Foamable vehicle and pharmaceutical compositions thereof

• US 9,636,405 B2
• Filed: 03/11/2013
• Issued: 05/02/2017
• Est. Priority Date: 08/04/2003
• 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): Arnold, Ernst V
• Application Number:
  US13/793,893
• Publication Number:
  US 20130189193A1
• Time in Patent Office: 1,513 Days
• 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 less than 0.9 or about 0.9 to about 0.7 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 foamable pharmaceutical composition in a container comprising:

i) a carrier composition comprising;

a) at least one polar solvent selected from the group consisting of;

a polyethylene glycol (PEG) and a polyol, wherein the polar solvent is at a sufficient concentration to provide an Aw value of the pharmaceutical composition of less than 0.9 or about 0.9 to about 0.7;

b) a foam adjuvant;

c) a hydrophobic solvent comprising an oil selected from the group consisting of a mineral oil, isopropyl palmitate, isopropyl isostearate, diisopropyl adipate, diisopropyl dimerate, a 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, propylene glycol ricinoleate, isopropyl lanolate, pentaerythrityl tetrastearate, neopentylglycol dicaprylate/dicaprate, isononyl isononanoate, isotridecyl isononanoate, myristyl myristate, triisocetyl citrate, octyl dodecanol, an olive oil, a canola oil, a cottonseed oil, a coconut oil, a sesame oil, a sunflower oil, a borage seed oil, a syzigium aromaticum oil, a hempseed oil, a herring oil, a cod-liver oil, a salmon oil, a flaxseed oil, a wheat germ oil, an evening primrose oils, an essential oil and mixtures of any two or more thereof; and

d) water; and

ii) a liquefied or compressed gas propellant;

wherein the composition does not contain a gelling agent;

wherein the composition comprises less than 5% by weight of the carrier composition of a short chain alcohol; and

wherein the foamable pharmaceutical composition forms a uniform foam upon release from the container.

2. The pharmaceutical composition of claim 1, further comprising one or more active agents, and 0% to about 5% by weight of the carrier composition of a surface-active agent;

wherein the foam adjuvant is between about 1% to about 10% by weight of the carrier composition.

18. The pharmaceutical composition of claim 2, further comprising a secondary polar solvent comprising dimethylisosorbide, wherein the ratio between the polyol and/or PEG and the secondary polar solvent is between 9:

1 and 1;

1.

19. The pharmaceutical composition of claim 2, further comprising a secondary polar solvent comprising dimethylisosorbide, wherein the secondary polar solvent is between 14.25% and 59.5% by weight of carrier.

20. The pharmaceutical composition of claim 1, wherein the foam adjuvant comprises a fatty acid.

22. The pharmaceutical composition of claim 1, wherein the foamable pharmaceutical composition forms a breakable foam upon dispensing from the pressurized container.

24. A method of treating a disorder in a mammalian subject comprising administering to the subject the foamable therapeutic composition of claim 2 to a target area 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, wherein the one or more active agents comprise an anti-infective agent, 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.

3. A foamable pharmaceutical carrier composition in a container comprising:

i) a carrier composition comprising;

a) about 50% to about 98% by weight of the carrier composition of a primary polar solvent and a secondary polar solvent, wherein the primary polar solvent is selected from the group consisting of (1) a polyol and (2) a polyethylene glycol (PEG);

b) a foam adjuvant;

c) a hydrophobic solvent comprising an oil selected from the group consisting of a mineral oil, isopropyl palmitate, isopropyl isostearate, diisopropyl adipate, diisopropyl dimerate, a 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, propylene glycol ricinoleate, isopropyl lanolate, pentaerythrityl tetrastearate, neopentylglycol dicaprylate/dicaprate, isononyl isononanoate, isotridecyl isononanoate, myristyl myristate, triisocetyl citrate, octyl dodecanol, an olive oil, a canola oil, a cottonseed oil, a coconut oil, a sesame oil, a sunflower oil, a borage seed oil, a syzigium aromaticum oil, a hempseed oil, a herring oil, a cod-liver oil, a salmon oil, a flaxseed oil, a wheat germ oil, an evening primrose oils, an essential oil and mixtures of any two or more thereof; and

d) water; and

ii) a liquefied or compressed gas propellant;

wherein the composition does not contain a gelling agent;

wherein the composition comprises less than 5% by weight of the carrier composition of a short chain alcohol; and

wherein the foamable pharmaceutical carrier composition forms a uniform foam upon dispensing from the container.

4. The pharmaceutical composition of claim 3, wherein the foam adjuvant is between about 1% to about 10% by weight of the carrier composition, and wherein the foam adjuvant is selected from the group consisting of a fatty alcohol, a fatty acid, a hydroxyl fatty acid, a branched fatty alcohol or fatty acid, and a mixture of any two or more thereof.

5. The pharmaceutical composition of claim 4, wherein the fatty alcohol is selected from a group consisting of a oleyl alcohol, stearyl alcohol, cetyl alcohol, cetostearyl alcohol, arachidyl alcohol, behenyl alcohol, 1-triacontanol, a fatty alcohol with a carbon chain having 15 to 50 carbon atoms, a fatty alcohol derived from beeswax, or mixtures of any two or more thereof;

wherein the fatty acid is selected from a group consisting of hexadecanoic acid, stearic acid, arachidic acid, behenic acid, octacosanoic acid, a hydroxyl fatty acid, a fatty acid with a carbon chain having 16 to 50 carbon atoms, or mixtures of any two or more thereof; and

wherein the hydroxyl fatty acid comprises 12-hydroxy stearic acid.

6. The pharmaceutical composition of claim 3, wherein the polar solvent is a PEG selected from the group consisting of PEG 200, PEG 300, PEG 400, PEG 600, PEG 1000, PEG 4000, PEG 6000, PEG 8000, and mixtures of any two or more thereof.

7. The pharmaceutical composition of claim 3, wherein the composition does not contain a surface-active agent.

8. The pharmaceutical composition of claim 4, further comprising one or more active agents.

9. The pharmaceutical composition of claim 3, wherein the polyol comprises at least one of glycerin, butane-1,2,3-triol, butane-1,2,4-triol, hexane-1,2,6-triol, 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, or a mixture of at least two polyols.

10. The pharmaceutical composition of claim 3, wherein the polar solvent comprises a mixture of at least one polyol and at least one PEG.

11. The pharmaceutical composition of claim 8, further comprising about 0.2% to about 5% by weight of the carrier composition of a surface-active agent, wherein the surface-active agent comprises a non-ionic surfactant.

12. The pharmaceutical composition of claim 11, wherein the surface-active agent comprises at least one non-ionic surfactant and at least one ionic surfactant, wherein the ratio of non-ionic surfactant to ionic surfactant is in the range of about 100:

1 to about 6;

1.

13. The pharmaceutical composition of claim 8, further comprising a hygroscopic substance selected from the group consisting of monosaccharides, disaccharides, oligosaccharides, sugar alcohols, honey, a PEG containing surfactant, and a mixture of any two or more thereof, wherein the composition can provide an Aw value of less than 0.9 or about 0.9 to about 0.7.

14. The pharmaceutical composition of claim 13, further comprising one or more of a penetration enhancer, a buffer, a preservative and a humectant.

15. The pharmaceutical composition of claim 5, wherein the foam adjuvant comprises stearyl alcohol.

16. The pharmaceutical composition of claim 8, comprising a secondary polar solvent comprising dimethylisosorbide, wherein the ratio between the polyol and/or PEG and the secondary polar solvent is between 9:

1 and 1;

1.

17. The pharmaceutical composition of claim 8, comprising a secondary polar solvent comprising at least 14.25% by weight of carrier of dimethylisosorbide.

21. The pharmaceutical composition of claim 3, wherein the foam adjuvant comprises a fatty acid.

23. The pharmaceutical composition of claim 3, wherein the foamable pharmaceutical composition forms a breakable foam upon dispensing from the pressurized container.

25. A method of treating a disorder in a mammalian subject comprising administering to the subject the foamable therapeutic composition of claim 9 to a target area 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, wherein the one or more active agents comprise an anti-infective agent, 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.