Topical pharmaceutical formulations containing a low concentration of benzoyl peroxide in suspension in water and a water-miscible organic solvent

• US 20090306172A1
• Filed: 06/03/2009
• Published: 12/10/2009
• Est. Priority Date: 06/05/2008
• Status: Active Grant

• Current Assignee: Bausch Health Ireland Limited (Bausch Health Cos., Inc.)
• Original Assignee: Dow Pharmaceutical Sciences Incorporated (Bausch Health Cos., Inc.)
• Inventors: Chang, Yunik, Dow, Gordon J.
• Granted Patent: US 8,288,434 B2
• Time in Patent Office: Days
• US Class Current: 514/422
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 2800/33 Free of surfactant
• CPC Class Codes: A61K 2800/413 Nanosized, i.e. having sizes below 100 nm
• CPC Class Codes: A61K 31/075 Ethers or acetals
• CPC Class Codes: A61K 31/235 having an aromatic ring attached to a carboxyl group
• CPC Class Codes: A61K 31/327 Peroxy compounds, e.g. hydroperoxides, peroxides, peroxyacids
• CPC Class Codes: A61K 31/7056 containing five-membered rings with nitrogen as a ring hetero atom
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 8/0241 Containing particulates characterized by their shape and/or structure see also A61K8/04, A61K8/11, and A61K8/14, further aspects are classified in A61K2800/40 and subcodes
• CPC Class Codes: A61K 8/042 Gels
• CPC Class Codes: A61K 8/044 Suspensions
• CPC Class Codes: A61K 8/345 containing more than one hydroxy group
• CPC Class Codes: A61K 8/38 Percompounds, e.g. peracids
• CPC Class Codes: A61K 8/55 Phosphorus compounds
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61Q 19/00 : Preparations for care of the skin

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.

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 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.

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 w/w 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 making an aqueous formulation for topical application to the skin comprising combining water, a water-miscible organic solvent, and benzoyl peroxide, wherein the concentration of the organic solvent that is combined 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 that are combined 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 that is combined in the formulation is less than 5.0% and at least 1.0% w/w.

20. The method of claim 19 wherein the concentration of benzoyl peroxide 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 that is combined 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 that is combined is 1 to 4 times the concentration of the benzoyl peroxide that is combined in the formulation.

26. The method of claim 19 wherein the ratio w/w of water to organic solvent that is combined 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 a surfactant is not combined in the formulation.

30. The method of claim 19 wherein a surfactant is combined in the formulation.

31. The method of claim 19 which further comprises combining a water-dispersible gelling agent in the formulation.

32. The method of claim 19 which further comprises combining a chemical compound, in addition to benzoyl peroxide, 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. 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 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 for a time sufficient to ameliorate the signs and/or symptoms of acne.

38. The method of claim 37 wherein the concentration of benzoyl peroxide in the aqueous formulation is between 2.0% and 3.5% w/w.

39. The method of claim 38 wherein the concentration of benzoyl peroxide is about 2.5% w/w.

40. The method of claim 37 wherein the organic solvent is a polyol.

41. The method of claim 40 wherein the polyol is propylene glycol.

42. The method of claim 37 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.

43. The method of claim 37 wherein the concentration of the organic solvent is 1 to 4 times the concentration of the benzoyl peroxide in the formulation.

44. The method of claim 37 wherein the ratio w/w of water to organic solvent in the formulation is at least 7:

1.

45. The method of claim 44 wherein the ratio is at least 10:

1.

46. The method of claim 45 wherein the ratio is at least 20:

1.

47. The method of claim 37 wherein the aqueous formulation is free of surfactant.

48. The method of claim 37 wherein the aqueous formulation contains a surfactant.

49. The method of claim 37 wherein the formulation further comprises a water-dispersible gelling agent.

50. The method of claim 37 wherein the formulation further comprises, in addition to benzoyl peroxide, a chemical compound that is effective in the treatment of acne.

51. The method of claim 50 wherein the chemical compound is soluble in water.

52. The method of claim 50 wherein the chemical compound is an antibiotic.

53. The method of claim 52 wherein the antibiotic is a member of the macrolide or lincomycin families of antibiotics.

54. The method of claim 53 wherein the antibiotic is clindamycin.