface-active agent; about 0.01% to about 5% by weight of at least one polymeric agent; and a liquefied or compressed gas propellant at a concentration of about 3% to about 25% by weight of the total composition.

Claims

1. A hygroscopic pharmaceutical composition comprising:

a. at least one hygroscopic substance at a sufficient concentration to provide an Aw value of the hygroscopic pharmaceutical composition of less than 0.9; and

b. an anti-infective agent.

2. The hygroscopic pharmaceutical composition of claim 1, further comprising at least one component, selected from the group consisting of:

a. about 0.01% to about 5% by weight of at least one polymeric agent selected from a bioadhesive agent, a gelling agent, a film forming agent and a phase change agent; and

b. about 0.2% to about 5% by weight of a surface-active agent.

3. The hygroscopic composition of claim 1, wherein the hygroscopic substance is selected from the group consisting of:

a. polyethylene glycols (PEGs);

b. surfactants comprising PEG;

c. polyols;

d. monosaccharides, disaccharides, oligosaccharides and sugar alcohols in an amount to provide hygroscopic properties; and

e. honey.

4. The composition of claim 1, wherein the Aw value of the composition is selected from the ranges of (1) about 0.8 and about 0.9;

(2) about 0.7 and about 0.8; and

(3) less than about 0.7.

5. The foamable pharmaceutical carrier of claim 1, further comprising up to 10% of water.

6. The foamable pharmaceutical carrier of claim 1, wherein the composition is substantially non-aqueous.

7. The foamable carrier of claim 1, wherein the composition is substantially alcohol-free.

52. The foamable therapeutic composition of claim 51, wherein the anti-infective agent is selected from the group consisting of an antibiotic agent, an antibacterial agent, an antifungal agent, an agent that controls yeast, an antiviral agent and an antiparasitic agent.

53. The foamable therapeutic composition of claim 52, wherein the antifungal agent is selected from the group consisting of a polyene, natamycin, nystatin;

an allylamine, naftifine, terbinafine;

an imidazole, bifonazole, clotrimazole, econazole, fenticonazole, ketocanazole, miconazole, oxiconazole;

a diazole, a triazoles, fluconazole, itraconazole, terconazole, tolnaftate, ciclopirox, undecylenic acid, sulbentine, griseofulvin, Amphotericin B, flucytosine (5FC), a morpholine compound, amorolfine, and the related morpholines and analogs, derivatives and salts thereof, and any combination thereof at a therapeutically effective concentration.

54. The foamable therapeutic composition of claim 52, wherein the antifungal agent is terbinafine.

55. The foamable therapeutic composition of claim 52, wherein the antibacterial agent is selected from the group consisting of a beta-lactam antibiotic, an aminoglycoside, an ansa-type antibiotic, an anthraquinone, an azole, metronidazole, an antibiotic glycopeptide, a macrolide, erythromycin, clindamycin, an antibiotic nucleoside, an antibiotic peptide, polymyxin B, an antibiotic polyene, an antibiotic polyether, an antibiotic quinolone, an antibiotic steroid, fucidic acid, mupirocin, chloramphenicol, a sulfonamide, tetracycline, an antibiotic metal, silver, copper, zinc, mercury, tin, lead, bismuth, cadmium, chromium, an oxidizing agent, iodine, iodate, a periodate, a hypochlorite, a permanganate, a substance that release free radicals and/or active oxygen, a cationic antimicrobial agent, a quaternary ammonium compound, a biguanide, chlorohexidine, a triguanide, a bisbiguanide, a polymeric biguanide, a naturally occurring antibiotic compound and analogs, derivatives, salts, ions and complexes thereof.

8. A foamble pharmaceutical carrier comprising:

a. about 50% to about 98% of a polar solvent selected from the group consisting of (1) a polyol and (2) a polyethylene glycol (PEG);

b. 0% to about 48% of a secondary polar solvent;

c. about 0.2% to about 5% by weight of a surface-active agent;

d. about 0.01% to about 5% by weight of at least one polymeric agent; and

e. a liquefied or compressed gas propellant at a concentration of about 3% to about 25% by weight of the total composition.

9. The foamable carrier of claim 8, further comprising up to 10% of water.

10. The foamable carrier of claim 8, wherein the carrier is substantially non-aqueous.

11. The foamable carrier of claim 8, wherein the polyol is selected from the group consisting of a diol, a triol and a saccharide.

12. The foamable carrier of claim 11, wherein the diol is selected from the group consisting of propylene glycol, butanediol, butenediol, butynediol, pentanediol, hexanediol, octanediol, neopentyl glycol, 2-methyl-1,3-propanediol, diethylene glycol, triethylene glycol, tetraethylene glycol, dipropylene glycol and dibutylene glycol.

13. The foamable carrier of claim 11, wherein the triol is selected from the group consisting of glycerin, butane-1,2,3-triol, butane-1,2,4-triol and hexane-1,2,6-triol.

14. The foamable carrier of claim 8, wherein the polyol comprises at least one diol and at least one triol, and wherein the ratio between the diol and triol is between 9:

1 and 1;

1.

15. The foamable carrier of claim 8, wherein the PEG is selected from the group consisting of PEG 200, PEG 300, PEG 400, PEG 600, PEG 1000, PEG 4000, PEG 6000 and PEG 8000.

16. The foamable carrier of claim 8, wherein the foamable carrier comprises one or more PEGs in a concentration to provide viscosity of less than 12,000 CPs.

17. The foamable carrier of claim 8, wherein the carrier composition comprises a mixture of at least one polyol and at least one PEG.

18. The foamable carrier of claim 8, wherein the secondary polar solvent is selected from the group consisting of dimethyl isosorbide, tetrahydrofurfuryl alcohol polyethyleneglycol, ether, DMSO, a pyrrolidone, N-Methyl-2-pyrrolidone, 1-Methyl-2-pyrrolidinone, ethyl proxitol, dimethylacetamide, a PEG-type surfactant, an alpha hydroxy acid, lactic acid and glycolic acid.

19. The foamable carrier of claim 18, wherein the secondary polar solvent is dimethyl isosorbide.

20. The foamable carrier of claim 8, wherein the carrier composition comprises (1) at least one polar solvent selected from a diol, a triol and PEG, and (2) at least one secondary polar solvent.

21. The foamable carrier of claim 20, wherein the polyol comprises a mixture of at least two polyols.

22. The foamable carrier of claim 8, wherein the polar solvent comprises a mixture of at least one polyol and at least one PEG.

23. The foamable carrier of claim 22, wherein the ratio between the polyol and/or PEG and the secondary polar solvent is between 9:

1 and 1;

1.

24. The foamable carrier of claim 8, wherein the concentration of the polar solvent and the secondary polar solvent is sufficient to provide an Aw value of the hygroscopic pharmaceutical composition of less than 0.9.

25. The foamable carrier of claim 24, wherein the Aw value of the composition is selected from the ranges of (1) about 0.8 and about 0.9;

(2) about 0.7 and about 0.8; and

(3) less than about 0.7.

26. The foamable carrier of claim 8, wherein the composition is substantially alcohol-free.

27. The foamable carrier of claim 8, wherein the polymeric agent is selected from the group consisting of locust bean gum, sodium alginate, sodium caseinate, egg albumin, gelatin agar, carrageenin gum, sodium alginate, xanthan gum, quince seed extract, tragacanth gum, guar gum, cationic guars, hydroxypropyl guar gum, starch, an amine-bearing polymer, chitosan, alginic acid, hyaluronic acid, a chemically modified starch, a carboxyvinyl polymer, polyvinylpyrrolidone, polyvinyl alcohol, a polyacrylic acid polymer, a polymethacrylic acid polymer, polyvinyl acetate, a polyvinyl chloride polymer, a polyvinylidene chloride polymer, methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, hydroxy propylmethyl cellulose, methylhydroxyethylcellulose, methylhydroxypropylcellulose, hydroxyethylcarboxymethylcellulose, carboxymethyl cellulose, carboxymethylcellulose carboxymethylhydroxyethylcellulose, a cationic cellulose PEG 1000, PEG 4000, PEG 6000 and PEG 8000.

28. The foamable carrier of claim 8, wherein the polymeric agent is dispersible in the polyol or in the mixture of a polyol and an additional polar solvent.

29. The foamable carrier of claim 8, wherein the polymeric agent is selected from the group consisting of hydroxypropylcellulose and carbomer.

30. The foamable carrier of claim 8, wherein the polymeric agent is selected from the group consisting of Carbopol®

934, Carbopol®

940, Carbopo®

941, Carbopol®

980 and Carbopol®

981.

31. The foamable carrier of claim 8, wherein the concentration of the polymeric agent is selected such that the viscosity of the composition is less than 12,000 CPs, or less than 10,000 CPs.

32. The foamable carrier of claim 8, wherein the surface active agent has an HLB value between about 7 and 12.

33. The foamable carrier-of claim 8, wherein the surface active comprises at least two surface active agents and the weighted average of their HLB values is between about 7 and about 12.

34. The foamable carrier of claim 33, wherein the surface active agent is selected from the group consisting of PEG 100 stearate, Laureth 4 and cetomacrogol ether.

35. The foamable carrier of claim 8, wherein the composition comprises one or more surface active agents having an HLB value between about 9 and about 14

36. The foamable carrier of claim 8, wherein the composition comprises one or more surface active agents having an HLB value between about 2 and about 9.

37. The foamable carrier of claim 8, wherein the surface active agent comprises a non-ionic surface active agent.

38. The foamable carrier of claim 8, wherein the surface active agent is selected from the group consisting of a polysorbate, polyoxyethylene (20) sorbitan monostearate, polyoxyethylene (20) sorbitan monooleate, a polyoxyethylene fatty acid ester, Myrj 45, Myrj 49, Myrj 52 and Myrj 59;

a polyoxyethylene alkylyl ether, polyoxyethylene cetyl ether, polyoxyethylene palmityl ether, polyethylene oxide hexadecyl ether, polyethylene glycol cetyl ether, brij 38, brij 52, brij 56 and brij W1, a sucrose ester, a partial ester of sorbitol, sorbitan monolaurate, sorbitan monolaurate a monoglyceride, a diglyceride, isoceteth-20 and a sucrose ester.

39. The foamable carrier of claim 38, wherein the surface active agent further comprises an ionic surfactant, selected from the group consisting of a cationic surfactant, a zwitterionic surfactant, an amphoteric surfactant and an ampholytic surfactant.

40. The foamable carrier of claim 39, wherein the surface active agent comprises a mixture of at least one non-ionic surfactant and at least one ionic surfactant in a ratio selected from

a. about 100:

1 to about 6;

1

b. about 1;

1 to about 20;

1.

41. The foamable carrier of claim 8, further comprising a hydrophobic solvent.

42. The foamable carrier of claim 41, wherein the hydrophobic solvent is selected from the group consisting of mineral oil, isopropyl palmitate, isopropyl isostearate, diisopropyl adipate, diisopropyl dimerate, maleated soybean oil, octyl palmitate, cetyl lactate, cetyl ricinoleate, tocopheryl acetate, acetylated lanolin alcohol, cetyl acetate, phenyl trimethicone, glyceryl oleate, tocopheryl linoleate, wheat germ glycerides, arachidyl propionate, myristyl lactate, decyl oleate, ricinoleate, isopropyl lanolate, pentaerythrityl tetrastearate, neopentylglycol dicaprylate/dicaprate, isononyl isononanoate, isotridecyl isononanoate, myristyl myristate, triisocetyl citrate, octyl dodecanol, unsaturated or polyunsaturated oils, such as olive oil, corn oil, soybean oil, canola oil, cottonseed oil, coconut oil, sesame oil, sunflower oil, borage seed oil, syzigium aromaticum oil, hempseed oil, herring oil, cod-liver oil, salmon oil, flaxseed oil, wheat germ oil, evening primrose oils;

essential oils; and

silicone oils, such as dimethicone, cyclomethicone, polyalkyl siloxane, polyaryl siloxane, polyalkylaryl siloxane, a polyether siloxane copolymer and a poly(dimethylsiloxane)-(diphenyl-siloxane) copolymer.

43. The foamable carrier of claim 8, further comprising a foam adjuvant selected from the group consisting of a fatty alcohol, a fatty acid and a hydroxyl fatty acid.

44. The foamable carrier of claim 8, further comprising an additional component selected from the group consisting of an anti perspirant, an anti-static agent, a buffering agent, a bulking agent, a chelating agent, a colorant, a conditioner, a deodorant, a diluent, a dye, an emollient, fragrance, a humectant, an occlusive agent, a penetration enhancer, a perfuming agent, a permeation enhancer, a pH-adjusting agent, a preservative, a skin penetration enhancer, a sunscreen, a sun blocking agent, a sunless tanning agent, and a vitamins.

45. A foamble therapeutic composition comprising:

a. a therapeutically effective concentration of an active agent;

b. about 50% to about 98% of a polar solvent selected from the group consisting of (1) a polyol; and

(2) a polyethylene glycol;

c. 0% to about 48% of a secondary polar solvent;

d. about 0.2% to about 5% by weight of a surface-active agent;

e. about 0.01% to about 5% by weight of at least one polymeric agent; and

f. a liquefied or compressed gas propellant at a concentration of about 3% to about 25% by weight of the total composition.

46. The foamable therapeutic composition of claim 45, further comprising up to 10% of water.

47. The foamable therapeutic composition of claim 45, wherein the carrier is substantially non-aqueous.

48. The foamable therapeutic composition of claim 45, wherein the Aw value of the composition is selected from the ranges of (1) about 0.8 and about 0.9;

(2) about 0.7 and about 0.8; and

(3) less than about 0.7.

49. The foamable therapeutic composition of claim 45, wherein the active agent is selected from the group consisting of active herbal extracts, acaricides, age spot and keratose removing agents, allergen, analgesics, local anesthetics, antiacne agents, antiallergic agents, antiaging agents, antibacterials, antibiotics, antiburn agents, anticancer agents, antidandruff agents, antidepressants, antidermatitis agents, antiedemics, antihistamines, antihelminths, antihyperkeratolyte agents, antiinflammatory agents, antiirritants, antilipemics, antimicrobials, antimycotics, antiproliferative agents, antioxidants, anti-wrinkle agents, antipruritics, antipsoriatic agents, antirosacea agents antiseborrheic agents, antiseptic, antiswelling agents, antiviral agents, anti-yeast agents, astringents, topical cardiovascular agents, chemotherapeutic agents, corticosteroids, dicarboxylic acids, disinfectants, fungicides, hair growth regulators, hormones, hydroxy acids, immunosuppressants, immunoregulating agents, insecticides, insect repellents, keratolytic agents, lactams, metals, metal oxides, mitocides, neuropeptides, non-steroidal anti-inflammatory agents, oxidizing agents, pediculicides, photodynamic therapy agents, retinoids, sanatives, scabicides, self tanning agents, skin whitening agents, asoconstrictors, vasodilators, vitamins, vitamin D derivatives, wound healing agents and wart removers.

50. The foamable therapeutic composition of claim 45, wherein the active agent is selected from the group consisting of alclometasone dipropionate, amcinafel, amcinafide, amcinonide, beclomethasone, beclomethasone dipropionate, betamethsone, betamethasone benzoate, betamethasone dexamethasone-phosphate, dipropionate, betamethasone valerate, budesonide, chloroprednisone, chlorprednisone acetate, clescinolone, clobetasol, clobetasol propionate, clobetasol valerate, clobetasone, clobetasone butyrate, clocortelone, cortisone, cortodoxone, craposone butyrate, desonide, desoxymethasone, dexamethasone, desoxycorticosterone acetate, dichlorisone, diflorasone diacetate, diflucortolone valerate, diflurosone diacetate, diflurprednate, fluadrenolone, flucetonide, flucloronide, fluclorolone acetonide, flucortine butylesters, fludroxycortide, fludrocortisone, flumethasone, flumethasone pivalate, flumethasone pivalate, flunisolide, fluocinolone, fluocinolone acetonide, fluocinonide, fluocortin butyl, fluocortolone, fluorometholone, fluosinolone acetonide, fluperolone, fluprednidene acetate, fluprednisolone hydrocortamate, fluradrenolone, fluradrenolone acetonide, flurandrenolone, fluticasone, halcinonide, halobetasol, hydrocortisone, hydrocortisone acetate, hydrocortisone butyrate, hydrocortisone cyclopentylpropionate, hydrocortisone valerate, hydroxyltriamcinolone, medrysone, meprednisone, .alpha.-methyl dexamethasone, methylprednisolone, methylprednisolone acetate, mometasone furoate, paramethasone, prednisolone, prednisone, pregnenolone, progesterone, spironolactone, triamcinolone, triamcinolone acetonide and derivatives, esters and salts thereof.

51. The foamable therapeutic composition of claim 48, wherein the active agent is an anti-infective agent.

56. The foamable therapeutic composition of claim 47, wherein the active agent is unstable in the presence of water.

57. The foamable therapeutic composition of claim 45, wherein the active agent is a combination of at least two active agents.

58. The foamable therapeutic composition of claim 47, wherein the active agent is a combination of at least two active agents.

59. The foamable therapeutic composition of claim 45, comprising (1) a corticosteroid;

and (2) and active agent selected from the group of an antifungal agent, an antimicrobial agent, an antiviral agent, an anti-acne agent, a vitamin D3 derivative, calcipotriol, and antipsoriasis agent, a keratolytic agent and an antiacne agent.

60. The foamable therapeutic composition of claim 45, comprising (1) a keratolytic agent;

and (2) and active agent selected from the group of a corticosteroid, an antifungal agent, an antimicrobial agent, an antiviral agent, an anti-acne agent, a vitamin D3 derivative, calcipotriol, and antipsoriasis agent, an immunomodulator, and immunosuppressant and an antiacne agent.

61. A method of treating a disorder of mammalian subject, comprising:

administering a foamable therapeutic composition to a target site, the composition comprising;

a. a therapeutically effective concentration of an active agent;

b. about 50% to about 98% of a polar solvent selected from the group consisting of (1) a polyol; and

(2) a polyethylene glycol;

c. 0% to about 48% of a secondary polar solvent;

d. about 0.2% to about 5% by weight of a surface-active agent;

e. about 0.01% to about 5% by weight of at least one polymeric agent; and

f. a liquefied or compressed gas propellant at a concentration of about 3% to about 25% by weight of the total composition

62. The method of claim 61, wherein the target site is selected from the group consisting of the skin, a body cavity, a mucosal surface, the nose, the mouth, the eye, the ear canal, the respiratory system, the vagina and the rectum.

63. The method of claim 61, wherein the disorder is selected from the group consisting of dermatological pain, dermatological inflammation, acne, acne vulgaris, inflammatory acne, non-inflammatory acne, acne fulminans, nodular papulopustular acne, acne conglobata, dermatitis, bacterial skin infections, fungal skin infections, viral skin infections, parasitic skin infections, skin neoplasia, skin neoplasms, pruritis, cellulitis, acute lymphangitis, lymphadenitis, erysipelas, cutaneous abscesses, necrotizing subcutaneous infections, scalded skin syndrome, folliculitis, furuncles, hidradenitis suppurativa, carbuncles, paronychial infections, rashes, erythrasma, impetigo, ecthyma, yeast skin infections, warts, molluscum contagiosum, trauma or injury to the skin, post-operative or post-surgical skin conditions, scabies, pediculosis, creeping eruption, eczemas, psoriasis, pityriasis rosea, lichen planus, pityriasis rubra pilaris, edematous, erythema multiforme, erythema nodosum, grannuloma annulare, epidermal necrolysis, sunburn, photosensitivity, pemphigus, bullous pemphigoid, dermatitis herpetiformis, keratosis pilaris, callouses, corns, ichthyosis, skin ulcers, ischemic necrosis, miliaria, hyperhidrosis, moles, Kaposi'"'"'s sarcoma, melanoma, malignant melanoma, basal cell carcinoma, squamous cell carcinoma, poison ivy, poison oak, contact dermatitis, atopic dermatitis, rosacea, purpura, moniliasis, candidiasis, baldness, alopecia, Behcet'"'"'s syndrome, cholesteatoma, Dercum disease, ectodermal dysplasia, gustatory sweating, nail patella syndrome, lupus, hives, hair loss, Hailey-Hailey disease, chemical or thermal skin bums, scleroderma, aging skin, wrinkles, sun spots, necrotizing fasciitis, necrotizing myositis, gangrene, scarring, and vitiligo, chlamydia infection, gonorrhea infection, hepatitis B, herpes, HIV/AIDS, human papillomavirus (HPV), genital warts, bacterial vaginosis, candidiasis, chancroid, granuloma Inguinale, lymphogranloma venereum, mucopurulent cervicitis (MPC), molluscum contagiosum, nongonococcal urethritis (NGU), trichomoniasis, vulvar disorders, vulvodynia, vulvar pain, yeast infection, vulvar dystrophy, vulvar intraepithelial neoplasia (VIN), contact dermatitis, pelvic inflammation, endometritis, salpingitis, oophoritis, genital cancer, cancer of the cervix, cancer of the vulva, cancer of the vagina, vaginal dryness, dyspareunia, anal and rectal disease, anal abscess/fistula, anal cancer, anal fissure, anal warts, Crohn'"'"'s disease, hemorrhoids, anal itch, pruritus ani, fecal incontinence, constipation, polyps of the colon and rectum;

and wherein the active agent is suitable for treating said disorder.

64. The method of claim 61, wherein the active agent is selected from the group consisting of alclometasone dipropionate, amcinafel, amcinafide, amcinonide, beclomethasone, beclomethasone dipropionate, betamethsone, betamethasone benzoate, betamethasone dexamethasone-phosphate, dipropionate, betamethasone valerate, budesonide, chloroprednisone, chlorprednisone acetate, clescinolone, clobetasol, clobetasol propionate, clobetasol valerate, clobetasone, clobetasone butyrate, clocortelone, cortisone, cortodoxone, craposone butyrate, desonide, desoxymethasone, dexamethasone, desoxycorticosterone acetate, dichlorisone, diflorasone diacetate, diflucortolone valerate, diflurosone diacetate, diflurprednate, fluadrenolone, flucetonide, flucloronide, fluclorolone acetonide, flucortine butylesters, fludroxycortide, fludrocortisone, flumethasone, flumethasone pivalate, flumethasone pivalate, flunisolide, fluocinolone, fluocinolone acetonide, fluocinonide, fluocortin butyl, fluocortolone, fluorometholone, fluosinolone acetonide, fluperolone, fluprednidene acetate, fluprednisolone hydrocortamate, fluradrenolone, fluradrenolone acetonide, flurandrenolone, fluticasone, halcinonide, halobetasol, hydrocortisone, hydrocortisone acetate, hydrocortisone butyrate, hydrocortisone cyclopentylpropionate, hydrocortisone valerate, hydroxyltriamcinolone, medrysone, meprednisone, .alpha.-methyl dexamethasone, methylprednisolone, methylprednisolone acetate, mometasone furoate, paramethasone, prednisolone, prednisone, pregnenolone, progesterone, spironolactone, triamcinolone, triamcinolone acetonide and derivatives, esters and salts thereof.

65. The method of claim 61, wherein the composition is substantially non-aqueous.

66. The method of claim 61, wherein the Aw value of the composition is selected from the ranges of (1) about 0.8 and about 0.9;

(2) about 0.7 and about 0.8; and

(3) less than about 0.7.

67. The method of claim 66, wherein the active agent is an anti-infective agent.

68. The method of claim 67, wherein the anti-infective agent is selected from the group consisting of an antibiotic agent, an antibacterial agent, an antifungal agent, an agent that controls yeast, an antiviral agent and an antiparasitic agent.

69. The method of claim 67, wherein the antifungal agent is selected from the group consisting of a polyene, natamycin, nystatin;

an allylamine, naftifine, terbinafine;

an imidazole, bifonazole, clotrimazole, econazole, fenticonazole, ketocanazole, miconazole, oxiconazole;

a diazole, a triazoles, fluconazole, itraconazole, terconazole, tolnaftate, ciclopirox, undecylenic acid, sulbentine, griseofulvin, Amphotericin B, flucytosine (5FC), a morpholine compound, amorolfine, and the related morpholines and analogs, derivatives and salts thereof, and any combination thereof at a therapeutically effective concentration.

70. The method of claim 67, wherein the antifungal agent is terbinafine.

71. The method of claim 67, wherein the antibacterial agent is selected from the group consisting of a beta-lactam antibiotic, an aminoglycoside, an ansa-type antibiotic, an anthraquinone, an azole, metronidazole, an antibiotic glycopeptide, a macrolide, erythromycin, clindamycin, an antibiotic nucleoside, an antibiotic peptide, polymyxin B, an antibiotic polyene, an antibiotic polyether, an antibiotic quinolone, an antibiotic steroid, fucidic acid, mupirocin, chloramphenicol, a sulfonamide, tetracycline, an antibiotic metal, silver, copper, zinc, mercury, tin, lead, bismuth, cadmium, chromium, an oxidizing agent, iodine, iodate, a periodate, a hypochlorite, a permanganate, a substance that release free radicals and/or active oxygen, a cationic antimicrobial agent, a quaternary ammonium compound, a biguanide, chlorohexidine, a triguanide, a bisbiguanide, a polymeric biguanide, a naturally occurring antibiotic compound and analogs, derivatives, salts, ions and complexes thereof.

72. The method of claim 65, wherein the active agent is unstable in the presence of water.

73. The method of claim 64, wherein the active agent comprises a combination of at least two active agents.

74. The method of claim 65, wherein the active agent comprises a combination of at least two active agents.

75. The method of claim 73, wherein the active agent comprises a combination of (1) a corticosteroid;

and (2) and active agent selected from the group of an anti-infective agent, an antifungal agent, an antimicrobial agent, an antiviral agent, an anti-acne agent, a retinoid, a vitamin D3 derivative, calcipotriol, and antipsoriasis agent, a keratolytic agent, an anti-proliferative agent, an anti-cancer agent, a non-steroidal anti-inflammatory agent, an immunomodulator, an immunosuppressant and an anti-rosacea agent.

76. The method of claim 73, wherein the active agent comprises a combination of (1) a keratolytic agent;

and (2) and active agent selected from the group of a corticosteroid, an anti-infective agent, an antifungal agent, an antimicrobial agent, an antiviral agent, an anti-acne agent, a retinoid, a vitamin D3 derivative, calcipotriol, and antipsoriasis agent, t, an anti-proliferative agent, an anti-cancer agent, a non-steroidal anti-inflammatory agent, an immunomodulator, an immunosuppressant and an anti-rosacea agent.