Claims for Patent: 8,288,434

Summary for Patent: 8,288,434

Title:	Topical pharmaceutical formulations containing a low concentration of benzoyl peroxide in suspension in water and a water-miscible organic solvent
Abstract:	An aqueous formulation for topical application to the skin comprising water, a water-miscible organic solvent, and benzoyl peroxide, wherein the concentration of the organic solvent is sufficient to provide a stable suspension of benzoyl peroxide in the aqueous formulation without the inclusion of a surfactant in the formulation, wherein the ratio of concentrations of water and organic solvent in the formulation is sufficient to maintain the benzoyl peroxide in saturated solubility in the formulation following application to the skin, and wherein the concentration of benzoyl peroxide in the formulation is less than 5.0% and at least 1.0% w/w. The formulation may further contain a chemical compound in addition to benzoyl peroxide that is effective in the treatment of acne. The aqueous formulations of the invention are useful in the treatment of acne and acne rosacea.
Inventor(s):	Chang; Yunik (Sonoma, CA), Dow; Gordon J. (Santa Rosa, CA)
Assignee:	Dow Pharmaceutical Sciences, Inc. (Petaluma, CA)
Application Number:	12/455,525
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,288,434
Patent Claims:	1. An aqueous formulation for topical application to the skin comprising water, a water-miscible organic solvent, and benzoyl peroxide, wherein the concentration of the organic solvent is sufficient to provide a stable suspension of benzoyl peroxide in the aqueous formulation without the inclusion of a surfactant in the formulation, wherein the combined concentration of water and the organic solvent is sufficient to provide a suspension of a benzoyl peroxide in a saturated solution of benzoyl peroxide, and wherein the concentration of benzoyl peroxide in the formulation is less than 5.0% and at least 1.0% w/w. 2. The aqueous formulation of claim 1 wherein the concentration of benzoyl peroxide is between 2.0% and 3.5% w/w. 3. The aqueous formulation of claim 2 wherein the concentration of benzoyl peroxide is about 2.5% w/w. 4. The aqueous formulation of claim 1 wherein the organic solvent is a polyol. 5. The aqueous formulation of claim 4 wherein the polyol is propylene glycol. 6. The aqueous formulation of claim 1 wherein the concentration of the organic solvent is lower than that which will dissolve all of the benzoyl peroxide in the formulation following the removal of all of the water from the formulation. 7. The aqueous formulation of claim 1 wherein the concentration of the organic solvent is 1 to 4 times the concentration of the benzoyl peroxide in the formulation. 8. The aqueous formulation of claim 1 wherein the ratio of water to organic solvent in the formulation is at least 7:1. 9. The aqueous formulation of claim 8 wherein the ratio is at least 10:1. 10. The aqueous formulation of claim 9 wherein the ratio is at least 20:1. 11. The aqueous formulation of claim 1 which is free of surfactant. 12. The aqueous formulation of claim 1 which contains a surfactant. 13. The aqueous formulation of claim 1 which further comprises a water-dispersible gelling agent. 14. The aqueous formulation of claim 1 which further comprises, in addition to benzoyl peroxide, a chemical compound that is effective in the treatment of acne. 15. The aqueous formulation of claim 14 wherein the chemical compound is soluble in water. 16. The aqueous formulation of claim 14 wherein the chemical compound is an antibiotic. 17. The aqueous formulation of claim 16 wherein the antibiotic is a member of the macrolide or lincomycin families of antibiotics. 18. The aqueous formulation of claim 17 wherein the antibiotic is clindamycin. 19. A method for treating acne comprising applying to affected areas of skin an aqueous formulation for topical application to the skin comprising water, a water-miscible organic solvent, and benzoyl peroxide, wherein the concentration of the organic solvent is sufficient to provide a stable suspension of benzoyl peroxide in the aqueous formulation without the inclusion of a surfactant in the formulation, wherein the ratio of concentrations of water and organic solvent in the formulation is sufficient to maintain the suspension of benzoyl peroxide in a saturated solution of benzoyl peroxide in the formulation following application to the skin, and wherein the concentration of benzoyl peroxide in the formulation is less than 5.0% and at least 1.0% w/w for a time sufficient to ameliorate the signs and/or symptoms of acne. 20. The method of claim 19 wherein the concentration of benzoyl peroxide in the aqueous formulation is between 2.0% and 3.5% w/w. 21. The method of claim 20 wherein the concentration of benzoyl peroxide is about 2.5% w/w. 22. The method of claim 19 wherein the organic solvent is a polyol. 23. The method of claim 22 wherein the polyol is propylene glycol. 24. The method of claim 19 wherein the concentration of the organic solvent is lower than that which will dissolve all of the benzoyl peroxide in the formulation following the removal of all of the water from the formulation. 25. The method of claim 19 wherein the concentration of the organic solvent is 1 to 4 times the concentration of the benzoyl peroxide in the formulation. 26. The method of claim 19 wherein the ratio of water to organic solvent in the formulation is at least 7:1. 27. The method of claim 26 wherein the ratio is at least 10:1. 28. The method of claim 27 wherein the ratio is at least 20:1. 29. The method of claim 19 wherein the aqueous formulation is free of surfactant. 30. The method of claim 19 wherein the aqueous formulation contains a surfactant. 31. The method of claim 19 wherein the formulation further comprises a water-dispersible gelling agent. 32. The method of claim 19 wherein the formulation further comprises, in addition to benzoyl peroxide, a chemical compound that is effective in the treatment of acne. 33. The method of claim 32 wherein the chemical compound is soluble in water. 34. The method of claim 32 wherein the chemical compound is an antibiotic. 35. The method of claim 34 wherein the antibiotic is a member of the macrolide or lincomycin families of antibiotics. 36. The method of claim 35 wherein the antibiotic is clindamycin. 37. The aqueous formulation of claim 1 wherein the concentration of the organic solvent is 1 to 4 times the concentration of the benzoyl peroxide in the formulation, wherein the ratio by weight of water to organic solvent in the formulation is at least 7:1, and wherein the concentration of benzoyl peroxide in the formulation is between 1.0% and 3.5% w/w. 38. The aqueous formulation of claim 37 wherein the concentration of benzoyl peroxide in the formulation is about 2.5%. 39. The aqueous formulation of claim 16 wherein the antibiotic is azithromycin. 40. The aqueous formulation of claim 14 wherein the chemical compound is a retinoid. 41. An aqueous formulation for topical application to the skin comprising water, a water-miscible organic solvent, and benzoyl peroxide, wherein the concentration of the organic solvent is sufficient to provide a stable suspension of benzoyl peroxide in the aqueous formulation without the inclusion of a surfactant in the formulation, wherein the combined concentration of water and the organic solvent is sufficient to provide a uniform suspension and a saturated solution of benzoyl peroxide with a dissolved concentration of benzoyl peroxide that is higher than when dissolved in water without the organic solvent, and wherein the concentration of benzoyl peroxide in the formulation is less than 5.0% and at least 1.0% w/w. 42. The aqueous formulation of claim 41 wherein the concentration of benzoyl peroxide is between 2.0% and 3.5% w/w. 43. The aqueous formulation of claim 42 wherein the concentration of benzoyl peroxide is about 2.5% w/w. 44. The aqueous formulation of claim 41 wherein the organic solvent is a polyol. 45. The aqueous formulation of claim 44 wherein the polyol is propylene glycol. 46. The aqueous formulation of claim 41 wherein the concentration of the organic solvent is lower than that which will dissolve all of the benzoyl peroxide in the formulation following the removal of all of the water from the formulation. 47. The aqueous formulation of claim 41 wherein the concentration of the organic solvent is 1 to 4 times the concentration of the benzoyl peroxide in the formulation. 48. The aqueous formulation of claim 41 wherein the ratio of water to organic solvent in the formulation is at least 7:1. 49. The aqueous formulation of claim 48 wherein the ratio is at least 10:1. 50. The aqueous formulation of claim 49 wherein the ratio is at least 20:1. 51. The aqueous formulation of claim 41 which is free of surfactant. 52. The aqueous formulation of claim 41 which contains a surfactant. 53. The aqueous formulation of claim 41 which further comprises a water-dispersible gelling agent. 54. The aqueous formulation of claim 41 which further comprises, in addition to benzoyl peroxide, a chemical compound that is effective in the treatment of acne. 55. The aqueous formulation of claim 54 wherein the chemical compound is soluble in water. 56. The aqueous formulation of claim 54 wherein the chemical compound is an antibiotic. 57. The aqueous formulation of claim 55 wherein the antibiotic is a member of the macrolide or lincomycin families of antibiotics. 58. The aqueous formulation of claim 57 wherein the antibiotic is clindamycin. 59. The aqueous formulation of claim 56 wherein the antibiotic is azithromycin. 60. The aqueous formulation of claim 54 wherein the chemical compound is a retinoid.