Drug and excipient aerosol compositions

• US 20070286816A1
• Filed: 05/04/2007
• Published: 12/13/2007
• Est. Priority Date: 05/24/2001
• Status: Abandoned Application

• Current Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Original Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Inventors: Lu, Amy, Hale, Ron, Rabinowitz, Joshua, Myers, Daniel, Zaffaroni, Alejandro
• Application Number:
  US11/744,799
• Publication Number:
  US 20070286816A1
• Time in Patent Office: Days
• US Class Current: 424/45
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/5415 ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
• CPC Class Codes: A61K 31/5517 condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
• 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 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/007 Pulmonary tract; Aromatherapy
• CPC Class Codes: A61K 9/0078 for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
• CPC Class Codes: A61K 9/12 Aerosols; Foams A61K9/0043, A61K9/0056, A61K9/006, A61K9/0073 take precedence; spray-films A61K9/7015
• CPC Class Codes: A61M 11/002 by flow deviation causing inertial separation of transported particles
• CPC Class Codes: A61M 11/005 using ultrasonics spraying or atomising liquids using ultrasonic vibrations in general B05B17/06
• CPC Class Codes: A61M 11/04 operated by the vapour pressure of the liquid to be sprayed or atomised air-humidification, e.g. "room humidifiers" F24F6/00
• 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
• CPC Class Codes: A61M 15/00 Inhalators drug delivery in endotracheal tubes A61M16/04
• CPC Class Codes: A61M 2207/00 Methods of manufacture, assembly or production
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia

Abstract

The present invention provides novel condensation aerosols for the treatment of disease and/or intermittent or acute conditions. These condensation aerosols have little or no pyrolysis degradation products and are characterized by having an MMAD of between 1-3 microns. These aerosols are made by rapidly heating a substrate coated with a thin film of drug having a thickness of between 0.05 and 20 μm, while passing a gas over the film, to form particles of a desirable particle size for inhalation. Kits comprising a drug and a device for producing a condensation aerosol are also provided. The device contained in the kit typically, has an element for heating the drug which is coated as a film on the substrate and contains a therapeutically effective dose of a drug when the drug is administered in aerosol form, and an element allowing the vapor to cool to form an aerosol. Also disclosed, are methods for using these aerosols and kits.

Claims

1. An aerosol generation device, comprising:

a. a heatable filament; and

b. a composition coating the filament comprising a vaporizable carrier and a therapeutic agent;

wherein when the filament is heated to at least the vaporization point of the carrier, the carrier vaporizes and releases the therapeutic agent from the composition to thereby form an aerosol comprising the therapeutic agent and the carrier.

2. The aerosol generation device of claim 1, wherein the heatable filament is comprised of a coiled metal, a coiled semi-conductive, a coiled ceramic material, a coiled thermo-electric polymer, or a combination thereof.

3. The aerosol generation device of claim 2, wherein the heatable coiled filament is comprised of a metal selected from the group consisting of nickel chrome, tungsten, stainless steel, aluminum, and titanium.

4. The aerosol generation device of claim 2, wherein the aerosol generation device further comprises a power source for applying an electrical current to the heatable coiled filament.

5. The aerosol generation device of claim 1, wherein the heatable filament comprises a plurality of heatable filaments.

6. The aerosol generation device of claim 5, wherein the plurality of filaments are arranged in parallel relation to one another and are affixed at an end to a substrate.

7. The aerosol generation device of claim 1, wherein the composition further comprises a co-solvent.

8. The aerosol generation device of claim 7, wherein the co-solvent is selected from the group consisting of an alcohol, an aldehyde, a ketone, dimethyl sulfoxide, water, and combinations thereof.

9. The aerosol generation device of claim 1, wherein the therapeutic agent forms a coating over at least a portion of an outer layer of the carrier.

10. The aerosol generation device of claim 1, wherein the therapeutic agent and the carrier are intermixed in the composition.

11. The aerosol generation device of claim 1, wherein the carrier is selected from the group consisting of capric acid, lauric acid, oleic acid, palmitic acid, stearic acid, phosphatidyl cholines (PC), polyethylene glycol (PEG), polyvinylpyrrolidone, lysine, leucine, polylysine, polyleucine, and combinations thereof.

12. The aerosol generation device of claim 1, wherein the therapeutic agent comprises a small molecule, a polynucleotide, a polypeptide, or a recombinant virus.

13. The aerosol generation device of claim 12, wherein the therapeutic agent comprises a polynucleotide encoding a cystic fibrosis transmembrane conductance regulator polypeptide.

14. The aerosol generation device of claim 12, wherein the therapeutic agent comprises a recombinant virus comprising a polynucleotide encoding a cystic fibrosis transmembrane conductance regulator polypeptide.

15. A metered dose inhaler comprising the aerosol generation device of claim 1 for use in pulmonary delivery of the therapeutic agent to a subject.

16. A rodent nose-only exposure chamber comprising the aerosol generation device of claim 1 for use in pulmonary delivery of the therapeutic agent to a rodent subject.

17. The exposure chamber of claim 16, further comprising an elutriator positioned in flow communication between the aerosol generation device and the exposure chamber.

18. An aerosol generation device, comprising:

a. a heating element having a surface; and

b. a composition coating at least a portion of the heating element surface and comprising a carrier and a therapeutic agent;

wherein when the heating element surface is heated to at least the vaporization point of the carrier, the carrier vaporizes and releases the therapeutic agent from the composition to thereby form an aerosol comprising the therapeutic agent and the carrier.

19. The aerosol generation device of claim 18, wherein the heating element comprises a heatable filament.

20. The aerosol generation device of claim 18, wherein the heatable filament is comprised of a coiled metal, a coiled semi-conductive material, a coiled ceramic material, a coiled thermo-electric polymer, or a combination thereof.

21. The aerosol generation device of claim 20, wherein the heatable filament is comprised of a metal selected from the group consisting of nickel chrome, tungsten, stainless steel, aluminum, and titanium.

22. The aerosol generation device of claim 19, wherein the aerosol generation device further comprises a power source for applying an electrical current to the heatable filament.

23. The aerosol generation device of claim 19, wherein the heatable filament comprises a plurality of heatable filaments.

24. The aerosol generation device of claim 23, wherein the plurality of filaments are arranged in parallel relation to one another and are affixed at an end to a substrate.

25. The aerosol generation device of claim 18, wherein the composition further comprises a co-solvent.

26. The aerosol generation device of claim 25, wherein the co-solvent is selected from the group consisting of an alcohol, an aldehyde, a ketone, dimethyl sulfoxide, water, and combinations thereof.

27. The aerosol generation device of claim 18, wherein the therapeutic agent forms a coating over at least a portion of an outer layer of the carrier.

28. The aerosol generation device of claim 18, wherein the therapeutic agent and the carrier are intermixed in the composition.

29. The aerosol generation device of claim 18, wherein the carrier has a vaporization temperature that is less than the vaporization temperature of the therapeutic agent.

30. The aerosol generation device of claim 18, wherein the carrier has a vaporization temperature that is less than 500°

C.

31. The aerosol generation device of claim 18, wherein the carrier is selected from the group consisting of capric acid, lauric acid, oleic acid, palmitic acid, stearic acid, phosphatidyl cholines (PC), polyethylene glycol (PEG), polyvinylpyrrolidone, lysine, leucine, polylysine, polyleucine, and combinations thereof.

32. The aerosol generation device of claim 18, wherein the therapeutic agent comprises a small molecule, a polynucleotide, a polypeptide, or a recombinant virus.

33. The aerosol generation device of claim 32, wherein the therapeutic agent comprises a polynucleotide encoding a cystic fibrosis transmembrane conductance regulator polypeptide.

34. The aerosol generation device of claim 32, wherein the therapeutic agent comprises a recombinant virus comprising a polynucleotide encoding a cystic fibrosis transmembrane conductance regulator polypeptide.

35. A metered dose inhaler comprising the aerosol generation device of claim 18 for use in pulmonary delivery of the therapeutic agent to a subject.

36. A rodent nose-only exposure chamber comprising the aerosol generation device of claim 18 for use in pulmonary delivery of the therapeutic agent to a rodent subject.

37. The exposure chamber of claim 36, further comprising an elutriator positioned in flow communication between the aerosol generation device and the exposure chamber.

38. A method of producing an aerosol, comprising:

a. providing an aerosol generation device comprising;

i. a heating element having a surface; and

ii. a composition coating at least a portion of the heating element surface, the composition comprising a carrier and a therapeutic agent;

b. heating the surface of the heating element to vaporize the carrier and produce a heated vapor of the carrier and the therapeutic agent, thereby propelling the therapeutic agent from the surface of the heating element; and

c. cooling the vapor to condense the carrier and the compound into an aerosol.

39. The method of claim 38, wherein the heating element comprises a heatable filament.

40. The method of claim 39, wherein the heatable filament is comprised of a coiled metal, a coiled semi-conductive material, a coiled ceramic material, a coiled thermo-electric polymer, or a combination thereof.

41. The method of claim 40, wherein the heatable filament is comprised of a metal selected from the group consisting of nickel chrome, tungsten, stainless steel, aluminum, and titanium.

42. The method of claim 38, wherein the heatable filament comprises a plurality of heatable filaments.

43. The method of claim 38, wherein the composition further comprises a co-solvent.

44. The method of claim 43, wherein the co-solvent is selected from the group consisting of an alcohol, an aldehyde, a ketone, dimethyl sulfoxide, water, and combinations thereof.

45. The method of claim 38, wherein the therapeutic agent forms a coating over at least a portion of an outer layer of the carrier.

46. The method of claim 38, wherein the therapeutic agent and the carrier are intermixed in the composition.

47. The method of claim 38, wherein the carrier has a vaporization temperature that is less than the vaporization temperature of the therapeutic agent.

48. The method of claim 38, wherein the carrier has a vaporization temperature that is less than 500°

C.

49. The method of claim 38, wherein the carrier is selected from the group consisting of capric acid, lauric acid, oleic acid, palmitic acid, stearic acid, phosphatidyl cholines (PC), polyethylene glycol (PEG), polyvinylpyrrolidone, lysine, leucine, polylysine, polyleucine, and combinations thereof.

50. The method of claim 38, wherein the therapeutic agent comprises a small molecule, a polynucleotide, a polypeptide, or a recombinant virus.

51. The method of claim 50, wherein the therapeutic agent comprises a polynucleotide encoding a cystic fibrosis transmembrane conductance regulator polypeptide.

52. The method of claim 50, wherein the therapeutic agent comprises a recombinant virus comprising a polynucleotide encoding a cystic fibrosis transmembrane conductance regulator polypeptide.

53. The method of claim 38, wherein heating the surface of the heating element is by resistive heating of the heating element.

54. The method of claim 38, wherein heating the surface of the heating element is rapid.

55. The method of claim 38, wherein cooling the vapor is by exposure of the vapor to ambient air.

56. A method of administering a respiratory therapeutic agent to a subject comprising administering the aerosol of claim 38 to the subject.