Foamable vehicle and vitamin and flavonoid pharmaceutical compositions thereof

• US 20080069779A1
• Filed: 09/10/2007
• Published: 03/20/2008
• Est. Priority Date: 08/04/2003
• Status: Abandoned Application

• Current Assignee: Foamix Pharmaceuticals, Ltd. (VYNE Therapeutics, Inc.)
• Original Assignee: Foamix Ltd. (VYNE Therapeutics, Inc.)
• Inventors: Schuz, David, Berman, Tal, Friedman, Doron, Tamarkin, Dov, Eini, Meir
• Application Number:
  US11/900,072
• Publication Number:
  US 20080069779A1
• Time in Patent Office: Days
• US Class Current: 424/45
• CPC Class Codes: A61K 2800/522 Antioxidants; Radical scavengers
• CPC Class Codes: A61K 8/046 Aerosols; Foams
• CPC Class Codes: A61K 8/498 having 6-membered rings or their condensed derivatives, e.g. coumarin
• CPC Class Codes: A61K 8/67 Vitamins
• CPC Class Codes: A61K 8/671 Vitamin A; Derivatives thereof, e.g. ester of vitamin A acid, ester of retinol, retinol, retinal
• CPC Class Codes: A61K 8/675 Vitamin B3 or vitamin B3 active, e.g. nicotinamide, nicotinic acid, nicotinyl aldehyde tocopheryl nicotinate A61K8/678
• CPC Class Codes: A61K 8/676 Ascorbic acid, i.e. vitamin C
• 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 9/124 characterised by the propellant
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin
• CPC Class Codes: A61Q 19/08 Anti-ageing preparations
• CPC Class Codes: A61Q 5/006 Antidandruff preparations

Abstract

Vitamin and flavonoid containing compositions are provided that are stable to degradation. Stabilized compositions include one or more features including a hygroscopic solvent at a sufficient concentration to provide an Aw value of the hygroscopic vitamin and or flavonoid containing composition of less than 0.9, antioxidant flavonoids that are preferentially oxidized before the vitamin, preservatives, and hydrocarbon propellants selected to reduce the oxidation potential of the composition.

Claims

1. A foamable hygroscopic vitamin and or flavonoid containing composition comprising:

a. at least one agent selected from the group consisting of vitamins and flavonoids; and

b. at least one hygroscopic solvent at a sufficient concentration to provide an Aw value of the hygroscopic vitamin and or flavonoid containing composition of less than 0.9;

c. a foam stabilizer selected from the group consisting of at least one surface-active agent; and

at least one polymeric agent selected from the group consisting of a bioadhesive agent, a gelling agent, a film forming agent and a phase change agent and mixtures thereof; and

d. a hydrocarbon propellant at a concentration of about 3% to about 25% by weight of the total composition; and

wherein the composition is contained in a pressurized container to which a vacuum was applied prior to filling with a hydrocarbon propellant, is substantially flowable and provides a foam upon release;

wherein applying a vacuum to and filling a canister containing the composition with hydrocarbon propellant contributes to stabilize the agent against degradation.

2. The composition of claim 1, wherein the vitamin is selected from the group consisting of vitamin A, B1, B2, B3, B5, B6, B7, B9, B12, PABA, C, D1, D2, D3, D4, D5, E, K and F combinations thereof.

3. The composition of claim 1, wherein the vitamin or flavonoid is soluble in water.

4. The composition of claim 1, wherein the vitamin or flavonoid is soluble in a hydrophobic solvent.

5. The composition of claim 1, wherein the vitamin is a combination of two or more vitamins selected from the group consisting of vitamin A, B3, C, K, E, and F.

6. The composition of claim 1, wherein the vitamin is a combination of two or more vitamins selected from the group consisting of vitamin A, C, D1, D2, D3, D4, and D5.

7. The composition of claim 1, wherein the flavonoid is selected from the group consisting of flavonols;

flavones flavonones flavan-3-ols anthocyanins and proanthocyanidins.

8. The composition of claim 1, wherein the flavonoid is a single flavonoid, a combination of two or more flavonoids or a synergistic combination of two or more flavonoids and is selected from the group consisting of benzquercin, diosmin, ethoxazorutoside, flavodate, sodium hesperidin, leucocianido, monoxerutin, oxerutin, quercetin, rutoside, rosmarinic acid, kaempferol, myricetin apigenin, luteolin, hesperetin, naringenin, eriodictyol, cyanidin, delphinidin, malvidin, pelargonidin, peonidin, petunidin, catechin, gallocatechin, epicatechin, and epigallocatechin

9. The composition of claim 1, wherein the flavonoid is quercetin and or rosmarinic acid and the vitamin is vitamin A, and or C and or D (D1, D2, D3, D4, or D5) and or E.

10. The composition of claim 1, wherein the vitamin is a combination of two or more vitamins selected from the group comprising vitamin B3, E and C and a derivative thereof.

11. The composition of claim 1 wherein the vitamin, flavonoid or a derivative thereof or combinations thereof improves, stimulates or promotes target site metabolism.

12. The composition of claim 1, further comprising a preservative and/or modulating agent and/or an anti oxidant.

13. The composition of claim 12, wherein the preservative is selected from the group consisting of disodium metabisulfate and sharomix 824 and the modulating agent is EDTA and or optionally a buffering agent.

14. The composition of claim 1, further comprising an additional therapeutic agent.

15. The composition of claim 1, wherein the hygroscopic solvent 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.

16. The foamable composition of claim 15, wherein the polyol is selected from the group consisting of a diol, a triol and a saccharide,

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 and, 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.

17. The foamable composition of claim 15, 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.

18. The foamable composition of claim 15, wherein the hygroscopic solvent comprises a hygroscopic solvent mixture of at least one polyol and at least one PEG.

19. The foamable composition of claim 15, which is non aqueous or substantially non aqueous, also comprising wherein the hygroscopic solvent comprises (1) at least one hygroscopic solvent selected from a diol, a triol and PEG, and (2) at least a secondary hygroscopic solvent, which 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.

20. 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.

21. The composition of claim 1, further comprising up to 10% of water.

22. The composition of claim 1, wherein the composition is substantially non-aqueous and/or substantially alcohol-free.

23. The composition of claim 1, comprising a vitamin, a flavonoid and or a conservational agent, a stabilizer, and solvent comprising water, wherein the flavonoid and or conservational agent can substantially conserve or stabilize the vitamin or ameliorate, reduce or inhibit its breakdown and wherein the vitamin, flavonoid, stabilizer, conservational agent, and solvent provide a composition that is substantially resistant to aging.

24. The composition of claim 1, wherein the vitamin and or flavonoid or derivative thereof or combinations thereof are loaded into microsponges.

25. A foamable composition comprising a stabilized-vitamin, comprising:

a water-unstable vitamin;

an antioxidative flavonoid; and

a foamable carrier comprising;

i. water;

ii. a foam stabilizer selected from the group consisting of at least one surface-active agent; and

at least one polymeric agent selected from the group consisting of a bioadhesive agent, a gelling agent, a film forming agent and a phase change agent and mixtures thereof;

iii. about 0.005% to about 5% conservational agent; and

iv. a propellant at a concentration of about 3% to about 25% by weight of the total composition,

where said foamable carrier reduces the destabilizing effect of water on the vitamin,

wherein the composition is contained in a pressurized container, is substantially flowable and provides a foam upon release.

26. The foamable composition of claim 25, wherein the foamable carrier further comprises a solvent selected from the group consisting of a hydrophilic solvent, a hydrophobic solvent, a polar solvent, a silicone, an emollient and mixtures thereof.

27. The foamable composition of claim 25, wherein the vitamin is selected from the group consisting of vitamin A, B1, B2, B3, B5, B6, B7, B9, B12, PABA, C, D1, D2, D3, D4, D5, E, K and F and a derivative thereof or combinations thereof.

28. The foamable composition of claim 25, wherein the vitamin or flavonoid is soluble in water.

29. The foamable composition of claim 25, wherein the vitamin or flavonoid is soluble in a hydrophobic solvent.

30. The foamable composition of claim 25, wherein the vitamin is a combination of two or more vitamins selected from the group consisting of vitamin A, B3, C, K, E, and F and a derivative thereof.

31. The foamable composition of claim 25, wherein the vitamin is a combination of two or more vitamins selected from the group consisting of vitamin A, C, D1, D2, D3, D4, and D5 and a derivative thereof.

32. The foamable composition of claim 25, wherein the flavonoid is selected from the group consisting of flavonols;

flavones flavonones flavan-3-ols anthocyanins and proanthocyanidins.

33. The foamable composition of claim 25, wherein the flavonoid is a single flavonoid, a combination of two or more flavonoids or a synergistic combination of two or more flavonoids and is selected from the group consisting of benzquercin, diosmin, ethoxazorutoside, flavodate, sodium hesperidin, leucocianido, monoxerutin, oxerutin, quercetin, rutoside, rosmarinic acid, kaempferol, myricetin apigenin, luteolin, hesperetin, naringenin, eriodictyol, cyanidin, delphinidin, malvidin, pelargonidin, peonidin, petunidin, catechin, gallocatechin, epicatechin, and epigallocatechin.

34. The foamable composition of claim 25, wherein the flavonoid is quercetin and or rosmarinic acid and the vitamin is vitamin A, and or C and or D (D1, D2, D3, D4, or D5) and or E or a derivative thereof.

35. The foamable composition of claim 25, wherein the vitamin is a combination of two or more vitamins selected from the group comprising vitamin B3, E and C and a derivative thereof.

36. The composition of claim 25 wherein the vitamin, flavonoid or a derivative thereof or combinations thereof improves, stimulates or promotes target site metabolism.

37. The foamable composition of claim 25, further comprising a preservative and or modulating agent and or an anti oxidant.

38. The foamable composition of claim 37 wherein the preservative is selected from the group consisting of disodium metabisulfate and sharomix 824 and the modulating agent is EDTA and or optionally a buffering agent.

39. The foamable composition of claim 26, wherein the polar solvent is a polyol is selected from the group consisting of a diol, a triol and a saccharide.

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 and, 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.

40. The foamable composition of claim 26, wherein the polar solvent is a 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.

41. The foamable composition of claim 26, wherein the carrier composition comprises a polar solvent mixture of at least one polyol and at least one PEG.

42. The foamable composition of claim 26, which is non aqueous or substantially non aqueous, also comprising wherein the hygroscopic solvent comprises (1) at least one hygroscopic solvent selected from a diol, a triol and PEG, and (2) at least a secondary hygroscopic solvent, which 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.

43. The foamable composition of claim 26, 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 of Carbopol®

934, Carbopol®

940, Carbopol®

941, Carbopol®

980, Carbopol®

981. hydroxypropylcellulose and carbomer.

44. The foamable composition of claim 25, 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 brij 72, brij 721 and brij W1, a sucrose ester, a partial ester of sorbitol, sorbitan monolaurate, sorbitan monolaurate a monoglyceride, a diglyceride, isoceteth-20, a sucrose ester, or selected from the group consisting of steareth 2, glyceryl monostearate/PEG 100 stearate, Glyceryl Stearate, Steareth-21, peg 40 stearate, polysorbate 60, polysorbate 80, sorbitan stearate, laureth 4, Sorbitan monooleate, ceteareth 16 ceteareth 20, steareth 10, steareth 20, ceteth 20, Macrogol Cetostearyl Ether, ceteth 2, PEG-30 Dipolyhydroxystearate, sucrose distearate, polyoxyethylene (100) stearate, PEG 40 stearate, PEG 100 stearate, laureth 4, cetomacrogol ether, Cetearyl alcohol, Cetearyl glucoside, Oleyl alcohol, Steareth-2, Diisopropyl adipate, Capric/caprilic triglicerides, Polysorbate 20;

Polysorbate 80, Montanov 68 (CETEARYL ALCOHOL (and) CETEARYL GLUCOSIDE), Simusol 165 (Glyceryl stearate and PEG-100 stearate). Methyl glucose sequistearate, Peg 30 dipolyhydroxystearate, sucrose stearic acid esters, sorbitan laureth, sorbitan stearate, polyglyceryl-10 laurate, epikuuron 80, span 80 and mixtures thereof.

45. The foamable composition of claim 26, further comprising a foam adjuvant selected from the group consisting of a fatty alcohol, a fatty acid and a hydroxyl fatty acid or liquid wax.

46. The foamable composition of claim 25, further comprising at least one additional therapeutic agent in addition to the vitamin and flavonoid or combinations thereof in a therapeutically effective concentration.

47. The foamable composition of claim 25, wherein the vitamin and flavonoid or combinations thereof are provided in a microsponge.

48. The foamable composition of claim 25, further comprising at least one additional therapeutic agent 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, wound healing agents and wart removers.

49. The foamable composition of claim 46, wherein the at least one additional therapeutic agent is an anti-infective agent.

50. The composition of claim 25, comprising a vitamin, a flavonoid and or a conservational agent, a stabilizer, and solvent comprising water,

wherein the flavonoid and or conservational agent can substantially conserve or stabilize the vitamin or ameliorate, reduce or inhibit its breakdown and

wherein the vitamin, flavonoid, stabilizer, conservational agent, and solvent provide a composition that is substantially resistant to aging.

51. A method of treating a disorder or condition of mammalian subject, comprising:

administering a foam produced from a foamable vitamin and or flavonoid composition to a target site, the composition comprising;

a foamable composition comprising a stabilized-vitamin, comprising;

a therapeutically effective amount of a water-unstable vitamin;

an optional flavonoid; and

a foamable carrier comprising;

i. water;

ii. a foam stabilizer selected from the group consisting of at least one surface-active agent;

at least one polymeric agent selected from the group consisting of a bioadhesive agent, a gelling agent, a film forming agent and a phase change agent and mixtures thereof;

iii. about 0.005% to about 5% conservational agent; and

iv. a propellant at a concentration of about 3% to about 25% by weight of the total composition,

where said foamable carrier reduces the destabilizing effect of water on the vitamin,

wherein the composition is contained in a pressurized container, is substantially flowable and provides a foam upon release.

52. The method of claim 51, wherein the vitamin and or flavonoid or derivative thereof or combinations thereof are loaded into microsponges.

53. The method of claim 51 further comprising an additional therapeutic agent in addition to the vitamin, flavonoid or combinations thereof.

54. The method of claim 51, 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.

55. The method of claim 51, 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 burns, 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.

56. The method of claim 53, wherein the at least one additional therapeutic 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, wound healing agents and wart removers.

57. The method of claim 53, wherein the at least one 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, difluorosone 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.

58. The method of claim 53, wherein the at least one additional therapeutic agent is an anti-infective agent.

59. The method of claim 53, wherein the at least one 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.

60. The method of claim 53, comprising (1) at least one vitamin;

and (2) at least one additional therapeutic agent selected from the group of an antifungal agent, an antimicrobial agent, an antiviral agent, an anti-acne agent, an antipsoriasis agent, a keratolytic agent and an antiacne agent.

61. The method of claim 53, wherein the additional therapeutic 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 D, a vitamin D3 derivative, calcipotriol, calcitriol 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.

62. The method of claim 53, wherein the additional therapeutic 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 D, a vitamin D3 derivative, calcipotriol, calcitriol and antipsoriasis agent, an anti-proliferative agent, an anti-cancer agent, a non-steroidal anti-inflammatory agent, an immunomodulator, an immunosuppressant and an anti-rosacea agent.

63. A method of treating a disorder or condition of mammalian subject, comprising:

administering to a target site a foam produced by release of a foamable vitamin and flavonoid composition from a pressurized canister containing a composition to which a vacuum was applied prior to filling with a hydrocarbon propellant, the composition comprising;

a. a vitamin and/or flavonoid; and

b. a substantially non-aqueous carrier, the carrier comprising

i. about 50% to about 98% of a polar solvent selected from the group consisting of polyols and polyethylene glycols (PEGs);

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

iii. a surface-active agent or foam adjuvant;

iv. 0% to about 5% by weight of at least one polymeric agent;

v. 0% to about 5% of a conservation agent; and

vi. a propellant at a concentration of about 3% to about 25% by weight of the total composition;

wherein applying a vacuum and filling the canister containing the composition with hydrocarbon propellant contributes to stabilize the vitamin against degradation.

64. The method of claim 63, wherein the vitamin and or flavonoid or derivative thereof or combinations thereof are loaded into microsponges.

65. The method of claim 63, further comprising an additional therapeutic agent in addition to the vitamin, and or flavanoid a derivative thereof or combinations thereof.

66. The method of claim 63, 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.

67. The method of claim 63, 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 burns, 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.

68. The method of claim 63, wherein the at least one additional therapeutic 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, wound healing agents and wart removers.

69. The method of claim 63, wherein the at least one 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, difluorosone 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.

70. The method of claim 63, wherein the at least one additional therapeutic agent is an anti-infective agent.

71. The method of claim 63, wherein the at least one 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.

72. The method of claim 63, comprising (1) at least one vitamin;

and (2) at least one additional therapeutic agent selected from the group of an antifungal agent, an antimicrobial agent, an antiviral agent, an anti-acne agent, an antipsoriasis agent, a keratolytic agent and an antiacne agent.

73. The method of claim 63, wherein the additional therapeutic 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 D, a vitamin D3 derivative, calcipotriol, calcitriol 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.

74. The method of claim 63, wherein the additional therapeutic 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 D, a vitamin D3 derivative, calcipotriol, calcitriol and antipsoriasis agent, an anti-proliferative agent, an anti-cancer agent, a non-steroidal anti-inflammatory agent, an immunomodulator, an immunosuppressant and an anti-rosacea agent.

75. A non-aqueous or substantially non aqueous foamable composition, comprising:

ascorbic acid in an amount of up to about 7 wt %;

about 50% to about 98% of a hygroscopic solvent comprising a mixture of at least one polyol and PEG;

at least one of a surfactant and a foam adjuvant selected from the group consisting of fatty alcohol, a fatty acid and a hydroxyl fatty acid or liquid wax; and

a hydrocarbon propellant at a concentration of about 3% to about 25% by weight of the total composition,

wherein said foamable carrier reduces the destabilizing effect of water on the vitamin, and

wherein the composition is contained in a pressurized container, is substantially flowable and provides a foam upon release.