Foamable composition combining a polar solvent and a hydrophobic carrier

• US 10,117,812 B2
• Filed: 07/19/2006
• Issued: 11/06/2018
• Est. Priority Date: 10/25/2002
• Status: Active Grant

• Current Assignee: VYNE Therapeutics, Inc.
• Original Assignee: Foamix Pharmaceuticals, Ltd. (VYNE Therapeutics, Inc.)
• Inventors: Tamarkin, Dov, Friedman, Doron, Eini, Meir, Besonov, Alex
• Primary Examiner(s): Orwig, Kevin S
• Assistant Examiner(s): Frazier, Barbara S
• Application Number:
  US11/488,989
• Publication Number:
  US 20070020213A1
• Time in Patent Office: 4,493 Days
• Field of Search: None
• CPC Class Codes: A01N 25/16 Foams
• CPC Class Codes: A61K 35/04 Tars; Bitumens; Mineral oils; Ammonium bituminosulfonate
• CPC Class Codes: A61K 47/06 Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
• 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 47/32 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 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 8/046 Aerosols; Foams
• CPC Class Codes: A61K 8/062 Oil-in-water emulsions
• CPC Class Codes: A61K 8/31 Hydrocarbons
• CPC Class Codes: A61K 8/37 Esters of carboxylic acids
• CPC Class Codes: A61K 8/375 the alcohol moiety containing more than one hydroxy group
• CPC Class Codes: A61K 8/4973 with oxygen as the only hetero atom
• CPC Class Codes: A61K 8/731 Cellulose; Quaternized cellulose derivatives
• CPC Class Codes: A61K 8/8176 Homopolymers of N-vinyl-pyrrolidones. Compositions of derivatives of such polymers
• CPC Class Codes: A61K 8/965 of inanimate origin
• 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 9/122 Foams; Dry foams edible foams A61K9/0056
• CPC Class Codes: A61Q 19/00 : Preparations for care of the skin
• CPC Class Codes: A61Q 19/02 : for chemically bleaching or whitening the skin
• CPC Class Codes: A61Q 19/08 : Anti-ageing preparations

Abstract

The present invention relates to a foamable vehicle or cosmetic or pharmaceutical composition, comprising: (1) an organic carrier, at a concentration of 10% to 70% by weight, wherein said organic carrier concurrently comprises: (i) at least one hydrophobic organic carrier, and (ii) at least one polar solvent; (2) at least one surface-active agent; (3) water; and (4) at least one liquefied or compressed gas propellant at a concentration of 3% to 25% by weight of the total composition.

The present invention further provides a method of treating, alleviating or preventing a disorder of mammalian subject, comprising administering the above-mentioned compositions to an afflicted target site.

Claims

1. A foamable pharmaceutical vehicle or composition, comprising:

(1) a liquid organic carrier, at a concentration of 10% to 70% by weight of the composition, wherein said organic carrier concurrently comprises;

(i) at least one hydrophobic organic carrier comprising a triglyceride, and

(ii) at least one polar solvent comprising dimethyl isosorbide,

(2) a surface-active agent selected from the group consisting of at least one non-ionic surface-active agent, and a mixture of a non-ionic surface-active agent and an ionic surface-active agent, wherein the ratio of non-ionic surface-active agent to ionic surface-active agent is greater than 14;

1;

(3) water;

(4) at least one liquefied or compressed gas propellant at a concentration of 3% to 25% by weight of the total composition; and

(5) a polymeric agent selected from the group consisting of a locust bean gum, sodium caseinate, an egg albumin, a gelatin agar, a carrageenin gum, sodium alginate, a xanthan gum, a quince seed extract, a tragacanth gum, a guar gum, a starch, a chemically modified starch, a cellulose ether, an alkyl cellulose, a hydroxyalkyl cellulose, a hydroxyethyl cellulose, a hydroxypropyl cellulose, a methyl cellulose, a carboxymethyl cellulose, a methylhydroxyethylcellulose, a methylhydroxypropylcellulose, a hydroxypropylmethyl cellulose, a hydroxyethylcarboxymethylcellulose, a carboxymethylhydroxyethylcellulose, a hydroxypropyl guar gum, a soluble starch, a carboxyvinyl polymer, a polyvinylpyrrolidone, a polyvinyl alcohol, a polyacrylic acid polymer, a polymethacrylic acid polymer, a polyvinyl acetate polymer, a polyvinyl chloride polymer, a polyvinylidene chloride polymer, an acrylic acid/ethyl acrylate copolymer, a carboxyvinyl polymer, a silicone dioxide, a poly(acrylic)acid, a poly(methylvinyl ether/maleic anhydride) copolymer, a chitosan, an alginic acid, a hyaluronic acid, a pectin, a karaya gum, a cyclodextrin, a chemically modified cyclodextrin, hydroxypropyl-β

-cyclodextrin, a poly(N-isopropylamide), a poloxamer, and mixtures of any two or more thereof; and

wherein the composition is provided in an aerosol container and upon release expands to form a breakable foam that collapses upon application of shear force.

2. The composition of claim 1, wherein the surface active agent is 0.1% to 5% by weight of the composition.

3. The composition of claim 1 or 2, wherein the ratio of the hydrophobic organic carrier and the polar solvent are selected to provide a selected pharmacological or safety property.

4. The composition of claim 1, wherein the polymeric agent is 0.01% to 5% by weight of the composition.

5. The composition of claim 1, wherein the polymeric agent is 0.01% to 1% by weight of the composition.

6. The composition of claim 1, further comprising 0.1% to 5% by weight of the composition of a therapeutically active foam adjuvant selected from the group consisting of a fatty alcohol having 15 or more carbons in their carbon chain;

a fatty acid having 16 or more carbons in their carbon chain;

fatty alcohols derived from beeswax and including a mixture of alcohols, a majority of which has at least 20 carbon atoms in their carbon chain;

a fatty alcohol having an double bond;

a fatty acid having an double bond;

a branched fatty alcohol;

a branched fatty acid;

a fatty acid substituted with a hydroxyl group;

cetyl alcohol;

stearyl alcohol;

arachidyl alcohol;

behenyl alcohol;

1-triacontanol;

hexadecanoic acid;

stearic acid;

arachidic acid;

behenic acid;

octacosanoic acid;

12-hydroxy stearic acid; and

a mixture of any two or more thereof.

7. The composition of claim 1, wherein the polar solvent is soluble in both water and oil.

8. The composition of claim 1, wherein the hydrophobic organic carrier is a liquid at ambient temperature, and has a solubility in distilled water at ambient temperature selected from:

(i) less than 1 gm per 100 mL;

(ii) less than 0.5 gm per 100 mL; and

(iii) less than 0.1 gm per 100 mL.

9. The composition of claim 1, wherein the foamable composition is an emulsion or a micro emulsion selected from the group consisting of an oil-in-water emulsion and a water-in-oil emulsion.

10. The composition of claim 1, wherein upon release from the container, a foam having a density range selected from (1) between 0.02 gr/mL and 0.1 gr/mL;

and (2) between 0.04 gr/mL and 0.23 gr/mL is produced.

11. The composition of claim 1, wherein the triglyceride is capric-caprylic triglyceride.

12. The composition of claim 1, further comprising an active agent.

13. The composition of claim 12, wherein the active agent is selected from the group consisting of an anti-infective agent, an antibiotic agent, an antibacterial agent, an antifungal agent, an antiviral agent, an antiparasitic agent, a steroidal anti-inflamatory agent, a nonsteroidal anti-inflammatory agent, an immunosuppressive agent, an immunomodulator, an immunoregulating agent, a hormonal agent, a steroid, a vasoactive agent, a vasoconstructor, a vasodilator, vitamin A, a vitamin A derivative, a retinoid, vitamin B, a vitamin B derivative, vitamin C, a vitamin C derivative, vitamin D, a vitamin D derivative, vitamin E, a vitamin E derivative, vitamin F, a vitamin F derivative, vitamin K, a vitamin K derivative, a wound healing agent, a burn healing agent, an antiallergic agent, a dicarboxylic acid, azelaic acid, sebacic acid, adipic acid, fumaric acid, a retinoid, and a mixture of any two or more thereof at any proportion.

14. The composition of claim 1, further comprising an active agent, selected from the group consisting of a nonsteroidal anti-inflammatory drug, an immunosuppressive agent, an immunomodulator, an immunoregulating agent, a hormonal agent, a steroid, a steroidal anti-inflammatory agent, vitamin A, a vitamin A derivative, vitamin D, a vitamin D derivative, and a mixture of any two or more thereof.

15. The composition of claim 12, wherein the active agent comprises an extract or tincture comprising one or more beneficial agents selected from the group consisting of a hyularonic acid, a herbal extract, coal tar, and a mixture of any two or more thereof.

16. The composition of claim 12, wherein the active agent comprises one or more herbal extracts.

17. The composition of claim 16, wherein the herbal extract is selected from the group consisting of angelica, calendula, celery, coltsfoot, comfrey, dandelion, jamaica dogwood, kava, marshmallow, prickly ash, northern prickly ash, southern senna, valerian, agrimony, aloe vera, alfalfa, artichoke, avens, bayberry, bloodroot, blue flag, bogbean, boldo, boneset, broom, buchu, burdock, burnet, calamus, calendula, cascara, centaury, cereus, chamomile, german chamomile, roman chamomile, cinnamon, divers, cohosh, black, cohosh, blue, cola, corn silk, couchgrass, cowslip, damiana, devil'"'"'s claw, drosera, echinacea, elder, elecampane, euphorbia, eyebright, figwort, frangula, fucus, fumitory, garlic, golden seal, gravel root, ground ivy, guaiacum, hawthorn, holy thistle, hops, horehound black, horehound white, horse chestnut hydrangea, ispaghula, juniper, lady'"'"'s lipper, liferoot, lime flower, liquorice, lobelia, mate, meadowsweet, mistletoe, motherwort, myrrh, nettle, parsley, parsley piert, passionflower, pennyroyal, pilewort, plantain, pleurisy root, pokeroot, poplar, pulsatilla, queen'"'"'s delight, raspberry, red clover, rosemary, sage, sarsaparilla, sassafras, scullcap, senega, shepherd'"'"'s purse, skunk cabbage, slippery elm, squill, St. john'"'"'s wort, stone root, tansy, thyme, uva-ursi, vervain, wild carrot, wild lettuce, willow, witch hazel, yarrow, yellow dock, and a mixture of any two or more thereof.

18. The composition of claim 16, wherein the herbal extract comprises a polar solvent.

19. The composition of claim 12, wherein the active agent is selected from the group consisting of a therapeutically effective amount of a solvent, a surface active agent, a foam adjuvant, a gelling agent, and a mixture of any two or more thereof.

33. A composition of any of claim 1, 12, 13, 14, 15, 16, 17, or 18, further comprising an antibiotic, a coal tar, a dicarboxylic acid, or a steroid.

34. The composition of any of claim 12, 13, 14, 15, 16, 17, or 18, wherein the composition provides increased solubility of the active or beneficial agent.

35. The composition of any of claim 12, 13, 14, 15, 16, 17, or 18, wherein the composition provides increased delivery of the active or beneficial agent.

36. The composition of any of claim 1, 12, 13, 14, 15, 16, 17, or 18, wherein the composition provides enhanced skin barrier build up.

37. The composition of any of claim 12, 13, 14, 15, 16, 17, or 18, wherein the composition provides increased penetration of the active agent.

38. The composition of claim 16, wherein the at least one polar solvent comprises a polar solvent component of the liquid organic carrier and a polar solvent component of the extracts.

39. The composition of claim 13, wherein the polar solvent further comprises propylene glycol;

wherein the triglyceride comprises capric-caprylic triglycerides;

wherein the surface-active agent comprises glyceryl stearate, PEG-40 stearate, polysorbate 80, or any mixtures of two or more thereof;

wherein the polymeric agent comprises a xanthan gum, a methyl cellulose, or mixtures thereof; and

wherein the composition further comprises a foam adjuvant comprising a cetostearyl alcohol.

42. The composition of claim 12, wherein the active agent is azelaic acid.

43. The composition of claim 42, wherein the surface active agent is 0.1% to 5% by weight of the composition.

44. The composition of claim 42, wherein the polymeric agent is 0.01% to 5% by weight of the composition.

45. The composition of claim 42, wherein the polymeric agent is 0.01% to 1% by weight of the composition.

46. The composition of claim 42, further comprising 0.1% to 5% by weight of the composition of a therapeutically active foam adjuvant selected from the group consisting of a fatty alcohol having 15 or more carbons in their carbon chain;

a fatty acid having 16 or more carbons in their carbon chain;

fatty alcohols derived from beeswax and including a mixture of alcohols, a majority of which has at least 20 carbon atoms in their carbon chain;

a fatty alcohol having an double bond;

a fatty acid having an double bond;

a branched fatty alcohol;

a branched fatty acid;

a fatty acid substituted with a hydroxyl group;

cetyl alcohol;

stearyl alcohol;

arachidyl alcohol;

behenyl alcohol;

1-triacontanol;

hexadecanoic acid;

stearic acid;

arachidic acid;

behenic acid;

octacosanoic acid;

12-hydroxy stearic acid; and

a mixture of any two or more thereof.

47. The composition of claim 42, wherein the triglyceride is capric-caprylic triglyceride.

54. The composition of claim 12, wherein the active agent comprises an anti-oxidant, a radical scavenger or mixtures thereof.

55. The composition of claim 54, wherein the composition further comprises a foam adjuvant comprising behenyl alcohol.

58. The composition of claim 12, further comprising a humectant, a film forming agent, or mixtures thereof.

62. The composition of claim 39, wherein the hydrophobic organic carrier is in an amount of about 10% to about 20% by weight of the composition, or about 20% to about 50% by weight of the composition.

63. The composition of claim 39, wherein the ratio between the polar solvent and the hydrophobic organic carrier is selected from the group consisting of between about 1:

4 and about 4;

1, between about 1;

1 and about 4;

1, between about 2;

8 and about 1;

1, about 1;

4, about 1;

2, about 3;

4, about 1;

1, about 5;

4, about 4;

2, about 3;

1, about 4;

1, about 6;

4, and about 7;

4.

64. The composition of claim 62, wherein the surface-active agent is less than about 2% or less than about 1% by weight of the composition.

65. The composition of claim 39, wherein the propylene glycol is about 10% to about 20% by weight of the composition;

wherein the dimethyl isosorbide is about 5% to about 10% by weight of the composition;

wherein the capric-caprylic triglycerides is about 10% to about 20% by weight of the composition;

wherein the surface-active agent comprises about 0.1% to about 5% by weight of the composition of glyceryl stearate, PEG-40 stearate, polysorbate 80, or mixtures of any two or more thereof;

wherein the polymeric agent comprises about 0.01% to about 5% by weight of the composition of a xanthan gum, a methyl cellulose, or mixtures thereof; and

wherein the cetostearyl alcohol is about 0.4% to about 2.5% by weight of the composition.

66. The composition of claim 13, further comprising a humectant, an emollient, or a mixture thereof, wherein the emollient is selected from the group consisting of isopropyl myristate, isopropyl palmitate, isopropyl isostearate, diisopropyl adipate, diisopropyl dimerate, maleated soybean oil, octyl palmitate, cetyl lactate, cetyl ricinoleate, tocopheryl acetate, cetyl acetate, tocopheryl linoleate, wheat germ glycerides, arachidyl propionate, myristyl lactate, decyl oleate, propylene glycol ricinoleate, isopropyl lanolate, pentaerythrityl tetrastearate, neopentylglycol dicaprylate/dicaprate, isononyl isononanoate, isotridecyl isononanoate, myristyl myristate, octyl dodecanol, sucrose esters of fatty acids, octyl hydroxystearate and mixtures of any two or more thereof;

and wherein upon release from a pressurized container, the composition expands to form a foam that collapses upon application of shear force but does not immediately collapse upon exposure to skin temperature.

20. A method of treating or alleviating a disorder selected from the group consisting of acne, an infection, an inflammation, psoriasis, and rosacea, comprising:

administering topically to a surface having the disorder, a foamed composition obtained from a canister comprising a foamable composition comprising;

(1) a liquid organic carrier, at a concentration of 10% to 70% by weight of the foamable composition, wherein said organic carrier concurrently comprises;

i. at least one hydrophobic organic carrier comprising a triglyceride, and

ii. at least one polar solvent comprising dimethyl isosorbide;

(2) 0.1% to 5% by weight of the foamable composition of a surface-active agent selected from the group consisting of at least one non-ionic surface-active agent, and a mixture of a non-ionic surface-active agent and an ionic surface-active agent, wherein the ratio of non-ionic surface-active agent to ionic surface-active agent is greater than 14;

1;

(3) water;

(4) at least one liquefied or compressed gas propellant at a concentration of 3% to 25% by weight of the total composition;

(5) a polymeric agent selected from the group consisting of a locust bean gum, sodium caseinate, an egg albumin, a gelatin agar, a carrageenin gum, sodium alginate, a xanthan gum, a quince seed extract, a tragacanth gum, a guar gum, a starch, a chemically modified starch, a cellulose ether, an alkyl cellulose, a hydroxyalkyl cellulose, a hydroxyethyl cellulose, a hydroxypropyl cellulose, a methyl cellulose, a carboxymethyl cellulose, a methylhydroxyethylcellulose, a methylhydroxypropylcellulose, a hydroxypropylmethyl cellulose, a hydroxyethylcarboxymethylcellulose, a carboxymethylhydroxyethylcellulose, a hydroxypropyl guar gum, a soluble starch, a carboxyvinyl polymer, a polyvinylpyrrolidone, a polyvinyl alcohol, a polyacrylic acid polymer, a polymethacrylic acid polymer, a polyvinyl acetate polymer, a polyvinyl chloride polymer, a polyvinylidene chloride polymer, an acrylic acid/ethyl acrylate copolymer, a carboxyvinyl polymer, a silicone dioxide, a poly(acrylic)acid, a poly(methylvinyl ether/maleic anhydride) copolymer, a chitosan, an alginic acid, a hyaluronic acid, a pectin, a karaya gum, a cyclodextrin, a chemically modified cyclodextrin, hydroxypropyl-β

-cyclodextrin, a poly(N-isopropylamide), a poloxamer, and mixtures of any two or more thereof; and

(6) an active agent; and

wherein the composition is provided in an aerosol container and upon release expands to form a breakable foam that collapses upon application of shear force.

21. The method of claim 20, wherein the composition further includes 0.1% to 5% by weight of the foamable composition of a therapeutically active foam adjuvant is selected from the group consisting of a fatty alcohol having 15 or more carbons in their carbon chain;

a fatty acid having 16 or more carbons in their carbon chain;

fatty alcohols derived from beeswax and including a mixture of alcohols, a majority of which has at least 20 carbon atoms in their carbon chain;

a fatty alcohol having an double bond;

a fatty acid having an double bond;

a branched fatty alcohol;

a branched fatty acid;

a fatty acid substituted with a hydroxyl group;

cetyl alcohol;

stearyl alcohol;

arachidyl alcohol;

behenyl alcohol;

1-triacontanol;

hexadecanoic acid;

stearic acid;

arachidic acid;

behenic acid;

octacosanoic acid;

12-hydroxy stearic acid; and

a mixture of any two or more thereof.

22. The method of claim 20, wherein the concentration of the polymeric agent is 0.01% to 5% by weight of the foamable composition.

23. The method of claim 20, wherein the surface active agent HLB or the weighted average of the HLB values in the composition is about 9 to about 14.

24. The method of claim 20, wherein the active agent is selected from the group consisting of an anti-infective agent, an antibiotic agent, an antibacterial agent, an antifungal agent, an antiviral agent, an antiparasitic agent, a steroid anti-inflammatory agent, a nonsteroidal anti-inflammatory drug, an immunosuppressive agent, an immunomodulator, an immunoregulating agent, a hormonal agent, a steroid, a vasoactive agent, a vasoconstrictor, a vasodilator, vitamin A, a vitamin A derivative, a retinoid, vitamin B, a vitamin B derivative, vitamin C, a vitamin C derivative, vitamin D, a vitamin D derivative, vitamin E, a vitamin E derivative, vitamin F, a vitamin F derivative, vitamin K, a vitamin K derivative, a wound healing agent, a burn healing agent, an antiallergic agent, a dicarboxylic acid, azelaic acid, sebacic acid, adipic acid, fumaric acid, and a mixture of any two or more thereof at any proportion.

25. The method of claim 20, wherein the foamable composition further comprises at least one active agent selected from the group consisting of a non-steroidal anti-inflammatory drug, an immunosuppressive agent, an immunomodulator, an immunoregulating agent, a hormonal agent, a steroid, a steroidal anti-inflammatory agent, vitamin A, a vitamin A derivative, vitamin D, a vitamin D derivative, and a mixture of any two or more thereof.

26. The method of claim 20, wherein the active agent comprises an extract or tincture comprising one or more beneficial agents selected from the group consisting of a hyularonic acid, a herbal extract, coal tar, and a mixture of any two or more thereof.

27. The method of claim 20, wherein the active agent comprises one or more herbal extracts.

28. The method of claim 27, wherein the herbal extract is selected from the group consisting of angelica, calendula, celery, coltsfoot, comfrey, dandelion, jamaica dogwood, kava, marshmallow, prickly ash, northern prickly ash, southern senna, valerian, agrimony, aloe vera, alfalfa, artichoke, avens, bayberry, bloodroot, blue flag, bogbean, boldo, boneset, broom, buchu, burdock, burnet, calamus, calendula, cascara, centaury, cereus, chamomile, german chamomile, roman chamomile, cinnamon, divers, cohosh, black, cohosh, blue, cola, corn silk, couchgrass, cowslip, damiana, devil'"'"'s claw, drosera, echinacea, elder, elecampane, euphorbia, eyebright, figwort, frangula, fucus, fumitory, garlic, golden seal, gravel root, ground ivy, guaiacum, hawthorn, holy thistle, hops, horehound black, horehound white, horse chestnut hydrangea, ispaghula, juniper, lady'"'"'s lipper, liferoot, lime flower, liquorice, lobelia, mate, meadowsweet, mistletoe, motherwort, myrrh, nettle, parsley, parsley piert, passionflower, pennyroyal, pilewort, plantain, pleurisy root, pokeroot, poplar, pulsatilla, queen'"'"'s delight, raspberry, red clover, rosemary, sage, sarsaparilla, sassafras, scullcap, senega, shepherd'"'"'s purse, skunk cabbage, slippery elm, squill, St. john'"'"'s wort, stone root, tansy, thyme, uva-ursi, vervain, wild carrot, wild lettuce, willow, witch hazel, yarrow, yellow dock, and a mixture of any two or more thereof.

29. The method of claim 27, wherein the herbal extract comprises a polar solvent.

41. The method of claim 24, wherein the polar solvent further comprises propylene glycol;

wherein the triglyceride comprises capric-caprylic triglycerides;

wherein the surface-active agent comprises glyceryl stearate, PEG-40 stearate, polysorbate 80, or any mixtures of two or more thereof;

wherein the polymeric agent comprises a xanthan gum, a methyl cellulose, or mixtures thereof; and

wherein the composition further comprises a foam adjuvant comprising a cetostearyl alcohol.

48. The method of claim 20, wherein the active agent is azelaic acid.

49. The method of claim 48, wherein the surface active agent is 0.1% to 5% by weight of the composition.

50. The method of claim 48, wherein the polymeric agent is 0.01% to 5% by weight of the composition.

51. The method of claim 48, wherein the polymeric agent is 0.01% to 1% by weight of the composition.

52. The method of claim 48, further comprising 0.1% to 5% by weight of the composition of a therapeutically active foam adjuvant selected from the group consisting of a fatty alcohol having 15 or more carbons in their carbon chain;

a fatty acid having 16 or more carbons in their carbon chain;

fatty alcohols derived from beeswax and including a mixture of alcohols, a majority of which has at least 20 carbon atoms in their carbon chain;

a fatty alcohol having an double bond;

a fatty acid having an double bond;

a branched fatty alcohol;

a branched fatty acid;

a fatty acid substituted with a hydroxyl group;

cetyl alcohol;

stearyl alcohol;

arachidyl alcohol;

behenyl alcohol;

1-triacontanol;

hexadecanoic acid;

stearic acid;

arachidic acid;

behenic acid;

octacosanoic acid;

12-hydroxy stearic acid; and

a mixture of any two or more thereof.

53. The method of claim 48, wherein the triglyceride is capric-caprylic triglyceride.

56. The method of claim 20, wherein the active agent comprises an anti-oxidant, a radical scavenger, or mixtures thereof.

57. The method of claim 56, wherein the composition further comprises a foam adjuvant comprising behenyl alcohol.

67. The method of claim 27, wherein the at least one polar solvent comprises a polar solvent component of the liquid organic carrier and a polar solvent component of the extracts.

30. A non-flammable foamable pharmaceutical composition comprising:

(1) a liquid organic carrier, at a concentration of 10% to 70% by weight of the pharmaceutical composition, wherein said organic carrier contains at least one member selected from the group consisting of;

(i) at least one hydrophobic organic carrier comprising a triglyceride, and

(ii) at least one polar solvent comprising dimethyl isosorbide and a diol;

(2) a surface-active agent selected from the group consisting of at least one non-ionic surface-active agent, and a mixture of a non-ionic surface-active agent and an ionic surface-active agent, wherein the ratio of non-ionic surface-active agent to ionic surface-active agent is greater than 14;

1;

(3) water;

(4) at least one hydrofluorocarbon propellant at a concentration of 3% to 25% by weight of the total composition; and

(5) a polymeric agent selected from the group consisting of a locust bean gum, sodium caseinate, an egg albumin, a gelatin agar, a carrageenin gum, sodium alginate, a xanthan gum, a quince seed extract, a tragacanth gum, a guar gum, a starch, a chemically modified starch, a cellulose ether, an alkyl cellulose, a hydroxyalkyl cellulose, a hydroxyethyl cellulose, a hydroxypropyl cellulose, a methyl cellulose, a carboxymethyl cellulose, a methylhydroxyethylcellulose, a methylhydroxypropylcellulose, a hydroxypropylmethyl cellulose, a hydroxyethylcarboxymethylcellulose, a carboxymethylhydroxyethylcellulose, a hydroxypropyl guar gum, a soluble starch, a carboxyvinyl polymer, a polyvinylpyrrolidone, a polyvinyl alcohol, a polyacrylic acid polymer, a polymethacrylic acid polymer, a polyvinyl acetate polymer, a polyvinyl chloride polymer, a polyvinylidene chloride polymer, an acrylic acid/ethyl acrylate copolymer, a carboxyvinyl polymer, a silicone dioxide, a poly(acrylic)acid, a poly(methylvinyl ether/maleic anhydride) copolymer, a chitosan, an alginic acid, a hyaluronic acid, a pectin, a karaya gum, a cyclodextrin, a chemically modified cyclodextrin, hydroxypropyl-β

-cyclodextrin, a poly(N-isopropylamide), a poloxamer, and mixtures of any two or more thereof; and

wherein the composition is provided in an aerosol container and upon release expands to form a breakable foam that collapses upon application of shear force.

31. The composition of claim 30, further comprising 0.1% to 5% by weight of the pharmaceutical composition of a therapeutically active foam adjuvant is selected from the group consisting of a fatty alcohol having 15 or more carbons in their carbon chain;

a fatty acid having 16 or more carbons in their carbon chain;

fatty alcohols derived from beeswax and including a mixture of alcohols, a majority of which has at least 20 carbon atoms in their carbon chain;

a fatty alcohol having an double bond;

a fatty acid having an double bond;

a branched fatty alcohol;

a branched fatty acid;

a fatty acid substituted with a hydroxyl group;

cetyl alcohol;

stearyl alcohol;

arachidyl alcohol;

behenyl alcohol;

1-triacontanol;

hexadecanoic acid;

stearic acid;

arachidic acid;

behenic acid;

octacosanoic acid;

12-hydroxy stearic acid; and

a mixture of any two or more thereof.

32. The composition of claim 31, wherein the concentration of the polymeric agent is 0.01% to 5% by weight of the pharmaceutical composition.

40. The composition of claim 30, wherein the polar solvent further comprises propylene glycol;

wherein the triglyceride comprises capric-caprylic triglycerides;

wherein the surface-active agent comprises glyceryl stearate, PEG-40 stearate, polysorbate 80, or any mixtures of two or more thereof;

wherein the polymeric agent comprises a xanthan gum, a methyl cellulose, or mixtures thereof; and

wherein the composition further comprises a foam adjuvant comprising a cetostearyl alcohol.

59. The composition of claim 40, further comprising an active agent.

60. The composition of claim 59, wherein the propylene glycol is about 10% to about 20% by weight of the composition;

wherein the dimethyl isosorbide is about 5% to about 10% by weight of the composition;

wherein the capric-caprylic triglycerides is about 10% to about 20% by weight of the composition;

wherein the surface-active agent comprises about 0.1% to about 5% by weight of the composition of glyceryl stearate, PEG-40 stearate, polysorbate 80, or mixtures of any two or more thereof;

wherein the polymeric agent comprises about 0.01% to about 5% by weight of the composition of a xanthan gum, a methyl cellulose, or mixtures thereof; and

wherein the cetostearyl alcohol is about 0.4% to about 2.5% by weight of the composition.

61. The composition of claim 60, further comprising a humectant, a film forming agent, or mixtures thereof.