Solid dose delivery vehicle and methods of making same

• US 7,785,631 B2
• Filed: 05/20/2005
• Issued: 08/31/2010
• Est. Priority Date: 12/02/1994
• Status: Expired due to Fees

• Current Assignee: Quadrant Drug Delivery Limited (Vectura Group Ltd.)
• Original Assignee: Quadrant Drug Delivery Limited (Vectura Group Ltd.)
• Inventors: Roser, Bruce J., Blair, Julian, Kampinga, Jaap, Colaco, Camilo
• Primary Examiner(s): Azpuru; Carlos A
• Application Number:
  US11/134,700
• Publication Number:
  US 20050276846A1
• Time in Patent Office: 1,929 Days
• Field of Search: 424/489, 424/499
• US Class Current: 424/499
• 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 therapeutic composition is a powder comprising therapeutic particles having a particle size distribution suitable for pulmonary administration,

c) the therapeutic particles are in a glassy state,

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

e) the carbohydrate is selected from the group consisting of monosaccharides, disaccharides and sugar alcohols,

f) the therapeutic particles remain in the glassy state when stored at elevated temperature, wherein the elevated temperature is 60°

C.,

g) the protein is distributed homogeneously and in solid solution in the carbohydrate, and

h) the therapeutic particles have a mean particle size of 0.5 to 5 μ

m.

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

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

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

m.

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

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

7. The therapeutic composition according to claim 6, wherein the therapeutic particles have a mean particle size of 1 to 4 μ

m.

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

9. The therapeutic composition according to claim 8, wherein the therapeutic particles have a mean particle size of 1 to 4 μ

m.

10. The therapeutic composition according to claim 1, the therapeutic particles further comprising an amino acid that is capable of inhibiting the Maillard reaction.

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

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

27. The therapeutic composition according to claim 1, wherein the protein is insulin and the carbohydrate is a sugar alcohol.

28. The therapeutic composition according to claim 1 or 27, wherein the therapeutic particles remain in a glassy state at 70°

C.

29. The therapeutic composition according to claim 28, said therapeutic particles further comprising a glass modifier, wherein the glass modifier is not the bioactive material.

30. The therapeutic composition according to claim 28, said therapeutic particles further comprising an amino acid that is capable of inhibiting the Maillard reaction.

31. The therapeutic composition according to claim 28, said therapeutic particles further comprising a physiologically acceptable inhibitor of the Maillard reaction.

32. The therapeutic composition according to claim 28, wherein the composition is suitable for transalveolar administration.

33. The therapeutic composition according to claim 1, wherein the therapeutic particles remain in the glassy state when stored at elevated temperature for one month.

34. The therapeutic composition according to claim 33, said therapeutic particles further comprising a glass modifier, wherein the glass modifier is not the bioactive material.

35. The therapeutic composition according to claim 33, said therapeutic particles further comprising an amino acid that is capable of inhibiting the Maillard reaction.

36. The therapeutic composition according to claim 33, wherein the therapeutic particles remain in the glassy state at 70°

C.

37. The therapeutic composition according to claim 36, said therapeutic particles further comprising a glass modifier, wherein the glass modifier is not the bioactive material.

38. The therapeutic composition according to claim 36, said therapeutic particles further comprising an amino acid that is capable of inhibiting the Maillard reaction.

39. The therapeutic composition according to claim 1, wherein the carbohydrate is a disaccharide.

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

41. The therapeutic composition according to claim 39 or 40, said therapeutic particles further comprising a glass modifier, wherein the glass modifier is not the bioactive material.

42. The therapeutic composition according to claim 39 or 40, said therapeutic particles further comprising an amino acid that is capable of inhibiting the Maillard reaction.

43. The therapeutic composition according to claim 39 or 40, wherein the therapeutic particles remain in the glassy state at 70°

C.

44. The therapeutic composition according to claim 39 or 40, wherein the therapeutic particles remain in the glassy state when stored at elevated temperature for one month.

45. The therapeutic composition according to claim 3, wherein the biodegradable glass is a water soluble glass.

46. The therapeutic composition according to claim 45, wherein the protein is insulin.

47. The therapeutic composition according to claim 45, wherein the carbohydrate is a sugar alcohol.

48. The therapeutic composition according to claim 45 or 46 or 47, wherein the composition is suitable for transalveolar administration.

49. The therapeutic composition according to claim 48, wherein the therapeutic particles remain in the glassy state when stored at 60°

C. for one month.

50. The therapeutic composition according to claim 49, said therapeutic particles further comprising a physiologically acceptable inhibitor of the Maillard reaction.

51. The therapeutic composition according to claim 45 or 46 or 47, wherein the therapeutic particles remain in the glassy state when stored at 60°

C. for one month.

52. The therapeutic composition according to claim 45 or 46 or 47, said therapeutic particles further comprising a physiologically acceptable inhibitor of the Maillard reaction.

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

a) the bioactive material is a protein,

b) the therapeutic composition comprises therapeutic particles in a glassy state,

c) the therapeutic composition is a powder having a particle size distribution suitable for pulmonary administration,

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

e) the therapeutic particles further comprise a glass modifier, wherein the glass modifier is not the bioactive material,

f) the carbohydrate is selected from the group consisting of monosaccharides, disaccharides and sugar alcohols,

g) the therapeutic particles remain in the glassy state when stored at elevated temperature, wherein the elevated temperature is 60°

C.,

h) the protein is distributed homogeneously and in solid solution in the carbohydrate, and

i) the particles have a mean particle size of 0.5 to 5 μ

m.

14. The therapeutic composition according to claim 13, wherein the glass modifier is a protein.

15. The therapeutic composition according to claim 13, said therapeutic particles further comprising a physiologically acceptable inhibitor of the Maillard reaction.

16. The therapeutic composition according to claim 13, said therapeutic particles further comprising a biodegradable glass.

17. The therapeutic composition according to claim 13, wherein the therapeutic particles have a mean particle size of 1 to 4 μ

m.

18. The therapeutic composition according to claim 13, wherein the carbohydrate is a sugar alcohol.

19. The therapeutic composition according to claim 13, wherein the carbohydrate is trehalose.

20. The therapeutic composition according to claim 13, wherein the protein is insulin.

21. The therapeutic composition according to claim 20, wherein the therapeutic particles have a mean particle size of 1 to 4 μ

m.

22. The therapeutic composition according to claim 13, wherein the protein is insulin and the carbohydrate is trehalose.

23. The therapeutic composition according to claim 22, wherein the therapeutic particles have a mean particle size of 1 to 4 μ

m.

24. The therapeutic composition according to claim 13, said therapeutic particles further comprising an amino acid that is capable of inhibiting the Maillard reaction.

25. The therapeutic composition according to claim 13, wherein the bioactive material is stabilized for storage at elevated temperature for one month.

26. The therapeutic composition according to claim 13, wherein the therapeutic composition is suitable for delivering the bioactive material by transalveolar administration.