Claims for Patent: 11,992,480

Summary for Patent: 11,992,480

Title:	Method for reducing side effects from administration of phosphodiesterase-4 inhibitors
Abstract:	A method for altering the PK profile of a pharmaceutical formulation containing a PDE-4 inhibitor, such as roflumilast, to reduce the spike in Cmax. The spike in Cmax is reduced by topically administering the PDE-4 inhibitor in combination with one or more phosphate ester surfactants. Reducing the spike in Cmax will reduce gastrointestinal side effects and result in better patient compliance.
Inventor(s):	David W. Osborne, Howard Welgus
Assignee:	Arcutis Biotherapeutics Inc
Application Number:	US17/327,236
Patent Claims:	1. A method for reducing gastrointestinal side effects of roflumilast relative to an oral roflumilast formulation marketed under the trademark DALIRESP®, comprising topically administering to said patient, a composition comprising (i) roflumilast in an amount of 0.05%-1% w/w and (ii) a phosphate ester surfactant blend comprising cetostearyl alcohol, dicetyl phosphate and ceteth-10 phosphate in an amount of 1.0-25% w/w. 2. The method of claim 1, wherein the patient is suffering from an inflammatory dermatoses. 3. The method of claim 2, wherein said roflumilast is in an amount of 0.05% w/w. 4. The method of claim 2, wherein said roflumilast is present in an amount of 0.15% w/w. 5. The method according to claim 2, wherein said roflumilast is in an amount of 0.3% w/w. 6. The method of claim 2, wherein said composition is a foam, wherein said roflumilast is present in an amount 0.3% w/w, wherein said phosphate surfactant blend is present in an amount of 1.0%-10% w/w, wherein said composition further comprises diethylene glycol monoethyl ether and water. 7. The method of claim 6, wherein said patient is suffering from atopic dermatitis. 8. The method of claim 6, wherein said patient is suffering from psoriasis. 9. The method of claim 6, wherein said patient is suffering from seborrheic dermatitis. 10. The method of claim 2, wherein said composition is a cream, wherein said roflumilast is present in an amount 0.3% w/w, wherein said phosphate surfactant blend is present in an amount of 2.5%-20% w/w, wherein said composition further comprises diethylene glycol monoethyl ether and water, wherein said patient is suffering from psoriasis. 11. The method of claim 10, wherein said phosphate surfactant blend is present in an amount of 5%-15% w/w. 12. The method of claim 11, wherein said phosphate surfactant blend is present in an amount of 10% w/w. 13. The method of claim 2, wherein said composition is a cream, wherein said roflumilast is present in an amount 0.15% w/w, wherein said phosphate surfactant blend is present in an amount of 2.5%-20% w/w, wherein said composition further comprises diethylene glycol monoethyl ether and water, wherein said patient is suffering from atopic dermatitis. 14. The method of claim 13, wherein said phosphate surfactant blend is present in an amount of 5%-15% w/w. 15. The method of claim 14, wherein said phosphate surfactant blend is present in an amount of 10% w/w. 16. The method of claim 2, wherein said composition is a cream, wherein said roflumilast is present in an amount 0.05% w/w, wherein said phosphate surfactant blend is present in an amount of 2.5%-20% w/w, wherein said composition further comprises diethylene glycol monoethyl ether and water, wherein said patient is suffering from atopic dermatitis. 17. The method of claim 16, wherein said phosphate surfactant blend is present in an amount of 5%-15% w/w. 18. The method of claim 17, wherein said phosphate surfactant blend is present in an amount of 10% w/w. 19. The method of claim 1, wherein said composition is a cream or a foam. 20. The method of claim 19, wherein said composition further comprises hexylene glycol in an amount of 0.1-20% w/w. 21. The method of claim 1, wherein said composition further comprises at least one additional component selected from the group consisting of a solvent, moisturizer, preservative, pH adjusting solution, and skin penetration enhancer. 22. The method of claim 1, wherein said phosphate ester surfactant blend is in an amount of 10% w/w. 23. The method of claim 1, wherein said composition further comprises diethylene glycol monoethyl ether and water. 24. The method of claim 23, wherein said composition comprises diethylene glycol monoethyl ether in an amount of 25% w/w. 25. The method of claim 1, wherein said patient is suffering from psoriasis, atopic dermatitis or seborrheic dermatitis. 26. The method of claim 25, wherein said patient is suffering from atopic dermatitis. 27. The method of claim 25, wherein said patient is suffering from psoriasis. 28. The method of claim 1, wherein said composition further comprises diethylene glycol monoethyl ether in an amount of 10-40% w/w. 29. A method for reducing gastrointestinal side effects of roflumilast relative to an oral roflumilast formulation marketed under the trademark DALIRESP®, comprising topically administering to said patient a composition comprising (i) roflumilast in an amount of 0.05%-1% w/w and (ii) a phosphate ester surfactant blend comprising cetostearyl alcohol, dicetyl phosphate and ceteth-10 phosphate in an amount of 1.0-25% w/w, wherein the peak to trough ratio of roflumilast blood plasma concentration is less than 2 after multiple daily administrations, and wherein the patient is suffering from an inflammatory dermatoses. 30. The method of claim 29, wherein the peak to trough ratio is less than 2 at steady state. 31. The method of claim 29, wherein the peak to trough ratio is approximately 1 at steady state. 32. The method of claim 29, wherein said composition is a cream, and said phosphate ester surfactant blend is in an amount of 10% w/w. 33. The method of claim 29, wherein said composition is a foam, and said phosphate ester surfactant blend is in an amount of 2% w/w. 34. The method of claim 29, wherein said composition further comprises diethylene glycol monoethyl ether and water. 35. The method of claim 34, wherein said diethylene glycol monoethyl ether is in an amount of 10-40% w/w. 36. The method of claim 35, wherein said diethylene glycol monoethyl ether is in an amount of 25% w/w. 37. The method of claim 29, wherein said patient is suffering from psoriasis, atopic dermatitis or seborrheic dermatitis. 38. A method for reducing gastrointestinal side effects of a topical roflumilast composition, comprising adding a phosphate ester surfactant blend in an amount of 1.0-25% w/w to a composition comprising roflumilast in an amount of 0.05%-1% w/w and a pharmaceutically acceptable solvent, wherein the phosphate ester surfactant blend comprises cetostearyl alcohol, dicetyl phosphate and ceteth-10 phosphate. 39. The method of claim 38, wherein said composition is a cream, and said phosphate ester surfactant blend is in an amount of 10% w/w. 40. The method of claim 38, wherein said pharmaceutically acceptable solvent comprises diethylene glycol monoethyl ether. 41. The method of claim 40, wherein said diethylene glycol monoethyl ether is in an amount of 10-40% w/w. 42. The method of claim 41, wherein said diethylene glycol monoethyl ether is in an amount of 15-30% w/w. 43. The method of claim 42, wherein said diethylene glycol monoethyl ether is in an amount of 25% w/w.