Topical pharmaceutical compositions

Abstract

The present invention relates to topical pharmaceutical emulsion compositions comprising a therapeutically effective amount of 3,5-Dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof, an oil phase, a water phase, a surfactant, and an antioxidant, and wherein the emulsion composition is homogeneous and/or the active is solubilized in the oil phase. The invention also relates to methods of treating a dermatological condition or disorder in a patient by administering the present compositions to the skin of the patient.

What is claimed is: 
     
         1 . A topical pharmaceutical oil-in-water emulsion composition comprising:
 3,5-dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof in an amount of about 0.5% to about 2% by weight, based on the total weight of the composition;   an oil phase in an amount of about 2% to about 30% by weight, based on the total weight of the composition, wherein the oil phase comprises medium chain triglycerides of a carbon length from six to twelve carbons;   a water phase in an amount of about 30% to about 80% by weight, based on the total weight of the composition;   a surfactant in an amount of about 1% to about 20% by weight, based on the total weight of the composition, wherein the surfactant comprises at least one non-ionic emulsifying wax NF;   a dermatologically acceptable excipient selected from the group consisting of an antioxidant, a pH adjusting agent, a chelating agent, a preservative, a co-solvent, a penetration enhancer, a humectant, a thickening agent, a gelling agent, a viscosity building agent, a fragrance, a colorant, and combinations thereof;   wherein the 3,5-dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof is solubilized in the oil phase;   wherein the oil phase contains less than 3% of petrolatum;   wherein the D90 average droplet size of the oil phase is from about 0.5 microns to about 1 micron; and   wherein the pH is about 2 to about 6.   
     
     
         2 . The topical pharmaceutical oil-in-water emulsion composition of  claim 1 , wherein the 3,5-dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof is the only active ingredient in the oil phase. 
     
     
         3 . The topical pharmaceutical oil-in-water emulsion composition of  claim 1 , wherein the medium chain triglyceride carbon length is from C6 to C8. 
     
     
         4 . The topical pharmaceutical oil-in-water emulsion composition of  claim 1 , wherein the medium chain triglycerides are in an amount of about 5% to about 20% by weight, based on the total weight of the composition. 
     
     
         5 . The topical pharmaceutical oil-in-water emulsion composition of  claim 1 , wherein the medium chain triglycerides are in an amount of about 5% to about 15% by weight, based on the total weight of the composition. 
     
     
         6 . The topical pharmaceutical oil-in-water emulsion composition of  claim 1 , wherein the medium chain triglycerides are in an amount of about 10% by weight, based on the total weight of the composition. 
     
     
         7 . The topical pharmaceutical oil-in-water emulsion composition of  claim 1 , wherein the oil phase further comprises another oil selected from the group consisting of a fatty acid, an ester, an ester of glycerin, a fatty alcohol, a wax, a sterol, a siloxane, a silane, a hydrocarbon, an essential oil, a vegetable oil, a mineral oil, an animal oil, an edible oil and mixtures thereof. 
     
     
         8 . The topical pharmaceutical oil-in-water emulsion composition of  claim 1 , wherein the water phase is in an amount of about 55% to about 75% by weight, based on the total weight of the composition. 
     
     
         9 . The topical pharmaceutical oil-in-water emulsion composition of  claim 1 , wherein the surfactant is in an amount of about 5% to about 15% by weight, based on the total weight of the composition. 
     
     
         10 . The topical pharmaceutical oil-in-water emulsion composition of  claim 1 , wherein the at least one non-ionic emulsifying wax NF is a mixture of cetostearyl alcohol and a polysorbate. 
     
     
         11 . The topical pharmaceutical oil-in-water emulsion composition of  claim 1 , wherein the surfactant comprises a mixture of the at least one non-ionic emulsifying wax NF and a surfactant selected from the group consisting of ethoxylated fatty alcohol ethers, a sorbitan derivative, and combinations thereof. 
     
     
         12 . The topical pharmaceutical oil-in-water emulsion composition of  claim 1 , wherein the surfactant comprises a mixture of the at least one non-ionic emulsifying wax NF and a surfactant selected from the group consisting of steareth-2, steareth-20, polysorbate 80, and combinations thereof. 
     
     
         13 . The topical pharmaceutical oil-in-water emulsion composition of  claim 1 , wherein the surfactant is a mixture of the at least one non-ionic emulsifying wax NF, steareth-2, steareth-20, and polysorbate 80. 
     
     
         14 . The topical pharmaceutical oil-in-water emulsion composition of  claim 1 , wherein the dermatologically acceptable excipient is an antioxidant. 
     
     
         15 . The topical pharmaceutical oil-in-water emulsion composition of  claim 14 , wherein the antioxidant is in an amount of about 0.001% to about 5% by weight, based on the total weight of the composition. 
     
     
         16 . The topical pharmaceutical oil-in-water emulsion composition of  claim 14 , wherein the antioxidant is in an amount of about 0.01% to 1% by weight, based on the total weight of the composition. 
     
     
         17 . The topical pharmaceutical oil-in-water emulsion composition of  claim 14 , wherein the antioxidant is in an amount of about 0.05% by weight, based on the total weight of the composition. 
     
     
         18 . The topical pharmaceutical oil-in-water emulsion composition of  claim 14 , wherein the antioxidant is in an amount of about 0.1% by weight, based on the total weight of the composition. 
     
     
         19 . The topical pharmaceutical oil-in-water emulsion composition of  claim 14 , wherein the antioxidant is selected from the group consisting of propyl gallate, butylated hydroxytoluene, and tocopherol. 
     
     
         20 . The topical pharmaceutical oil-in-water emulsion composition of  claim 14 , wherein the antioxidant is butylated hydroxytoluene. 
     
     
         21 . The topical pharmaceutical oil-in-water emulsion composition of  claim 14 , wherein the antioxidant is butylated hydroxytoluene in an amount of about 0.1% by weight, based on the total weight of the composition. 
     
     
         22 . The topical pharmaceutical oil-in-water emulsion composition of  claim 1 , wherein the dermatologically acceptable excipient is a pH adjusting agent. 
     
     
         23 . The topical pharmaceutical oil-in-water emulsion composition of  claim 22 , wherein the pH adjusting agent is selected from an acid, an acid salt, or a mixture thereof. 
     
     
         24 . The topical pharmaceutical oil-in-water emulsion composition of  claim 22 , wherein the pH adjusting agent is selected from the group consisting of lactic acid, acetic acid, maleic acid, succinic acid, citric acid, benzoic acid, boric acid, sorbic acid, tartaric acid, edetic acid, phosphoric acid, nitric acid, sulphuric acid and hydrochloric acid, and mixtures thereof. 
     
     
         25 . The topical pharmaceutical oil-in-water emulsion composition of  claim 22 , wherein the pH adjusting agent is a buffer. 
     
     
         26 . The topical pharmaceutical oil-in-water emulsion composition of  claim 25 , wherein the buffer is selected from the group consisting of citrate/citric acid, acetate/acetic acid, phosphate/phosphoric acid, propionate/propionic acid, lactate/lactic acid, ammonium/ammonia, and edetate/edetic acid. 
     
     
         27 . The topical pharmaceutical oil-in-water emulsion composition of  claim 22 , wherein the pH adjusting agent is a citrate/citric acid buffer. 
     
     
         28 . The topical pharmaceutical oil-in-water emulsion composition of  claim 22 , wherein the pH adjusting agent is a citrate/citric acid buffer in an amount of about 0.27% by weight, based on the total weight of the composition. 
     
     
         29 . The topical pharmaceutical oil-in-water emulsion composition of  claim 22 , wherein the pH adjusting agent is in an amount of from about 0.01% to about 10% by weight, based on the total weight of the composition. 
     
     
         30 . The topical pharmaceutical oil-in-water emulsion composition of  claim 1 , wherein the dermatologically acceptable excipient is a chelating agent. 
     
     
         31 . The topical pharmaceutical oil-in-water emulsion composition of  claim 30 , wherein the chelating agent is selected from the group consisting of citric acid, glucuronic acid, sodium hexametaphosphate, zinc hexametaphosphate, ethylene diamine tetraacetic acid, phosphonates, salts thereof, and mixtures thereof. 
     
     
         32 . The topical pharmaceutical oil-in-water emulsion composition of  claim 30 , wherein the chelating agent is ethylene diamine tetraacetic acid or a salt thereof. 
     
     
         33 . The topical pharmaceutical oil-in-water emulsion composition of  claim 30 , wherein the chelating agent is in an amount of about 0.01% to about 1% by weight, based on the total weight of the composition. 
     
     
         34 . The topical pharmaceutical oil-in-water emulsion composition of  claim 30 , wherein the chelating agent is in an amount of about 0.1% by weight, based on the total weight of the composition. 
     
     
         35 . The topical pharmaceutical oil-in-water emulsion composition of  claim 1 , wherein the dermatologically acceptable excipient is a preservative. 
     
     
         36 . The topical pharmaceutical oil-in-water emulsion composition of  claim 35 , wherein the preservative is selected from the group consisting of benzyl alcohol, imidazolidinyl urea, diazolidinyl urea, dichlorobenzyl alcohol, chloroxylenol, methyl paraben, ethyl paraben, propyl paraben, butyl paraben, phenoxyethanol, sorbic acid, benzoic acid, salts thereof, and mixtures thereof. 
     
     
         37 . The topical pharmaceutical oil-in-water emulsion composition of  claim 35 , wherein the preservative is benzoic acid. 
     
     
         38 . The topical pharmaceutical oil-in-water emulsion composition of  claim 35 , wherein the preservative is benzoic acid in an amount of about 0.25% by weight, based on the total weight of the composition. 
     
     
         39 . The topical pharmaceutical oil-in-water emulsion composition of  claim 35 , wherein the preservative is in an amount of about 0.01% to about 2% by weight, based on the total weight of the composition. 
     
     
         40 . The topical pharmaceutical oil-in-water emulsion composition of  claim 35 , wherein the preservative is in an amount of about 0.25% by weight, based on the total weight of the composition. 
     
     
         41 . The topical pharmaceutical oil-in-water emulsion composition of  claim 1 , wherein the dermatologically acceptable excipient is a co-solvent. 
     
     
         42 . The topical pharmaceutical oil-in-water emulsion composition of  claim 41 , wherein the co-solvent is in an amount of about 5% to about 20% by weight, based on the total weight of the composition. 
     
     
         43 . The topical pharmaceutical oil-in-water emulsion composition of  claim 41 , wherein the co-solvent is a mixture of propylene glycol and diethylene glycol monoethyl ether. 
     
     
         44 . The topical pharmaceutical oil-in-water emulsion composition of  claim 43 , wherein the propylene glycol is in an amount of about 10% by weight, based on the total weight of the composition. 
     
     
         45 . The topical pharmaceutical oil-in-water emulsion composition of  claim 43 , wherein the diethylene glycol monoethyl ether is in an amount of about 2% by weight, based on the total weight of the composition. 
     
     
         46 . The topical pharmaceutical oil-in-water emulsion composition of  claim 1 , wherein the pH is from about 4 to about 6. 
     
     
         47 . The topical pharmaceutical oil-in-water emulsion composition of  claim 1 , wherein the pH is from about 4.5 to about 6. 
     
     
         48 . The topical pharmaceutical oil-in-water emulsion composition of  claim 1 , wherein the D90 of the average droplet size of the oil phase is about 0.5 microns to about 0.75 microns. 
     
     
         49 . The topical pharmaceutical oil-in-water emulsion composition of  claim 1 , wherein the D90 of the average droplet size of the oil phase is about 0.5 microns. 
     
     
         50 . The topical pharmaceutical oil-in-water emulsion composition of  claim 1 , wherein the composition is selected from a lotion, foam, cream, or gel.