Substrates for drug delivery device and methods of preparing and use

• US 20050034723A1
• Filed: 08/04/2004
• Published: 02/17/2005
• Est. Priority Date: 08/04/2003
• Status: Abandoned Application

• Current Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Original Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Inventors: Hale, Ron L., Rabinowitz, Joshua D., Myers, Daniel J., Lu, Amy, Sharma, Krishnamohan, Bennett, Bryson
• Application Number:
  US10/912,417
• Publication Number:
  US 20050034723A1
• Time in Patent Office: Days
• US Class Current: 128/203.120
• CPC Class Codes: A61K 31/553 having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
• CPC Class Codes: A61K 9/00 Medicinal preparations characterised by special physical form nuclear magnetic resonance contrast preparations or magnetic resonance imaging contrast preparations A61K49/18; preparations containing radioactive substances A61K51/12
• CPC Class Codes: A61K 9/007 Pulmonary tract; Aromatherapy
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61M 11/001 Particle size control
• CPC Class Codes: A61M 11/041 using heaters
• CPC Class Codes: A61M 11/042 electrical
• CPC Class Codes: A61M 11/047 by exothermic chemical reaction

Abstract

An assembly and method for producing a condensation aerosol are disclosed. The assembly includes a heat-conductive metal substrate with an oxidation resistant exterior surface and a drug composition film on the exterior surface and is for use in an aerosol device. The thickness of the film and the surface of the substrate is such that the aerosol formed by vaporizing and condensing the drug composition the aerosol contain 10% by weight or less drug-degradation products and at least 50% of the total amount of the drug composition in the film. The methods for treating the exterior surface include heat and chemical treatment and formation of a protective overcoat.

Claims

1. A drug-supply assembly comprising:

a heat conductive substrate;

a non-reactive exterior surface on the heat conductive substrate; and

a film comprising a compound on the non-reactive exterior surface.

2. The drug-supply assembly of claim 1, wherein the heat conductive substrate is a metal.

3. The drug-supply assembly of claim 2, wherein the metal is selected from the group consisting of steel, stainless steel, aluminum, chromium, copper, iron, and titanium.

4. The drug-supply assembly of claim 3, wherein the stainless steel is selected from the group consisting of an austenitic alloy, a ferritic alloy, or a combination thereof.

5. The drug-supply assembly of claim 2, wherein the metal is treated to generate a non-reactive metal species on a surface of the substrate.

6. The drug-supply assembly of claim 5, wherein the metal is treated by heating the metal and the non-reactive metal species comprises oxidized metal.

7. The drug-supply assembly of claim 6, wherein the oxidized metal is selected from the group consisting of iron oxide, chromium oxide, nickel oxide, molybdenum oxide, silicon oxide and aluminum oxide.

8. The drug-supply assembly of claim 5, wherein the metal is treated by chemicals and the non-reactive metal species comprises oxidized metal.

9. The drug-supply assembly of claim 8, wherein the oxidized metal is selected from the group consisting of iron oxide, chromium oxide, and aluminum oxide.

10. The drug-supply assembly of claim 1, wherein the non-reactive exterior surface comprises an oxidized metal layer on the substrate.

11. The drug-supply assembly of claim 1, wherein the non-reactive exterior surface comprises zirconium oxide, aluminum oxide, silicon oxide, silicon carbide an inert metal, or a combination thereof.

12. The drug-supply assembly of claim 11, wherein the inert metal is gold and/or platinum.

13. The drug-supply assembly of claim 1, further comprising a heating element in thermal communication with the heat conductive substrate.

14. The drug-supply assembly of claim 13, wherein the heating element supplies heat to the substrate to produce a substrate temperature of at least about 250°

C.

15. The drug-supply assembly of claim 14, wherein the substrate temperature is sufficient to volatilize the film from the non-reactive exterior surface.

16. The drug-supply assembly of claim 1, wherein the film comprises a drug.

17. The drug-supply assembly of claim 1, wherein the film is about 0.05 to 20 microns thick.

18. The drug-supply assembly of claim 16, wherein the film comprises a therapeutically effective amount of drug upon vaporization.

19. A condensation aerosol device comprising the drug-supply assembly of claim 1.

20. An assembly for use in a condensation aerosol device comprising

(a) a heat-conductive metal substrate having an oxidation resistant exterior surface, and

(b) a drug composition film on the exterior surface, where the film thickness and exterior surface are such that an aerosol formed by vaporizing the drug composition by heating the substrate and condensing the vaporized drug composition contains 10% by weight or less drug-degradation products and at least 50% of the total amount of the drug composition in the film.

21. The assembly of claim 20, further comprising a heat source for supplying heat to said substrate to produce a substrate temperature greater than 250°

C. and to substantially volatilize the drug composition film from the substrate in a period of 2 seconds or less.

22. The assembly of claim 20, wherein the film comprises a thickness between 0.05 and 20 microns.

23. The assembly of claim 20, wherein the film comprises a therapeutically effective dose of a drug when the drug is administered in aerosol form.

24. The assembly of claim 20, wherein the heat conductive metal substrate comprises steel, aluminum, titanium or copper.

25. The assembly of claim 20, wherein the heat conductive metal substrate is oxidatively and/or chemically less reactive at temperatures over 300°

C.

26. The assembly of claim 20, wherein the oxidation resistant exterior surface is metal oxide-enriched and comprises silicon oxide, iron oxide, chromium oxide, molybdenum oxide, manganese oxide, titanium oxide and/or aluminum oxide.

27. The assembly of claim 20, wherein the oxidation resistant exterior surface comprises a protective overcoat of a material selected from the group consisting of zirconium oxide, silicon oxide, aluminum oxide, aluminum nitride, and silicon carbide.

28. The assembly of claim 20, wherein the oxidation resistant surface is a protective overcoat of an inert metal.

29. The assembly of claim 28, wherein the inert metal is gold and/or platinum.

30. The assembly of claim 20, wherein when a drug composition film is vaporized and condensed to form aerosol particles, under selected conditions that lead to at least 50% recovery of drug composition in the aerosol, the aerosol produced exhibits (i) less than about 10% by weight drug degradation products and (ii) increased levels of drug degradation products when the substrate surface is not a metal-oxide enriched substrate surface.

31. A drug-supply assembly made by a process comprising:

treating an exterior surface of a heat-conductive substrate to increase the oxidation resistance of the exterior surface; and

coating at least a portion of the oxidized exterior surface of the substrate with a compound to generate a film.

32. The drug-supply assembly of claim 31, wherein the heat-conductive substrate is a metal substrate.

33. The drug-supply assembly of claim 31, wherein the treating is by contacting the metal substrate with a chemical that oxidizes that exterior surface.

34. The drug-supply assembly of claim 31, wherein the treating is by heating the metal substrate to oxidize the exterior surface.

35. The drug-supply assembly of claim 31, wherein the exterior surface is treated with an overcoat of an oxidation resistant material.

36. The drug-supply assembly of claim 35, wherein the overcoat is formed by physical vapor deposition, chemical vapor deposition, Electron Beam Deposition, sputtering, ion assisted depositions, electroplating, dip coating, spray coating, and/or sol-gel deposition.

37. The drug-supply assembly of claim 33, wherein the chemical is an acid.

38. The drug-supply assembly of claim 33, wherein the chemical is a base.

39. The drug-supply assembly of claim 34, wherein the heating is at 350°

C. for 6 hours.

40. A method of making a drug-supply assembly comprising:

treating an exterior surface of a heat-conductive substrate to increase the oxidation resistance of the exterior surface; and

coating at least a portion of the oxidized exterior surface of the substrate with a compound to generate a film.

41. The method of claim 40, wherein the heat-conductive substrate is a metal substrate.

42. The method of claim 40, wherein the treating is by contacting the metal substrate with a chemical that oxidizes that exterior surface.

43. The method of claim 40, wherein the treating is by heating the metal substrate to oxidize the exterior surface.

44. The method of claim 40, wherein the exterior surface is treated with an overcoat of an oxidation resistant material.

45. The method of claim 44, wherein the overcoat is formed by physical vapor deposition, chemical vapor deposition, Electron Beam Deposition, sputtering, ion assisted depositions, electroplating, dip coating, spray coating, and/or sol-gel deposition.

46. The method of claim 42, wherein the chemical is an acid.

47. The method of claim 42, wherein the chemical is a base.

48. The method of claim 43, wherein the heating is at 350°

C. for 6 hours.

49. A drug-supply assembly made by the method of claim 40.

50. A method of increasing the purity of drug condensation particles in a condensation drug aerosol that is produced by substantially vaporizing and condensing a drug film on a substrate comprising substantially vaporizing a drug composition on an oxide-enriched metal substrate and condensing the vapor to form drug particles.