Stable Dermatological Aerosol Foams Utilizing Reactive Propellants

• US 20130115173A1
• Filed: 11/02/2012
• Published: 05/09/2013
• Est. Priority Date: 11/03/2011
• Status: Abandoned Application

• Current Assignee: PreCision Dermatology, Inc. (Bausch Health Cos., Inc.)
• Original Assignee: PreCision Dermatology, Inc. (Bausch Health Cos., Inc.)
• Inventors: Trumbore, Mark W., Majhi, Pinaki Ranjan
• Application Number:
  US13/667,209
• Publication Number:
  US 20130115173A1
• Time in Patent Office: Days
• US Class Current: 424/45
• 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: A61K 9/124 characterised by the propellant
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders

Abstract

Described herein are chemically-stabile formulations comprising a reactive propellant. The formulations are delivered as an aerosol foam, and are suitable for topical application. The aerosol propellant may be a hydrofluoroolefin propellant. The emulsions or compositions may comprise reactive active agents, such as peroxides, retinoids, or quinones. Also described are methods of treating skin disorders, comprising the step of applying to an affected area of a subject in need thereof a therapeutically-effective amount of an inventive emulsion or aerosol composition.

Claims

1. A composition, comprising:

an emulsion;

a propellant; and

a purge gas,

wherein

the emulsion comprises;

water,

an emulsifier or surfactant,

a moisturizer or emollient,

an antioxidant or preservative, and

an active agent; and

the propellant is selected from the group consisting of Z-1,2,3,3,3-pentafluoropropene, E-1,2,3,3,3-pentafluoropropene, 1,1,3,3,3-pentafluoropropene, 1,1,2,3,3-pentafluoropropene, 2,3,3,3-tetrafluoropropene, trans-1,3,3,3-tetrafluoroprop-1-ene, cis-1,3,3,3-tetrafluoropropene, and 3,3,3-trifluoropropene, and combinations/mixtures thereof.

2. The composition of claim 1, wherein the emulsion further comprises a pH adjuster.

3. The composition of claim 1, wherein the emulsion further comprises a buffer.

4. The composition of claim 1, wherein the emulsion comprises:

water, from about 24% to about 90% by weight of the emulsion;

sodium hyaluronate, from about 0.05% to about 1.5% by weight of the emulsion;

glycerin, from about 2.5% to about 10% by weight of the emulsion;

ethylhexyl palmitate, from about 3% to about 9% by weight of the emulsion;

cetostearyl alcohol, from about 0.5% to about 5% by weight of the emulsion;

dicetyl phosphate, from about 1% to about 3% by weight of the emulsion;

ceteth-10 phosphate, from about 0.5% to about 1.5% by weight of the emulsion;

propylene glycol, from about 1% to about 4% by weight of the emulsion;

theobroma grandiflorum seed butter, from about 1% to about 3% by weight of the emulsion;

dimethicone, from about 0.2% to about 2% by weight of the emulsion;

petrolatum, from about 0.5% to about 6% by weight of the emulsion;

polyethylene glycol octadecyl ether, from about 0.2% to about 3% by weight of the emulsion;

tocopheryl acetate, from about 0.2% to about 0.8% by weight of the emulsion;

1,3-bis(N-2-(hydroxyethyl)palmitoylamino)-2-hydroxypropane, from about 0.2% to about 0.8% by weight of the emulsion;

methylparaben, from about 0.01% to about 0.5% by weight of the emulsion;

sodium hydroxide, from about 0.01% to about 0.3% by weight of the emulsion;

propylparaben, from about 0.05% to about 0.2% by weight of the emulsion; and

disodium EDTA, from about 0.05% to about 0.2% by weight of the emulsion.

5. The composition of claim 1, wherein the emulsion comprises:

water, from about 24% to about 90% by weight of the emulsion;

benzoyl peroxide, from about 0.05% to about 15% by weight of the emulsion;

glycerin, from about 2.5% to about 10% by weight of the emulsion;

propylene glycol, from about 1% to about 4% by weight of the emulsion;

cetostearyl alcohol, from about 0.5% to about 5% by weight of the emulsion;

emulsifying wax, from about 0.5% to about 5% by weight of the emulsion;

dimethicone, from about 0.2% to about 2% by weight of the emulsion;

sodium citrate, from about 0.3% to about 0.9% by weight of the emulsion;

Polyethylene glycol octadecyl ether, from about 0.2% to about 3% by weight of the emulsion;

methylparaben, from about 0.01% to about 0.5% by weight of the emulsion;

C₁₂-C₁₅ alkyl benzoates, from about 0.1% to about 0.3% by weight of the emulsion;

propylparaben, from about 0.05% to about 0.2% by weight of the emulsion;

disodium EDTA, from about 0.05% to about 0.2% by weight of the emulsion;

butylated hydroxytoluene, from about 0.01% to about 0.08% by weight of the emulsion; and

citric acid, from about 0.02% to about 0.08% by weight of the emulsion.

6. The composition of claim 1, wherein the emulsion comprises:

water, from about 24% to about 90% by weight of the emulsion;

oleic acid, from about 1.5% to about 14% by weight of the emulsion;

glycerin, from about 2.5% to about 10% by weight of the emulsion;

alfa terpineol, from about 1.5% to about 4.5% by weight of the emulsion;

pentylene glycol, from about 1% to about 4% by weight of the emulsion;

cetostearyl alcohol, from about 0.5% to about 5% by weight of the emulsion;

emulsifying wax, from about 0.5% to about 5% by weight of the emulsion;

sodium phosphate monobasic, from about 0.5% to about 1.5% by weight of the emulsion;

Polyethylene glycol octadecyl ether, from about 0.2% to about 3% by weight of the emulsion;

Poloxamer 188, from about 0.01% to about 2% by weight of the emulsion;

methylparaben, from about 0.01% to about 0.5% by weight of the emulsion;

sodium hydroxide, from about 0.01% to about 0.3% by weight of the emulsion;

propylparaben, from about 0.05% to about 0.2% by weight of the emulsion;

disodium EDTA, from about 0.05% to about 0.2% by weight of the emulsion;

butylated hydroxytoluene, from about 0.01% to about 0.08% by weight of the emulsion; and

tretinoin, from about 0.05% to about 1% by weight of the emulsion.

7. The composition of claim 1, wherein the emulsion comprises:

water, from about 24% to about 90% by weight of the emulsion;

oleic acid, from about 1.5% to about 14% by weight of the emulsion;

diethyl sebacate, from about 2% to about 12% by weight of the emulsion;

glycerin, from about 2.5% to about 10% by weight of the emulsion;

pentylene glycol, from about 1% to about 4% by weight of the emulsion;

cetostearyl alcohol, from about 0.5% to about 5% by weight of the emulsion;

emulsifying wax, from about 0.5% to about 5% by weight of the emulsion;

sodium phosphate monobasic, from about 0.5% to about 1.5% by weight of the emulsion;

Polyethylene glycol octadecyl ether, from about 0.2% to about 3% by weight of the emulsion;

Poloxamer 188, from about 0.01% to about 2% by weight of the emulsion;

methylparaben, from about 0.01% to about 0.5% by weight of the emulsion;

sodium hydroxide, from about 0.01% to about 0.3% by weight of the emulsion;

propylparaben, from about 0.05% to about 0.2% by weight of the emulsion;

disodium EDTA, from about 0.05% to about 0.2% by weight of the emulsion;

butylated hydroxytoluene, from about 0.01% to about 0.08% by weight of the emulsion; and

tretinoin, from about 0.05% to about 1% by weight of the emulsion.

8. The composition of claim 1, wherein the emulsion comprises:

water, from about 24% to about 90% by weight of the emulsion;

oleic acid, from about 1.5% to about 14% by weight of the emulsion;

diethyl sebacate, from about 2% to about 12% by weight of the emulsion;

glycerin, from about 2.5% to about 10% by weight of the emulsion;

pentylene glycol, from about 1% to about 4% by weight of the emulsion;

cetostearyl alcohol, from about 0.5% to about 5% by weight of the emulsion;

emulsifying wax, from about 0.5% to about 5% by weight of the emulsion;

petrolatum, from about 0.5% to about 6% by weight of the emulsion;

Ceteth-20, from about 3% to about 9% by weight of the emulsion;

sodium phosphate monobasic, from about 0.5% to about 1.5% by weight of the emulsion;

Poloxamer 188, from about 0.01% to about 2% by weight of the emulsion;

methylparaben, from about 0.01% to about 0.5% by weight of the emulsion;

sodium hydroxide, from about 0.01% to about 0.3% by weight of the emulsion;

propylparaben, from about 0.05% to about 0.2% by weight of the emulsion;

disodium EDTA, from about 0.05% to about 0.2% by weight of the emulsion;

butylated hydroxytoluene, from about 0.01% to about 0.08% by weight of the emulsion; and

tretinoin, from about 0.05% to about 1% by weight of the emulsion.

9. The composition of claim 1, wherein the emulsion comprises:

water, from about 24% to about 90% by weight of the emulsion;

diethyl sebacate, from about 2% to about 12% by weight of the emulsion;

glycerin, from about 2.5% to about 10% by weight of the emulsion;

isostearyl alcohol, from about 2% to about 6% by weight of the emulsion;

pentylene glycol, from about 1% to about 4% by weight of the emulsion;

cetostearyl alcohol, from about 0.5% to about 5% by weight of the emulsion;

emulsifying wax, from about 0.5% to about 5% by weight of the emulsion;

petrolatum, from about 0.5% to about 6% by weight of the emulsion;

sodium phosphate monobasic, from about 0.5% to about 1.5% by weight of the emulsion;

Poloxamer 188, from about 0.01% to about 2% by weight of the emulsion;

methylparaben, from about 0.01% to about 0.5% by weight of the emulsion;

sodium hydroxide, from about 0.01% to about 0.3% by weight of the emulsion;

propylparaben, from about 0.05% to about 0.2% by weight of the emulsion;

disodium EDTA, from about 0.05% to about 0.2% by weight of the emulsion;

butylated hydroxytoluene, from about 0.01% to about 0.08% by weight of the emulsion; and

tretinoin, from about 0.05% to about 1% by weight of the emulsion.

10. The composition of claim 1, wherein the emulsifier or surfactant is selected from the group consisting of:

polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, steareth-10, sodium dodecyl sulfate, lauryl dimethyl amine oxide, cetyltrimethylammonium bromide, polyethoxylated alcohols, polyoxyethylene sorbitan, octoxynol, N,N-dimethyldodecylamine-N-oxide, hexadecyltrimethylammonium bromide, polyoxyl 10 lauryl ether, sodium deoxycholate, sodium cholate, polyoxyl castor oil, nonylphenol ethoxylate, cyclodextrins, lecithin, dimethicone copolyol, lauramide DEA, cocamide DEA, cocamide MEA, oleyl betaine, cocamidopropyl betaine, cocamidopropyl phosphatidyl PG-dimonium chloride, dicetyl phosphate, ceteareth-10 phosphate, methylbenzethonium chloride, behentrimonium methosulfate-cetearyl alcohol, non-ionic emulsifiers like emulsifying wax, polyoxyethylene oleyl ether, PEG-40 stearate, ceteareth-12, ceteareth-20, ceteareth-30, ceteareth alcohol, Ceteth-20, oleic acid, oleyl alcohol, glyceryl stearate, PEG-100 stearate, glyceryl stearate and PEG-100 stearate, steareth-2, steareth-20, stearic acid, cholesterol, ceramide 2, ceramide 3, stearamidopropyl dimethylamine, behentrimonium methosulfate, cetostearyl alcohol, dicetyl phosphate, ceteth-10 phosphate, polyethylene glycol octadecyl ether, Poloxamer 188, and combinations/mixtures thereof.

11. The composition of claim 1, wherein the emulsifier or surfactant is present in an amount from about 1% to about 25% by weight of the emulsion.

12. The composition of claim 1, wherein the moisturizer or emollient is selected from the group consisting of petrolatum, glycerol (glycerin), sodium hyaluronate, 2-ethylhexyl palmitate, dimethicone, C₁₂-C₁₅ alkyl benzoates, propylene glycol, Theobroma grandiflorum seed butter, diethyl sebacate, isostearyl alcohol, pentylene glycol, 1,3-bis(N-2-(hydroxyethyl)palmitoylamino)-2-hydroxypropane, and combinations/mixtures thereof.

13. The composition of claim 1, wherein the moisturizer or emollient is present in an amount from about 4% to about 30% by weight of the emulsion.

14. The composition of claim 1, wherein the antioxidant or preservative is selected from the group consisting of imidazolidinyl urea, diazolidinyl urea, phenoxyethanol, sodium methyl paraben, methylparaben, ethylparaben, propylparaben, potassium sorbate, sodium benzoate, sorbic acid, benzoic acid, formaldehyde, citric acid, sodium citrate, chlorine dioxide, benzalkonium chloride, benzethonium chloride, cetrimide, dequalinium chloride, cetylpyridinium chloride, phenylmercuric nitrate, phenylmercuric acetate, thimerosal, piroctone olamine, Vitis vinifera seed oil, chlorobutanol, dichlorobenzyl alcohol, phenylethyl alcohol, benzyl alcohol, ascorbic acid, sodium bisulfite, butylated hydroxytoluene, butylated hydroxyanisole, α

-tocopherol, tocopheryl acetate, sodium ascorbate/ascorbic acid, ascorbyl palmitate, propyl gallate, disodium EDTA, citric acid, and sodium citrate, and combinations/mixtures thereof.

15. The composition of claim 1, wherein the antioxidant or preservative is present in an amount from about 0.25% to about 2% by weight of the emulsion.

16. The composition of claim 1, wherein water is present in an amount about 24% to about 90% by weight of the emulsion.

17. The composition of claim 1, wherein the active agent is present in an amount from about 0.001% to about 15% by weight of the emulsion.

18. The composition of claim 1, wherein the active agent is a retinoid.

19. The composition of claim 1, wherein the active agent is a peroxide.

20. The composition of claim 1, wherein the active agent is selected from the group consisting of benzoyl peroxide, alfa terpineol, octopirox, erythromycin, zinc, tetracyclin, triclosan, azelaic acid and its derivatives, phenoxy ethanol and phenoxy propanol, ethyl acetate, clindamycin and meclocycline, sebostats, alpha and beta hydroxy acids, and bile salts.

21. The composition of claim 1, wherein the active agent is a vitamin.

22. The composition of claim 1, wherein the active agent is a quinone.

23. A method of treating a skin disorder, comprising the step of applying to an affected area of a subject in need thereof a therapeutically-effective amount of a composition of claim 1.