Claims for Patent: 11,458,108

Summary for Patent: 11,458,108

Title:	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.
Inventor(s):	Sujatha D. SONTI, Joey Roger THOMAS, Jon Lenn, Leandro SANTOS, Justin WHITEMAN, Michael Quinn DOHERTY, Mary BEDARD, Piyush Jain
Assignee:	Dermavant Sciences GmbH , GlaxoSmithKline Intellectual Property Development Ltd
Application Number:	US16/229,080
Patent Claims:	1. A topical pharmaceutical oil-in-water emulsion composition consisting of: a therapeutically effective amount of 3,5-Dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof, an oil phase in an amount of about 5% to about 45% by weight, based on the total weight of the composition, a water phase in an amount of about 25% to about 85% by weight, based on the total weight of the composition, one or more surfactants in an amount of about 1% to about 20% by weight, based on the total weight of the composition, wherein the one or more surfactants comprises at least a non-ionic emulsifying wax NF, an antioxidant, and optionally one or more components selected from the group consisting of a preservative, a pH adjusting agent, a chelating agent, and a co-solvent, wherein an average droplet size of the oil phase is about 0.1 micron to about 0.75 microns, wherein the oil phase contains <3% petrolatum, wherein the 3,5-Dihydroxy-4-isopropyl-trans-stilbene or the pharmaceutically acceptable salt thereof is solubilized in the oil phase, and wherein the topical pharmaceutical oil-in-water emulsion composition is stable, homogeneous and a cream and has a pH of about 4 to about 7. 2. The topical pharmaceutical oil-in-water emulsion composition of claim 1, wherein the effective amount of 3,5-Dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof, is about 0.5% by weight, based on the total weight of the composition. 3. The topical pharmaceutical oil-in-water emulsion composition of claim 1, wherein the effective amount of 3,5-Dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof, is about 1% by weight, based on the total weight of the composition. 4. The topical pharmaceutical oil-in-water emulsion composition of claim 1, wherein the oil phase in an amount of about 5% to about 25% by weight, based on the total weight of the composition. 5. The topical pharmaceutical oil-in-water emulsion composition of claim 1, wherein the surfactant 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 surfactant is at an amount of about 5% to about 15% by weight, based on the total weight of the composition and the oil phase is at an amount of about 5% to about 15% 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 comprises medium chain triglycerides of a carbon length from six to twelve carbons. 8. 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. 9. The topical pharmaceutical oil-in-water emulsion composition of claim 1, wherein the oil phase is substantially free of mineral oil. 10. The topical pharmaceutical oil-in-water emulsion composition of claim 1, wherein the oil phase is substantially free of petrolatum. 11. The topical pharmaceutical oil-in-water emulsion composition of claim 1, wherein the antioxidant is in an amount of 0.01% to 1% by weight, based on the total weight of the composition. 12. The topical pharmaceutical oil-in-water emulsion composition of claim 1, wherein the pH adjusting agent is present and the pH adjusting agent is in an amount of 0.01% to 10% by weight, based on the total weight of the composition. 13. The topical pharmaceutical oil-in-water emulsion composition of claim 12, 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. 14. The topical pharmaceutical oil-in-water emulsion composition of claim 12, wherein the pH adjusting agent is a buffer and 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. 15. The topical pharmaceutical oil-in-water emulsion composition of claim 1, wherein the chelating agent is present and the chelating agent is in an amount of 0.01% to 1% by weight, or 0.1% by weight, based on the total weight of the composition. 16. The topical pharmaceutical oil-in-water emulsion composition of claim 15, 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. 17. The topical pharmaceutical oil-in-water emulsion composition of claim 1, wherein the preservative is present and the preservative is in an amount of 0.01% to 2% by weight, or 0.25% by weight, based on the total weight of the composition. 18. The topical pharmaceutical oil-in-water emulsion composition of claim 17, 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. 19. The topical pharmaceutical oil-in-water emulsion composition of claim 1, wherein the co-solvent is present and the co-solvent is in an amount of 5% to 20% by weight, based on the total weight of the composition. 20. The topical pharmaceutical oil-in-water emulsion composition of claim 19, wherein the co-solvent is a mixture of propylene glycol and diethylene glycol monoethyl ether. 21. The topical pharmaceutical oil-in-water emulsion composition of claim 1, consisting of: a therapeutically effective amount of 3,5-Dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof, an oil phase in an amount of about 5% to about 15% by weight, based on the total weight of the composition, a water phase in an amount of about 55% to about 75% by weight, based on the total weight of the composition, a surfactant in an amount of about 5% to about 15% by weight, based on the total weight of the composition, wherein the surfactant comprises at least one non-ionic emulsifying wax NF, and an antioxidant, and optionally a preservative, a pH adjusting agent, a chelating agent, a co-solvent or combinations thereof. 22. The topical pharmaceutical oil-in-water emulsion composition of claim 1, wherein the oil phase contains ≤2% petrolatum. 23. The topical pharmaceutical oil-in-water emulsion composition of claim 1, wherein the oil phase contains ≤1% petrolatum. 24. The topical pharmaceutical oil-in-water emulsion composition of claim 1, wherein the oil phase is free of petrolatum. 25. The topical pharmaceutical oil-in-water emulsion composition of claim 1, wherein the composition is stable for up to 6 months when stored at standard ICH conditions. 26. The topical pharmaceutical oil-in-water emulsion composition of claim 1, wherein at least about 75% of the droplets have a droplet size of 0.1 micron to 0.75 microns. 27. The topical pharmaceutical oil-in-water emulsion composition of claim 1, wherein at least about 80% of the droplets have a droplet size of 0.1 micron to 0.75 microns. 28. The topical pharmaceutical oil-in-water emulsion composition of claim 1, wherein at least about 85% of the droplets have a droplet size of 0.1 micron to 0.75 microns. 29. The topical pharmaceutical oil-in-water emulsion composition of claim 1, wherein at least about 90% of the droplets have a droplet size of 0.1 micron to 0.75 microns. 30. The topical pharmaceutical oil-in-water emulsion composition of claim 1, wherein at least about 95% of the droplets have a droplet size of 0.1 micron to 0.75 microns. 31. The topical pharmaceutical oil-in-water emulsion composition of claim 1, wherein at least about 75% to about 95% of the droplets have a droplet size of 0.1 micron to 0.75 microns.