Drug Delivery System for Retarding Release of Water Soluble Drugs

Abstract

An implantable drug delivery system uses a hydrophobic compound as an outer layer or barrier for retarding release of water soluble drugs from the implantable system. The system includes an inner portion of a water soluble drug in a drug matrix material which stabilizes the drug. An outer portion of the drug delivery system separates the inner portion from a surrounding environment. The outer portion retards the release of the water soluble drug from the inner portion. The outer portion includes a hydrophobic non-polymer compound and a binder. The hydrophobic compound can be another drug which can be delivered at an entirely different release kinetic from the water soluble drug and for treatment of the same or a different condition. When the drug delivery system is implanted in a body the outer portion retards the release of the water soluble drug by controlling fluid passing from the body into the inner portion and by controlling passage of the water soluble drug from the inner portion into the body.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will now be described in greater detail with reference to the preferred embodiments illustrated in the accompanying drawings, in which like elements bear like reference numerals, and wherein:

FIG. 1 is a perspective view of one example of a stent according to the present invention.

FIG. 2 is a side view of a portion of the stent of FIG. 1.

FIG. 3 is a side cross sectional view of an example of an opening in a medical device showing a drug delivery system within a reservoir in the medical device.

FIGS. 4 a and 4b are graphs of the release curves for insulin and Pimecrolimus from the dual drug stent described in Example 1.

FIGS. 5 a and 5b are graphs of the release curves for insulin and Pimecrolimus from the dual drug stent described in Example 2.

FIGS. 6 a and 6b are graphs of the release curves for insulin and Pimecrolimus from the dual drug stent described in Example 3.

FIGS. 7 a and 7b are graphs of the release curves for insulin and Pimecrolimus from the dual drug stent described in Example 4.

FIGS. 8 a and 8b are graphs of the release curves for insulin and Pimecrolimus from the dual drug stent described in Example 5.

FIGS. 9 a and 9b are graphs of the release curves for insulin and Pimecrolimus from the dual drug stent described in Example 6.

Claims

1. An implantable drug delivery system for retarding release of water soluble drugs, the system comprising: an inner portion of the drug delivery system comprising a water soluble drug and a drug matrix material which stabilizes the drug; andan outer portion of the drug delivery system which retards the release of the water soluble drug from the inner portion, the outer portion comprising a hydrophobic non-polymer compound and less than 50% of a binder, wherein when the drug delivery system is implanted in a body the outer portion retards the release of the water soluble drug by controlling fluid passing from the body into the inner portion and by controlling passage of the water soluble drug from the inner portion into the body.

2. The system of claim 1, wherein the water soluble drug has a solubility in water of greater than 0.1 mg/ml.

3. The system of claim 2, wherein the water soluble drug is insulin.

4. The system of claim 2, wherein the water soluble drug is an antirestenotic.

5. The system of claim 2, wherein the water soluble drug is selected from the group of Angiomax, dipyridamole, imatinib mesylate, cladribine, heparin, aspirin, doxycycline, and doxycycline hyclate.

6. The system of claim 1, wherein the drug matrix material is hydrophilic.

7. The system of claim 1, wherein the drug matrix material is biodegradable.

8. The system of claim 7, wherein the drug matrix material is a polymer.

9. The system of claim 1, wherein the drug matrix material is a polymer.

10. The system of claim 9, wherein the drug matrix material is polylactic acid or a copolymer thereof.

11. The system of claim 10, wherein the drug matrix material is polylactic-co-glycolic acid.

12. The system of claim 1, wherein hydrophobic material is a drug.

13. The system of claim 12, wherein the drug is an antirestenotic drug.

14. The system of claim 13, wherein the drug is pimecrolimus, sirolimus, everolimus, ABT-578, or paclitaxel.

15. The system of claim 1, wherein the hydrophobic material has a calculated Log P or Log D value of at least one.

16. The system of claim 15, wherein the hydrophobic material is a drug.

17. The system of claim 15, wherein the hydrophobic material is a preservative or plasticizer.

18. The system of claim 1, wherein the hydrophobic material has a molecular weight of less than 3000.

19. The system of claim 18, wherein the hydrophobic material is a drug.

20. The system of claim 18, wherein the hydrophobic material is a preservative or a plasticizer.

21. The system of claim 1, wherein the outer portion comprises the hydrophobic material and less than 30% of the binder.

22. The system of claim 1, wherein the outer portion comprises the hydrophobic material and less than 10% of the binder.

23. The system of claim 12, wherein the outer portion comprises the hydrophobic material and less than 30% of the binder.

24. The system of claim 12, wherein the outer portion comprises the hydrophobic material and less than 10% of the binder.

25. A drug delivery stent comprising: an expandable stent structure having a plurality of reservoirs;a drug delivery system provided within the reservoirs of the stent structure, the drug delivery system having an inner portion and an outer portion;wherein the inner portion of the drug delivery system comprises a water soluble drug and a drug matrix material which stabilizes the drug; andwherein the outer portion of the drug delivery system retards the release of the water soluble drug from the inner portion, the outer portion comprising a hydrophobic non-polymer compound and of a binder at a ratio of less than 50% by weight of the binder, wherein when the stent is implanted in a body the outer portion retards the release of the water soluble drug by controlling fluid passing from the body into the inner portion and by controlling passage of the water soluble drug from the inner portion into the body.

26. The stent of claim 25, wherein the water soluble drug has a solubility in water of greater than 1 mg/ml.

27. The stent of claim 26, wherein the water soluble drug is insulin.

28. The stent of claim 26, wherein the water soluble drug is an antirestenotic.

29. The stent of claim 26, wherein the water soluble drug is selected from the group of Angiomax, dipyridamole, imatinib mesylate, cladribine, heparin, aspirin, doxycycline, and doxycycline hyclate.

30. The stent of claim 25, wherein the drug matrix material is hydrophilic.

31. The stent of claim 25, wherein the drug matrix material is biodegradable.

32. The stent of claim 31, wherein the drug matrix material is a polymer.

33. The stent of claim 25, wherein the drug matrix material is a polymer.

34. The stent of claim 33, wherein the drug matrix material is polylactic acid or a copolymer thereof.

35. The stent of claim 34, wherein the drug matrix material is polylactic-co-glycolic acid.

36. The stent of claim 25, wherein hydrophobic material is a drug.

37. The stent of claim 36, wherein the drug is an antirestenotic drug.

38. The stent of claim 37, wherein the drug is pimecrolimus, sirolimus, everolimus, ABT-578, or paclitaxel.

39. The stent of claim 25, wherein the hydrophobic material has a calculated Log P or Log D value of at least one.

40. The stent of claim 39, wherein the hydrophobic material is a drug.

41. The system of claim 39, wherein the hydrophobic material is a preservative or plasticizer.

42. The stent of claim 25, wherein the hydrophobic material has a molecular weight of less than 3000.

43. The stent of claim 42, wherein the hydrophobic material is a drug.

44. The stent of claim 42, wherein the hydrophobic material is a preservative or a plasticizer.

45. The stent of claim 25, wherein the outer portion forms a cap over the inner portion within the reservoir.

46. The stent of claim 45, wherein the inner portion and the outer portion are both formed entirely within the reservoirs.

47. The stent of claim 25, wherein the water soluble drug is insulin and the hydrophobic compound is an antirestenotic.

48. A drug delivery stent comprising: an expandable stent structure having a plurality of reservoirs; a drug delivery system provided within the reservoirs of the stent structure, the drug delivery system having an inner portion and an outer portion;wherein the inner portion of the drug delivery system comprises a water soluble drug and a drug matrix material which stabilizes the drug; andwherein the outer portion of the drug delivery system retards the release of the water soluble drug from the inner portion, the outer portion comprising a hydrophobic non-polymer compound and of a binder at a ratio of less than 50% by weight of the binder, wherein when the stent is implanted in a body the outer portion retards the release of the water soluble drug by controlling fluid passing from the body into the inner portion and by controlling passage of the water soluble drug from the inner portion into the body.

49. The stent of claim 48, wherein hydrophobic material is a drug.

50. The stent of claim 48, wherein the outer portion comprises the hydrophobic material and less than 30% of the binder.

51. The stent of claim 48, wherein the outer portion comprises the hydrophobic material and less than 10% of the binder.

52. A drug delivery stent comprising: an expandable stent structure;a drug delivery system secured to the stent structure, the drug delivery system having an inner portion and an outer portion; wherein the inner portion of the drug delivery system comprises a water soluble drug and a drug matrix material which stabilizes the drug; andwherein the outer portion of the drug delivery system retards the release of the water soluble drug from the inner portion, the outer portion comprising a hydrophobic non-polymer compound, wherein when the stent is implanted in a body the outer portion retards the release of the water soluble drug by controlling fluid passing from the body into the inner portion and by controlling passage of the water soluble drug from the inner portion into the body.

53. The stent of claim 52, wherein the water soluble drug is insulin.

54. The stent of claim 53, wherein hydrophobic material is a drug.

55. The stent of claim 54, wherein the drug is an antirestenotic drug.

56. The stent of claim 55, wherein the drug is pimecrolimus, sirolimus, everolimus, ABT-578, or paclitaxel.

57. The stent of claim 56, wherein the outer portion comprises the hydrophobic material and less than 30% of the binder.

58. The stent of claim 56, wherein the outer portion comprises the hydrophobic material and less than 10% of the binder.