Methods and dosage forms for increasing solubility of drug compositions for controlled delivery

• US 20050169992A1
• Filed: 12/22/2004
• Published: 08/04/2005
• Est. Priority Date: 12/23/2003
• Status: Abandoned Application

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Skluzacek, Robert R., Edgren, David E., Yam, Noymi V., Jao, Frank
• Application Number:
  US11/023,257
• Publication Number:
  US 20050169992A1
• Time in Patent Office: Days
• US Class Current: 424/468
• CPC Class Codes: A61K 31/7004 Monosaccharides having only carbon, hydrogen and oxygen atoms
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61P 9/06 Antiarrhythmics

Abstract

Dosage forms and devices for enhancing controlled delivery of pharmaceutical agents by use of a drug core composition that increases the solubility of the pharmaceutical agent are described. The present invention provides a means of delivering high doses of poorly soluble drug in oral drug delivery systems that are convenient to swallow, for once-a-day administration.

Claims

1. A controlled release therapeutic composition comprising a low solubility therapeutic agent, a structural polymer carrier and a solubilizing surfactant selected from a polyoxyl stearate, poloxamer, sugar ester surfactant, or mixtures thereof.

2. A controlled release therapeutic composition comprising a low solubility. therapeutic agent, a structural polymer carrier and a solubilizing surfactant adapted to release a high dose of the therapeutic agent, wherein said surfactant is selected from a polyoxyl stearate, poloxamer, sugar ester surfactant, or mixtures thereof.

3. The composition of claim 2, wherein the therapeutic agent is present in an amount between about 1 μ

g and 750 mg.

4. The composition of claim 2, wherein the therapeutic agent is present in an amount between about 10 mg and about 250 mg.

5. The composition of claim 2, wherein the therapeutic agent is present in an amount between about 25 mg and about 400 mg.

6. The composition of claim 2, wherein the therapeutic agent has an aqueous solubility of less than about 1 μ

g/ml.

7. The composition of claim 2, wherein the therapeutic agent has an aqueous solubility that is between about 1 μ

g/ml and about 100 mg/ml.

8. The composition of claim 7, wherein the therapeutic agent has an aqueous solubility that is between about 1 μ

g/ml and about 50 mg/ml.

9. The composition of claim 2, wherein the amount of structural polymer is between about 1% and 80% by weight of the composition.

10. The composition of claim 9, wherein the amount of structural polymer is between about 5% and 50% by weight of the composition.

11. The composition of claim 10, wherein the amount of structural polymer is between about 5% and 15% by weight of the composition.

12. The composition of claim 2, wherein the structural polymer is polyethylene oxide of about 100,000 to 300,000 molecular weight.

13. The composition of claim 2, wherein the solubilizing surfactant is polyoxyl 40 stearate, polyoxyl 50 stearate, polyoxyl 100 stearate, polyoxyl 12 distearate, polyoxyl 32 distearate, polyoxyl 150 distearate, or mixtures thereof.

14. The composition of claim 2, wherein the sugar ester surfactant is a sugar fatty acid monoester, a sugar fatty acid diester, or mixtures thereof.

15. The composition of claim 2, wherein the sugar ester surfactant comprises at least one saccharide unit.

16. The composition of claim 14, wherein the sugar fatty acid monoester, the sugar fatty acid diester, or both, comprises sucrose.

17. The composition of claim 2, wherein the solubilizing surfactant is in micronized form having a nominal particle size of less than about 50 microns in diameter.

18. The composition of claim 2, wherein the therapeutic agent is in micronized form having a nominal particle size of less than about 50 microns in diameter.

19. The composition of claim 14, wherein the sugar fatty acid monoester, the sugar fatty acid diester, or both, comprises a fatty acid having from 6 to 24 carbon atoms.

20. The composition of claim 2, wherein the amount of solubilizing surfactant is between about 1% and 50% by weight of the composition.

21. The composition of claim 12, wherein the amount of solubilizing surfactant is between about 1% and 40% by weight of the composition.

22. The composition of claim 2, wherein the therapeutic agent is topiramate or salts or derivatives thereof.

23. A composition comprising a low solubility therapeutic agent, a structural polymer and a solubilizing surfactant adapted to release the therapeutic agent over a prolonged period of time, wherein said surfactant is selected from a polyoxyl stearate, poloxamer, sugar ester surfactant, or mixtures thereof.

24. The composition of claim 23, wherein the low solubility therapeutic agent is present in an amount between about 1 μ

g and 750 mg.

25. The composition of claim 24, wherein the low solubility therapeutic agent is present in amount between about 10 mg and about 250 mg.

26. The composition of claim 25, wherein the low solubility therapeutic agent is present in an amount between about 25 mg and about 400 mg.

27. The composition of claim 23, wherein the low solubility therapeutic agent has an aqueous solubility that is less than about 1 μ

g/ml.

28. The composition of claim 23, wherein the low solubility therapeutic agent has a solubility that is between about 1 μ

g/ml and about 100 mg/ml.

29. The composition of claim 28, wherein the low solubility therapeutic agent has a solubility that is between about 1 μ

g/ml and about 50 mg/ml.

30. The composition of claim 23, wherein the amount of structural polymer is between about 1% and 80% by weight of the composition.

31. The composition of claim 30, wherein the amount of structural polymer is between about 5% and 50% by weight of the composition.

32. The composition of claim 31, wherein the amount of structural polymer is between about 5% and 15% by weight of the composition.

33. The composition of claim 23, wherein the structural polymer is polyethylene oxide of about 100,000 to 300,000 molecular weight.

34. The composition of claim 23, wherein the solubilizing surfactant is polyoxyl 40 stearate, polyoxyl 50 stearate, polyoxyl 100 stearate, polyoxyl 12 distearate, polyoxyl 32 distearate, polyoxyl 150 distearate, or mixtures thereof.

35. The composition of claim 23, wherein the sugar ester surfactant is a sugar fatty acid monoester, a sugar fatty acid diester, or mixtures thereof.

36. The composition of claim 23, wherein the sugar ester surfactant comprises at least one saccharide unit.

37. The composition of claim 35, wherein the sugar fatty acid monoester, sugar fatty acid diester, or both, comprises sucrose.

38. The composition of claim 35, wherein the sugar fatty acid monoester sugar fatty acid diester, or both, comprises a fatty acid having from 6 to 24 carbon atoms.

39. The composition of claim 23, wherein the amount of solubilizing surfactant is between about 1% and 50% by weight of the composition.

40. The composition of claim 39, wherein the amount of solubilizing surfactant is between about 1% and 40% by weight of the composition.

41. The composition of claim 23, wherein the low solubility therapeutic agent is topiramate or salts or derivatives thereof

42. The composition of claim 23, wherein the low solubility therapeutic agent is released over a period of time ranging from about 1 hour to about 24 hours.

43. A composition comprising a low solubility therapeutic agent, a structural polymer and a solubilizing surfactant wherein the composition is a solid, and wherein said surfactant is selected from a polyoxyl stearate, poloxamer, sugar ester surfactant, or mixtures thereof.

44. A controlled release pharmaceutical composition comprising a low solubility therapeutic agent, a structural polymer and a solubilizing surfactant adapted to increase the solubility of the therapeutic agent, wherein said surfactant is selected from a polyoxyl stearate, poloxamer, sugar ester surfactant, or mixtures thereof.

45. A dosage form for controlled release of a therapeutic composition comprising a low solubility therapeutic agent, a structural polymer and a solubilizing surfactant, wherein said surfactant is selected from a polyoxyl stearate, poloxamer, sugar ester surfactant, or mixtures thereof.

46. The dosage form of claim 45, wherein the dosage form is a matrix system.

47. The dosage form of claim 45, wherein the dosage form is an osmotic system.

48. The dosage form of claim 45, wherein the dosage form is adapted to be administered once a day.

49. The dosage form of claim 45, which is adapted to release a high dose of the therapeutic agent.

50. The dosage form of claim 49, wherein the high dose of the therapeutic agent is between about 20% and about 90% by weight of the therapeutic composition.

51. The dosage form of claim 50, wherein the high dose of the therapeutic agent is between about 30% and about 40% by weight of the therapeutic composition.

52. The dosage form of claim 45, wherein the therapeutic agent is selected from topiramate, or salts or derivatives thereof.

53. A controlled release oral dosage form for once-a-day administration of a therapeutic agent comprising:

a. a core which comprises;

i. a low solubility therapeutic agent;

ii. a structural polymer;

iii. a solubilizing surfactant;

b. a semipermeable membrane surrounding the core; and

c. an exit orifice through the semipermeable membrane which communicates with the core so as to allow release of the therapeutic agent to the environment;

wherein the dosage form releases the therapeutic agent over a prolonged period of time, and wherein said surfactant is selected from a polyoxyl stearate, poloxamer, sugar ester surfactant, or mixtures thereof.

54. The controlled release oral dosage form of claim 53, adapted to release the therapeutic agent at a substantially zero order release rate or at a substantially ascending release rate.

55. The controlled release oral dosage form of claim 53, adapted to release the therapeutic agent with a pulsatile release profile or a pulsatile release profile after a delay.

56. The controlled release dosage form of claim 54, wherein the dosage form releases the therapeutic agent after a delay.

57. The controlled release dosage form of claim 53, wherein the therapeutic agent is topiramate or salts or derivatives thereof.

58. A method for delivering high doses of low solubility therapeutic agents comprising orally administering the dosage form of claim 53 to a subject.

59. A method for enhancing the bioavailability of a poorly soluble therapeutic agent comprising orally administering the dosage form of claim 53 to a subject.

60. The method of claim 58, wherein said therapeutic agent is topiramate or salts or derivatives thereof.

61. The method of claim 59, wherein said therapeutic agent is topiramate or salts or derivatives thereof.