Claims for Patent: 11,612,573

Summary for Patent: 11,612,573

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 Doherty, Mary BEDARD, Piyush Jain
Assignee:	Dermavant Sciences GmbH , GlaxoSmithKline Intellectual Property Development Ltd
Application Number:	US16/587,833
Patent Claims:	1. A method of improving residency time of an active ingredient 3,5-Dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof in the skin of a patient in need thereof, the method comprising topically administering to the skin of said patient up to twice daily a homogenous oil-in-water emulsion composition comprising: the active ingredient 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, a first oil phase, wherein the active ingredient 3,5-Dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof is solubilized in the first oil phase, and wherein the first oil phase does not contain mineral oil or petrolatum, optionally, a second oil phase selected from the group consisting of mineral oil, petrolatum, and a combination thereof, wherein the first oil phase and, if present, the second oil phase, combined are present in an amount of about 5% to about 25% by weight based on the total weight of the composition, a water phase in an amount of about 30% to about 80% by weight, a non-ionic surfactant in an amount of about 5% to about 15% by weight, based on the total weight of the composition, wherein the non-ionic surfactant is an emulsifying wax, and an antioxidant in an amount of about 0.01% to about 1% by weight, based on the total weight of the composition, and wherein the oil-in-water emulsion composition has a D90 of about 0.1 μm to about 1 μm, and has an improved residency time, wherein the improved residency time is measured as a ratio of the active ingredient 3,5-Dihydroxy-4-isopropyl-trans-stilbene in the dermis to the cumulative amount of the active ingredient 3,5-Dihydroxy-4-isopropyl-trans-stilbene in the receiving fluid and wherein the ratio is about 909.3:1 at about 12 hours or about 1044.0:1 at about 15 hours. 2. The method of claim 1, wherein the improved residency time is measured as an in vitro skin flux. 3. The method of claim 2, wherein the in vitro skin flux is about 1,000 to about 5,000 ng/cm2/hour. 4. The method of claim 1, wherein the improved residency time appears as early as 3 hours post application and continues over 15 hours. 5. The method of claim 1, wherein the homogenous oil-in-water emulsion composition further comprises one or more additional surfactants. 6. The method of claim 1, wherein the homogenous oil-in-water emulsion composition does not comprise the second oil phase. 7. The method of claim 1, wherein the second oil phase is present and wherein the second oil phase comprises ≤3% petrolatum. 8. A method of improving residency time of an active ingredient 3,5-Dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof in the skin of a patient in need thereof, the method comprising topically administering to the skin of said patient up to twice daily a homogenous oil-in-water emulsion composition comprising: the active ingredient 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, a first oil phase, wherein the active ingredient 3,5-Dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof is solubilized in the first oil phase, and wherein the first oil phase does not contain mineral oil or petrolatum, optionally, a second oil phase selected from the group consisting of mineral oil, petrolatum, and a combination thereof, wherein the first oil phase and, if present, the second oil phase, combined are present in an amount of about 5% to about 25% by weight based on the total weight of the composition, a water phase in an amount of about 30% to about 80% by weight, a non-ionic surfactant in an amount of about 5% to about 15% by weight, based on the total weight of the composition, wherein the non-ionic surfactant is an emulsifying wax, and an antioxidant in an amount of about 0.01% to about 1% by weight, based on the total weight of the composition, and wherein the oil-in-water emulsion composition has a D90 of about 0.1 μm to about 1 μm, and has an improved residency time, and wherein the improved residency time is demonstrated by an area under the curve (AUC) of the active ingredient 3,5-Dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof below about 50 ng*h/mL. 9. The method of claim 8, wherein the improved residency time is demonstrated by an AUC of the active ingredient 3,5-Dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof below about 42.5 ng*h/mL. 10. The method of claim 8, wherein the improved residency time is demonstrated by an AUC of the active ingredient 3,5-Dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof below about 30 ng*h/mL. 11. The method of claim 8, wherein the improved residency time is demonstrated by an AUC of the active ingredient 3,5-Dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof below about 23.5 ng*h/mL. 12. The method of claim 8, wherein the improved residency time is demonstrated by an AUC (0-8 h) of the active ingredient 3,5-Dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof below about 16 ng*h/mL. 13. The method of claim 8, wherein the improved residency time is demonstrated by an AUC (0-8 h) of the active ingredient 3,5-Dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof below about 14 ng*h/mL. 14. The method of claim 8, wherein the improved residency time is demonstrated by an AUC (0-8 h) of the active ingredient 3,5-Dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof below about 11 ng*h/mL. 15. The method of claim 8, wherein the homogenous oil-in-water emulsion composition does not comprise the second oil phase. 16. The method of claim 8, wherein the second oil phase is present and wherein the second oil phase comprises ≤3% petrolatum. 17. The method of claim 8, wherein the homogenous oil-in-water emulsion composition further comprises one or more additional surfactants. 18. A method of improving residency time of an active ingredient 3,5-Dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof in the skin of a patient in need thereof, the method comprising topically administering to the skin of said patient up to twice daily a homogenous oil-in-water emulsion composition comprising: the active ingredient 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, a first oil phase, wherein the active ingredient 3,5-Dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof is solubilized in the first oil phase, and wherein the first oil phase does not contain mineral oil or petrolatum, optionally, a second oil phase selected from the group consisting of mineral oil, petrolatum, and a combination thereof, wherein the first oil phase and, if present, the second oil phase, combined are present in an amount of about 5% to about 25% by weight based on the total weight of the composition, a water phase in an amount of about 30% to about 80% by weight, a non-ionic surfactant in an amount of about 5% to about 15% by weight, based on the total weight of the composition, wherein the non-ionic surfactant is an emulsifying wax, and an antioxidant in an amount of about 0.01% to about 1% by weight, based on the total weight of the composition, and wherein the oil-in-water emulsion composition has a D90 of about 0.1 μm to about 1 μm, and has an improved residency time, and wherein the improved residency time is demonstrated by a Cmax of the active ingredient 3,5-Dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof below about 15 ng/mL. 19. The method of claim 18, wherein the improved residency time is demonstrated by a Cmax of the active ingredient 3,5-Dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof below about 12.5 ng/mL. 20. The method of claim 18, wherein the improved residency time is demonstrated by a Cmax of the active ingredient 3,5-Dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof below about 11.3 ng/mL. 21. The method of claim 18, wherein the improved residency time is demonstrated by a Cmax of the active ingredient 3,5-Dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof below about 5 ng/mL. 22. The method of claim 18, wherein the improved residency time is demonstrated by a Cmax of the active ingredient 3,5-Dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof below about 4 ng/mL. 23. The method of claim 18, wherein the improved residency time is demonstrated by a Cmax of the active ingredient 3,5-Dihydroxy-4-isopropyl-trans-stilbene or a pharmaceutically acceptable salt thereof below about 3 ng/mL. 24. The method of claim 18, wherein the homogenous oil-in-water emulsion composition does not comprise the second oil phase. 25. The method of claim 18, wherein the second oil phase is present and wherein the second oil phase comprises ≤3% petrolatum. 26. The method of claim 18, wherein the homogenous oil-in-water emulsion composition further comprises one or more additional surfactants.