Formulations for treating skin disorders

Abstract

The present invention is drawn to adhesive solidifying formulations for treating skin disorders, such as dermatitis or psoriasis. The formulation can include a drug, a solvent vehicle, and a solidifying agent. The solvent vehicle can include a volatile solvent system including at least one volatile solvent, and a non-volatile solvent system including at least one non-volatile solvent, wherein the non-volatile solvent system is capable of facilitating the delivery of the drug at therapeutically effective rates over a sustained period of time. The formulation can have a viscosity suitable for application to a skin surface prior to evaporation of the volatile solvents system. When applied to the skin, the formulation can form a solidified layer after at least a portion of the volatile solvent system is evaporated.

1 . A formulation for treating skin disorders, comprising:
 a) a corticosteroid selected from the group consisting of betamethasone dipropionate, clobetasol propionate, halobetasol propionate, diflorasone diacetate, amcinonide, desoximethasone, fluocinonide, halcinonide, mometasone furoate, betamethasone valerate, fluticasone propionate, triamcinolone acetonide, fluocinolone acetonide, flurandrenolide, desonide, hydrocortisone butyrate, hydrocortisone valerate, alclometasone dipropionate, flumethasone pivolate, hydrocortisone, hydrocortisone acetate, tacrolimus picrolimus, cholecalciferol, calcitriol, calcipotriol, tacalcitol, tazarotene, and combinations thereof;   b) a solvent vehicle, comprising:
 i) a volatile solvent system, and 
 ii) a non-volatile solvent system, wherein the non-volatile solvent system includes a member selected from the group consisting of propylene glycol, glycerol, isostearic acid, oleic acid, oleyl alcohol, trolamine, tromethamine, triacetin, sorbitan monolaurate, sorbitan monooleate, sorbitan monopalmitate, benzoic acid, dibutyl sebecate, glycerides, dipropylene glycol, eugenol, fatty acids, isopropyl myristate, mineral oil, oleyl alcohol, vitamin E, triglycerides, sorbitan fatty acid surfactants, triethyl citrate, and combinations thereof, 
   wherein the non-volatile solvent system facilitates the delivery of the corticosteroid at therapeutically effective rates; and   c) a solidifying agent;   wherein the formulation has a viscosity suitable for application and adhesion to a skin surface prior to evaporation of the volatile solvent system, the formulation upon being applied to a skin surface as a layer forms a solidified layer after at least partial evaporation of the volatile solvent system, and the corticosteroid is dermally deliverable at the therapeutically effective rate after the volatile solvent system is substantially evaporated.   
     
     
         2 . A formulation as in  claim 1 , wherein the non-volatile solvent system is capable of facilitating delivery of the corticosteroid at therapeutically effective rates over a sustained period of time. 
     
     
         3 . A formulation as in  claim 1 , wherein the solidified layer is capable of adhering to the palm skin of human hands. 
     
     
         4 . A formulation as in  claim 1 , wherein the non-volatile solvent system acts as a plasticizer for the solidifying agent. 
     
     
         5 . A formulation as in  claim 1 , wherein the formulation further comprises an additional agent added to increase adhesion of the formulation when applied to a body surface. 
     
     
         6 . A formulation as in  claim 5 , wherein the additional agent includes at least one member selected from the group consisting of copolymers of methylvinyl ether and maleic anhydride, polyethylene glycol and polyvinyl pyrrolidone, gelatin, low molecular weight polyisobutylene rubber, copolymer of acrylsan alkyl/octylacrylamido, aliphatic resins, aromatic resins, and combinations thereof. 
     
     
         7 . A formulation as in  claim 1 , wherein the weight percentage of the volatile solvent system in the formulation is from about 10 wt % to about 85 wt %. 
     
     
         8 . A formulation as in  claim 1 , wherein the weight percentage of the volatile solvent system in the formulation is from about 20 wt % to about 50 wt %. 
     
     
         9 . A formulation as in  claim 1 , wherein the weight ratio of the non-volatile solvent system to the solidifying agent is from about 0.5:1 to about 2:1. 
     
     
         10 . A formulation as in  claim 1 , wherein the volatile solvent system comprises at least one solvent selected from the group consisting of ethanol, isopropyl alcohol, water, dimethyl ether, diethyl ether, butane, propane, isobutene, 1,1-difluoroethane, 1,1,1,2-tetrafluorethane, 1,1,1,2,3,3,3-heptafluoropropane, 1,1,1,3,3,3-hexafluoropropane, ethyl acetate, acetone, and combinations thereof. 
     
     
         11 . A formulation as in  claim 1 , wherein the volatile solvent system includes at least one solvent more volatile than water selected from the group consisting of denatured alcohol, ethanol, methanol, propanol, isobutene, pentane, hexane, methyl ethyl ketone, and combinations thereof. 
     
     
         12 . (canceled) 
     
     
         13 . (canceled) 
     
     
         14 . A formulation as in  claim 1 , wherein the non-volatile solvent system includes at least one additional member selected from the group consisting of 1,2,6-hexanetriol, alkyltriols, alkyldiols, tocopherol, p-propenylanisole, anise oil, apricot oil, dimethyl isosorbide, alkyl glucoside, benzyl alcohol, bees wax, benzyl benzoate, butylene glycol, caprylic/capric triglyceride, caramel, cassia oil, castor oil, cinnamaldehyde, cinnamon oil, clove oil, coconut oil, cocoa butter, cocoglycerides, coriander oil, corn oil, corn syrup, cottonseed oil, cresol, diacetin, diacetylated monoglycerides, diethanolamine, diglycerides, ethylene glycol, eucalyptus oil, fat, fatty alcohols, flavors, liquid sugars, ginger extract, glycerin, high fructose corn syrup, hydrogenated castor oil, IP palmitate, lemon oil, lime oil, limonene, monoacetin, monoglycerides, nutmeg oil, octyldodecanol, orange oil, palm oil, peanut oil, PEG vegetable oil, peppermint oil, petrolatum, phenol, pine needle oil, polypropylene glycol, sesame oil, spearmint oil, soybean oil, vegetable oil, vegetable shortening, wax, 2-(2-(octadecyloxy)ethoxy)ethanol, benzyl benzoate, butylated hydroxyanisole, candelilla wax, carnauba wax, ceteareth-20, cetyl alcohol, polyglyceryl, dipolyhydroxy stearate, PEG-7 hydrogenated castor oil, diethyl phthalate, diethyl sebacate, dimethicone, dimethyl phthalate, PEG fatty acid esters, PEG-stearate, PEG-oleate, PEG laurate, PEG fatty acid diesters, PEG-dioleate, PEG-distearate, PEG-castor oil, glyceryl behenate, PEG glycerol fatty acid esters, PEG glyceryl laurate, PEG glyceryl stearate, PEG glyceryl oleate, lanolin, lauric diethanolamide, lauryl lactate, lauryl sulfate, medronic acid, multisterol extract, myristyl alcohol, neutral oil, PEG-octyl phenyl ether, PEG-alkyl ethers, PEG-cetyl ether, PEG-stearyl ether, PEG-sorbitan fatty acid esters, PEG-sorbitan diisosterate, PEG-sorbitan monostearate, propylene glycol fatty acid esters, propylene glycol stearate, caprylate/caprate, sodium pyrrolidone carboxylate, sorbitol, squalene, triglycerides, alkyl aryl polyether alcohols, polyoxyethylene derivatives of sorbitan-ethers, saturated polyglycolyzed C8-C10 glycerides, N-methyl pyrrolidone, honey, polyoxyethylated glycerides, dimethyl sulfoxide, azone and related compounds, dimethylformamide, N-methyl formamaide, fatty acid esters, fatty alcohol ethers, alkyl-amides, N-methyl pyrrolidone related compounds, ethyl oleate, polyglycerized fatty acids, glycerol monooleate, glyceryl monomyristate, glycerol esters of fatty acids, silk amino acids, PPG-3 benzyl ether myristate, Di-PPG2 myreth 10-adipate, honeyquat, sodium pyroglutamic acid, abyssinica oil, dimethicone, macadamia nut oil, limnanthes alba seed oil, cetearyl alcohol, PEG-50 shea butter, shea butter, aloe vera juice, phenyl trimethicone, hydrolyzed wheat protein, and combinations thereof. 
     
     
         15 . A formulation as in  claim 1 , wherein the solidifying agent includes at least one member selected from the group consisting of polyvinyl alcohol, esters of polyvinylmethylether/maleic anhydride copolymer, neutral copolymers of butyl methacrylate and methyl methacrylate, dimethylaminoethyl methacrylate-butyl methacrylate-methyl methacrylate copolymers, ethyl acrylate-methyl methacrylate-trimethylammonioethyl methacrylate chloride copolymers, prolamine, pregelatinized starch, ethyl cellulose, fish gelatin, bovine gelatin, zein, wheat protein, gluten, casein, gelatin, acrylates/octylacrylamide copolymers, and combinations thereof. 
     
     
         16 . A formulation as in  claim 1 , wherein the solidifying agent includes at least one member selected from the group consisting of ethyl cellulose, hydroxy ethyl cellulose, hydroxy methyl cellulose, hydroxy propyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, methyl cellulose, polyether amides, corn starch, pregelatinized corn starch, polyether amides, shellac, polyvinyl pyrrolidone, polyisobutylene rubber, polyvinyl acetate phthalate and combinations thereof. 
     
     
         17 . A formulation as in  claim 1 , wherein the solidifying agent includes at least one member selected from the group consisting of ammonia methacrylate, carrageenan, cellulose acetate phthalate aqueous, carboxy polymethylene, cellulose acetate, cellulose polymers, divinyl benzene styrene, ethylene vinyl acetate, silicone, guar gum, guar rosin, gluten, casein, calcium caseinate, ammonium caseinate, sodium caseinate, potassium caseinate, methyl acrylate, microcrystalline wax, polyvinyl acetate, PVP ethyl cellulose, acrylate, PEG/PVP, xantham gum, trimethyl siloxysilicate, maleic acid/anhydride copolymers, polacrilin, poloxamer, polyethylene oxide, poly glactic acid/poly-1-lactic acid, turpene resin, locust bean gum, acrylic copolymers, polyurethane dispersions, dextrin, polyvinyl alcohol-polyethylene glycol co-polymers, methacrylic acid-ethyl acrylate copolymers, methacrylic acid and methacrylate based polymers and combinations thereof. 
     
     
         18 . (canceled) 
     
     
         19 . A formulation as in  claim 1 , wherein the solidified layer is sufficiently flexible and adhesive to the skin such that when applied to the skin at a human joint, the solidified layer will remain substantially intact on the skin upon bending of the human joint. 
     
     
         20 . A formulation as in  claim 1 , wherein the formulation is formulated to deliver the corticosteroid at a therapeutically effective rate for at least 2 hours following the formation of the solidified layer. 
     
     
         21 . A formulation as in  claim 1 , wherein the formulation is formulated such that the solidified layer is formed within 15 minutes of application to standard skin at ambient conditions. 
     
     
         22 . A formulation as in  claim 1 , wherein the formulation is formulated such that the solidified layer is formed within 5 minutes of application to standard skin at ambient conditions. 
     
     
         23 . A formulation as in  claim 1 , wherein the formulation has an initial viscosity prior to skin application from about 100 to about 3,000,000 centipoises. 
     
     
         24 . A formulation as in  claim 1 , wherein the formulation has an initial viscosity prior to skin application from about 1,000 to about 1,000,000 centipoises. 
     
     
         25 . A formulation as in  claim 1 , wherein the non-volatile solvent includes at least two non-volatile solvents, and wherein at least one of the non-volatile solvents is included to improve compatibility of the non-volatile solvent system with the solidifying agent. 
     
     
         26 . A formulation as in  claim 1 , wherein the solidified layer is coherent, flexible, and continuous. 
     
     
         27 . A formulation as in  claim 1 , wherein the solidified layer, upon formation, is a soft, coherent solid that is peelable from a skin surface as a single piece or as only a few large pieces relative to the application size. 
     
     
         28 . A formulation as in  claim 1 , wherein the skin disorder is selected from the group consisting of dermatitis and psoriasis.