Claims for Patent: 11,129,818

Summary for Patent: 11,129,818

Title:	Topical roflumilast formulation having improved delivery and plasma half life
Abstract:	The present invention is directed to methods for improving the therapeutic outcome of treatment with roflumilast. The therapeutic outcome is improved by consistent delivery and/or a longer plasma half-life of a topically administered roflumilast composition. The roflumilast composition preferably includes dicetyl phosphate, ceteth-10 phosphate, diethylene glycol monoethyl ether, and/or hexylene glycol.
Inventor(s):	Osborne; David W. (Fort Collins, CO), Chaudhuri; Bhaskar (Westlake Village, CA), Thurston, Jr.; Archie W. (San Diego, CA)
Assignee:	Arcutis Biotherapeutics, Inc. (Westlake Village, CA)
Application Number:	16/778,845
Patent Claims:	1. A method for improving treatment adherence by improving delivery and extending the plasma half-life of a roflumilast composition, comprising (a) adding hexylene glycol, diethylene glycol monoethyl ether, dicetyl phosphate and ceteth-10 phosphate to a composition comprising roflumilast, (b) topically administering said composition to a patient in need of treatment with roflumilast, on a dosing regimen, and (c) continuing said dosing regimen after multiple administrations when said patient misses at least one dose, wherein the plasma half-life of said roflumilast remains at a therapeutically effective dose level. 2. The method according to claim 1, wherein said patient misses two consecutive doses. 3. The method according to claim 1, wherein said patient misses two or more non-consecutive doses. 4. The method according to claim 1, wherein said dicetyl phosphate and ceteth-10 phosphate are added as part of a surfactant blend. 5. The method according to claim 4, wherein said surfactant blend comprises dicetyl phosphate, ceteth-10 phosphate and cetearyl alcohol. 6. The method according to claim 5, wherein said surfactant blend is in an amount of 10% w/w. 7. The method according to claim 1, wherein said roflumilast composition is selected from the group consisting of an oil in water emulsion, a thickened aqueous gel, a thickened hydroalcoholic gel, a hydrophilic gel, and a hydrophilic or hydrophobic ointment. 8. The method according to claim 1, wherein said roflumilast composition further comprises an additional active agent selected from the group consisting of Anthralin, Azathioprine, Tacrolimus, Coal tar, Methotrexate, Methoxsalen, Salicylic acid, Ammonium lactate, Urea, Hydroxyurea, 5-fluorouracil, Propylthouracil, 6-thioguanine, Sulfasalazine, Mycophenolate mofetil, Fumaric acid esters, Corticosteroids, Corticotropin, Vitamin D analogues, Acitretin, Tazarotene, Cyclosporine, Resorcinol, Colchicine, Adalimumab, Ustekinumab, Infliximab, bronchodialators, and antibiotics. 9. The method according to claim 1, wherein said composition comprises carriers suitable for topical administration. 10. A method for improving the therapeutic outcome of treatment with roflumilast, comprising topically administering a composition comprising hexylene glycol, diethylene glycol monoethyl ether, dicetyl phosphate, ceteth-10 phosphate and roflumilast to a patient in need of such treatment one or more times daily, wherein said patient misses at least one dose but no more than two consecutive doses, and the plasma concentration of roflumilast decreases by less than 50%. 11. The method according to claim 10, wherein said patient is suffering from atopic dermatitis. 12. The method according to claim 10, wherein after three days of missed dosing, the plasma concentration of roflumilast decreases by less than 50%. 13. The method according to claim 10, wherein the composition comprises: TABLE-US-00008 roflumilast 0.3% w/w white petrolatum 10.0% w/w isopropyl palmitate 5.0% w/w cetearyl alcohol, dicetyl 10.0% w/w phosphate and ceteth-10 phosphate hexylene glycol 2.0% w/w diethylene glycol monoethyl 25.0% w/w ether methylparaben 0.2% w/w propylparaben 0.05% w/w, and purified water q.s. ad 100 (47.25%), wherein the pH is adjusted to 5.5. 14. The method according to claim 10, wherein said patient misses two consecutive doses and the plasma concentration of roflumilast decreases by less than 50%.