Solid dose delivery vehicle and methods of making same

• US 20050276846A1
• Filed: 05/20/2005
• Published: 12/15/2005
• Est. Priority Date: 12/02/1994
• Status: Active Grant

• Current Assignee: Quadrant Drug Delivery Limited (Vectura Group Ltd.)
• Original Assignee: Quadrant Drug Delivery Limited (Vectura Group Ltd.)
• Inventors: Colaco, Camilo, Roser, Bruce J., Blair, Julian, Kampinga, Jaap
• Granted Patent: US 7,785,631 B2
• Time in Patent Office: Days
• US Class Current: 424/464
• CPC Class Codes: A61K 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61K 9/1623 Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention encompasses a solid dose delivery vehicle for ballistic administration of a bioactive material to subcutaneous and intradermal tissue, the delivery vehicle being sized and shaped for penetrating the epidermis. The delivery vehicle further comprises a stabilizing polyol glass loaded with the bioactive material and capable of releasing the bioactive material in situ. The present invention further includes methods of making and using the solid dose delivery vehicle of the invention.

Claims

1. A therapeutic composition in solid dose form comprising a bioactive material and a carbohydrate, wherein

a) the bioactive material is a protein,

b) the carbohydrate stabilizes the bioactive material for storage at elevated temperature,

c) the therapeutic composition is in a glassy state,

d) the therapeutic composition is a powder suitable for pulmonary administration, and

e) the bioactive material and the carbohydrate are dispersed within particles of the powder.

2. The therapeutic composition according to claim 1, further comprising a physiologically acceptable inhibitor of the Maillard reaction.

3. The therapeutic composition according to claim 1, further comprising a biodegradable glass.

4. The therapeutic composition according to claim 1, wherein the particles have a mean particle size of 0.1 to 10 μ

m.

5. The therapeutic composition according to claim 1, wherein the particles have a mean particle size of 0.5 to 5 μ

m.

6. The therapeutic composition according to claim 1, wherein the particles have a mean particle size of 1 to 3 μ

m.

7. The therapeutic composition according to claim 1, wherein the carbohydrate is selected from the group consisting of monosaccharides, disaccharides, trisaccharides, oligosaccharides, and sugar alcohols.

8. The therapeutic composition according to claim 1, wherein the carbohydrate is a sugar alcohol.

9. The therapeutic composition according to claim 1, wherein the carbohydrate is trehalose.

10. The therapeutic composition according to claim 1, wherein the protein is an enzyme.

11. The therapeutic composition according to claim 1, wherein the protein is a hormone.

12. The therapeutic composition according to claim 1, wherein the protein is a growth factor.

13. The therapeutic composition according to claim 1, wherein the protein is an immunogen.

14. The therapeutic composition according to claim 1, wherein the protein is a monoclonal antibody.

15. The therapeutic composition according to claim 1, wherein the protein is an interferon.

16. The therapeutic composition according to claim 1, wherein the protein is an interleukin.

17. The therapeutic composition according to claim 1, wherein the protein is a cytokine.

18. The therapeutic composition according to claim 1, wherein the protein is insulin.

19. The therapeutic composition according to claim 18, wherein the particles have a mean particle size of 0.5 to 5 μ

m.

20. The therapeutic composition according to claim 18, wherein the particles have a mean particle size of 1 to 3 μ

m.

21. The therapeutic composition according to claim 18, wherein the insulin and the carbohydrate are in solid solution.

22. The therapeutic composition according to claim 1, wherein the protein is insulin and the carbohydrate is trehalose.

23. The therapeutic composition according to claim 22, wherein the particles have a mean particle size of 0.5 to 5 μ

m.

24. The therapeutic composition according to claim 22, wherein the particles have a mean particle size of 1 to 3 μ

m.

25. The therapeutic composition according to claim 22, wherein the insulin and the trehalose are in solid solution.

26. The therapeutic composition according to claim 1, further comprising an amino acid.

27. The therapeutic composition according to claim 1, wherein the elevated temperature is 60°

C.

28. The therapeutic composition according to claim 1, wherein the bioactive material is stabilized for storage at elevated temperature for at least one month.

29. The therapeutic composition according to claim 1, wherein the bioactive material and the carbohydrate are in solid solution.

30. The therapeutic composition according to claim 1, wherein the therapeutic composition is suitable for delivering the bioactive material by transalveolar administration.

31. A therapeutic composition in solid dose form comprising a bioactive material and a carbohydrate, wherein

a) the bioactive material is a protein,

b) the carbohydrate stabilizes the bioactive material for storage at elevated temperature,

c) the therapeutic composition is in a glassy state,

d) the therapeutic composition is a powder suitable for pulmonary administration,

e) the bioactive material and the carbohydrate are dispersed within particles of the powder, and

f) the therapeutic composition further comprises a glass modifier, wherein the glass modifier is not the bioactive material.

32. The therapeutic composition according to claim 31, wherein the glass modifier is a protein.

33. The therapeutic composition according to claim 31, further comprising a physiologically acceptable inhibitor of the Maillard reaction.

34. The therapeutic composition according to claim 31, further comprising a biodegradable glass.

35. The therapeutic composition according to claim 31, wherein the particles have a mean particle size of 0.1 to 10 μ

m.

36. The therapeutic composition according to claim 31, wherein the particles have a mean particle size of 0.5 to 5 μ

m.

37. The therapeutic composition according to claim 31, wherein the particles have a mean particle size of 1 to 3 μ

m.

38. The therapeutic composition according to claim 31, wherein the carbohydrate is selected from the group consisting of monosaccharides, disaccharides, trisaccharides, oligosaccharides, and sugar alcohols.

39. The therapeutic composition according to claim 31, wherein the carbohydrate is a sugar alcohol.

40. The therapeutic composition according to claim 31, wherein the carbohydrate is trehalose.

41. The therapeutic composition according to claim 31, wherein the protein is an enzyme.

42. The therapeutic composition according to claim 31, wherein the protein is a hormone.

43. The therapeutic composition according to claim 31, wherein the protein is a growth factor.

44. The therapeutic composition according to claim 31, wherein the protein is an immunogen.

45. The therapeutic composition according to claim 31, wherein the protein is a monoclonal antibody.

46. The therapeutic composition according to claim 31, wherein the protein is an interferon.

47. The therapeutic composition according to claim 31, wherein the protein is an interleukin.

48. The therapeutic composition according to claim 31, wherein the protein is a cytokine.

49. The therapeutic composition according to claim 31, wherein the protein is insulin.

50. The therapeutic composition according to claim 49, wherein the particles have a mean particle size of 0.5 to 5 μ

m.

51. The therapeutic composition according to claim 49, wherein the particles have a mean particle size of 1 to 3 μ

m.

52. The therapeutic composition according to claim 49, wherein the insulin and the carbohydrate are in solid solution.

53. The therapeutic composition according to claim 31, wherein the protein is insulin and the carbohydrate is trehalose.

54. The therapeutic composition according to claim 53, wherein the particles have a mean particle size of 0.5 to 5 μ

m.

55. The therapeutic composition according to claim 53, wherein the particles have a mean particle size of 1 to 3 μ

m.

56. The therapeutic composition according to claim 53, wherein the insulin and the trehalose are in solid solution.

57. The therapeutic composition according to claim 31, further comprising an amino acid.

58. The therapeutic composition according to claim 31, wherein the elevated temperature is 60°

C.

59. The therapeutic composition according to claim 31, wherein the bioactive material is stabilized for storage at elevated temperature for at least one month.

60. The therapeutic composition according to claim 31, wherein the bioactive material and the carbohydrate are in solid solution.

61. The therapeutic composition according to claim 31, wherein the therapeutic composition is suitable for delivering the bioactive material by transalveolar administration.