Delivery of compounds for the treatment of headache through an inhalation route

• US 7,498,019 B2
• Filed: 03/21/2006
• Issued: 03/03/2009
• Est. Priority Date: 05/24/2001
• Status: Expired due to Fees

• 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., Solas, Dennis W., Zaffaroni, Alejandro C.
• Primary Examiner(s): Haghighatian; Mina
• Application Number:
  US11/385,992
• Publication Number:
  US 20060233717A1
• Time in Patent Office: 1,078 Days
• Field of Search: 424/45, 424/46, 424/489, 424/499, 424/434, 514/958, 128/200.14, 128/200.24, 128/203.15
• US Class Current: 424/45
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• 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

Abstract

The present invention relates to the delivery of migraine headache drugs through an inhalation route. Specifically, it relates to aerosols containing migraine headache drugs that are used in inhalation therapy.

Claims

1. A condensation aerosol for delivery of rizatriptan formed by heating a composition containing rizatriptan coated on a solid support to form a vapor and condensing the vapor to form a condensation aerosol comprising particles, wherein the particles comprise at least 10 percent by weight of rizatriptan and less than 5 percent by weight of rizatriptan degradation products, and the condensation aerosol has an MMAD of less than 5 microns.

2. The condensation aerosol according to claim 1, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns.

3. The condensation aerosol according to claim 1 or claim 2, wherein the geometric standard deviation around the MMAD is less than 3.0.

37. The condensation aerosol according to claim 2, wherein the condensing comprises allowing the vapor to cool.

4. A condensation aerosol for delivery of zolmitriptan formed by heating a composition containing zolmitriptan coated on a solid support to form a vapor and condensing the vapor to form a condensation aerosol comprising particles, wherein the particles comprise at least 10 percent by weight of zolmitriptan and less than 5 percent by weight of zolmitriptan degradation products, and the condensation aerosol has an MMAD of less than 5 microns.

5. The condensation aerosol according to claim 4, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns.

6. The condensation aerosol according to claim 4 or claim 5, wherein the geometric standard deviation around the MMAD is less than 3.0.

38. The condensation aerosol according to claim 5, wherein the condensing comprises allowing the vapor to cool.

7. A condensation aerosol for delivery of sumatriptan formed by heating a composition containing sumatriptan coated on a solid support to form a vapor and condensing the vapor to form a condensation aerosol comprising particles, wherein the particles comprise at least 10 percent by weight of sumatriptan and less than 5 percent by weight of sumatriptan degradation products, and the condensation aerosol has an MMAD of less than 5 microns.

8. The condensation aerosol according to claim 7, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns.

9. The condensation aerosol according to claim 7 or claim 8, wherein the geometric standard deviation around the MMAD is less than 3.0.

39. The condensation aerosol according to claim 8, wherein the condensing comprises allowing the vapor to cool.

10. A condensation aerosol for delivery of frovatriptan formed by heating a composition containing frovatriptan coated on a solid support to form a vapor and condensing the vapor to form a condensation aerosol comprising particles, wherein the particles comprise at least 10 percent by weight of rovatriptan and less than 5 percent by weight of frovatriptan degradation products, and the condensation aerosol has an MMAD of less than 5 microns.

11. The condensation aerosol according to claim 10, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns.

12. The condensation aerosol according to claim 10 or claim 11, wherein the geometric standard deviation around the MMAD is less than 3.0.

40. The condensation aerosol according to claim 11, wherein the condensing comprises allowing the vapor to cool.

13. A condensation aerosol for delivery of naratriptan formed by heating a composition containing naratriptan coated on a solid support to form a vapor and condensing the vapor to form a condensation aerosol comprising particles, wherein the particles comprise at least 10 percent by weight of naratriptan and less than 5 percent by weight of naratriptan degradation products, and the condensation aerosol has an MMAD of less than 5 microns.

14. The condensation aerosol according to claim 13, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns.

15. The condensation aerosol according to claim 13 or claim 14, wherein the geometric standard deviation around the MMAD is less than 3.0.

41. The condensation aerosol according to claim 14, wherein the condensing comprises allowing the vapor to cool.

16. A method of forming a rizatriptan containing aerosol comprising:

(a) heating a composition containing rizatriptan coated on a solid support to form a vapor; and

(b) condensing the vapor to form a condensation aerosol comprising particles,

wherein the particles comprise less than 5 percent by weight of rizatriptan degradation products, and the condensation aerosol has an MMAD of less than 5 microns.

17. The method according to claim 16, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns.

18. The method according to claim 17, wherein the coated composition comprises at least 10 percent by weight of rizatriptan.

42. The method according to claim 17, wherein the condensing comprises allowing the vapor to cool.

19. A method of forming a zolmitriptan containing aerosol comprising:

(a) heating a composition containing zolmitriptan coated on a solid support to form a vapor; and

(b) condensing the vapor to form a condensation aerosol comprising particles,

wherein the particles comprise less than 5 percent by weight of zolmitriptan degradation products, and the condensation aerosol has an MMAD of less than 5 microns.

20. The method according to claim 19, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns.

21. The method according to claim 20, wherein the coated composition comprises at least 10 percent by weight of zolmitriptan.

43. The method according to claim 20, wherein the condensing comprises allowing the vapor to cool.

22. A method of forming a sumatriptan containing aerosol comprising:

(a) heating a composition containing sumatriptan coated on a solid support to form a vapor; and

(b) condensing the vapor to form a condensation aerosol comprising particles,

wherein the particles comprise less than 5 percent by weight of sumatriptan degradation products, and the condensation aerosol has an MMAD of less than 5 microns.

23. The method according to claim 22, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns.

24. The method according to claim 23, wherein the coated composition comprises at least 10 percent by weight of sumatriptan.

44. The method according to claim 23, wherein the condensing comprises allowing the vapor to cool.

25. A method of forming a naratriptan containing aerosol comprising:

(a) heating a composition containing naratriptan coated on a solid support to form a vapor; and

(b) condensing the vapor to form a condensation aerosol comprising particles,

wherein the particles comprise less than 5 percent by weight of naratriptan degradation products, and the condensation aerosol has an MMAD of less than 5 microns.

26. The method according to claim 25, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns.

27. The method according to claim 26, wherein the coated composition comprises at least 10 percent by weight of frovatriptan.

45. The method according to claim 26, wherein the condensing comprises allowing the vapor to cool.

28. A method of forming a frovatriptan containing aerosol comprising:

(a) heating a composition containing frovatriptan coated on a solid support to form a vapor; and

(b) condensing the vapor to form a condensation aerosol comprising particles,

wherein the particles comprise less than 5 percent by weight of frovatriptan degradation products, and the condensation aerosol has an MMAD of less than 5 microns.

29. The method according to claim 28, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns.

30. The method according to claim 29, wherein the coated composition comprises at least 10 percent by weight of naratriptan.

46. The method according to claim 29, wherein the condensing comprises allowing the vapor to cool.

31. A method of forming a drug containing aerosol comprising:

(a) heating a composition containing the drug and a pharmaceutically acceptable excipient coated on a solid support to form a vapor; and

(b) condensing the vapor to form a condensation aerosol comprising particles,

wherein the drug is selected from the group consisting of rizatriptan, zolmitriptan, sumatriptan, frovatriptan, and naratriptan, and

wherein the particles comprise at least 10 percent by weight of the drug and less than 5 percent by weight of the drug degradation products, and the condensation aerosol has an MMAD of less than 5 microns.

32. The method according to claim 31, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns.

33. The method according to claim 32, wherein the coated composition comprises at least 10 percent by weight of the drug.

47. The method according to claim 32, wherein the condensing comprises allowing the vapor to cool.

34. A method of forming a drug containing aerosol comprising:

(a) heating a composition containing a salt form of the drug coated on a solid support to form a vapor; and

(b) condensing the vapor to form a condensation aerosol comprising particles,

wherein the drug is selected from the group consisting of rizatriptan, zolmitriptan, sumatriptan, frovatriptan, and naratriptan, and

wherein the particles comprise at least 10 percent by weight of the drug and less than 5 percent by weight of the drug degradation products, and the condensation aerosol has an MMAD of less than 5 microns.

35. The method according to claim 34, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns.

36. The method according to claim 35, wherein the coated composition comprises at least 10 percent by weight of the salt form of the drug.

48. The method according to claim 35, wherein the condensing comprises allowing the vapor to cool.

49. A method of forming a drug containing aerosol comprising:

(a) heating a composition containing the drug coated on a solid support to form a vapor, and

(b) condensing the vapor to form a condensation aerosol comprising particles,

wherein the drug is selected from the group consisting of rizatriptan, zolmitriptan, sumatriptan, frovatriptan, and naratriptan,

wherein the condensation aerosol is formed at a rate greater than 0.5 mg/second, and

wherein the particles comprise at least 10 percent by weight of the drug and less than 5 percent by weight of the drug degradation products, and the condensation aerosol has an MMAD of less than 5 microns.

50. The method according to claim 49, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns.

51. The method according to claim 50, wherein the condensation aerosol is formed at a rate greater than 0.75 mg/second.

52. The method according to claim 51, wherein the condensation aerosol is formed at a rate greater than 1 mg/second.

53. The method according to claim 52, wherein the condensation aerosol is formed at a rate greater than 2 mg/second.

54. The method according to claim 50, wherein the condensing comprises allowing the vapor to cool.