Details for Patent: 7,078,018

Title:	Delivery of opioids through an inhalation route
Abstract:	The present invention relates to the delivery of opioids through an inhalation route. Specifically, it relates to aerosols containing opioids that are used in inhalation therapy. In a method aspect of the present invention, an opioid is delivered to a patient through an inhalation route. The method comprises: a) heating a composition, wherein the composition comprises an opioid, to form a vapor; and, b) allowing the vapor to cool, thereby forming a condensation aerosol comprising particles with less than 5% opioid degradation products. In a kit aspect of the present invention, a kit for delivering an opioid through an inhalation route is provided which comprises: a) a thin coating of an opioid composition and b) a device for dispensing said thin coating as a condensation aerosol.
Inventor(s):	Rabinowitz; Joshua D. (Mountain View, CA), Zaffaroni; Alejandro C. (Atherton, CA)
Assignee:	Alexza Pharmaceuticals, Inc. (Palo Alto, CA)
Filing Date:	Dec 30, 2003
Application Number:	10/749,539
Claims:	1. A method of treating pain or alcohol abuse in a patient, or providing opioid reversal therapy or opioid maintenance therapy to a patient comprising administering a therapeutic amount of a drug condensation aerosol to the patient by inhalation, wherein the drug is selected from the group consisting of fentanyl, naltrexone, buprenorphine, naloxone, butorphanol, hydromorphone, oxycodone, methadone, remifentanil and sufentanil, and wherein the condensation aerosol is formed by heating a thin layer containing the drug, on a solid support, to produce a vapor of the drug, and condensing the vapor to form a condensation aerosol characterized by less than 10% drug degradation products by weight, and an MMAD of less than 5 microns. 2. The method according to claim 1, wherein the condensation aerosol is characterized by an MMAD of less than 3 microns. 3. The method according to claim 1, wherein peak plasma drug concentration is reached in less than 0.1 hours. 4. The method according to claim 1, wherein the condensation aerosol is formed at a rate greater than 0.5 mg/second. 5. The method according to claim 1, wherein at least 50% by weight of the condensation aerosol is amorphous in form. 6. The method according to claim 1, wherein the therapeutic amount of a drug condensation aerosol comprises between 0.01 mg and 0.8 mg of fentanyl delivered in a single inspiration. 7. The method according to claim 1, wherein the therapeutic amount of a drug condensation aerosol comprises between 15 mg and 35 mg of naltrexone delivered in a single inspiration. 8. The method according to claim 1, wherein the therapeutic amount of a drug condensation aerosol comprises between 0.1 mg and 1 mg of buprenorphine delivered in a single inspiration. 9. The method according to claim 1, wherein the therapeutic amount of a drug condensation aerosol comprises between 0.05 mg and 3.5 mg of naloxone delivered in a single inspiration. 10. The method according to claim 1, wherein the therapeutic amount of a drug condensation aerosol comprises between 0.1 mg and 3 mg of butorphanol delivered in a single inspiration. 11. The method according to claim 1, wherein the therapeutic amount of a drug condensation aerosol comprises between 0.1 mg and 10 mg of hydromorphone delivered in a single inspiration. 12. The method according to claim 1, wherein the therapeutic amount of a drug condensation aerosol comprises between 0.5 mg and 10 mg of oxycodone delivered in a single inspiration. 13. The method according to claim 1, wherein the therapeutic amount of a drug condensation aerosol comprises between 0.25 mg and 20 mg of methadone delivered in a single inspiration. 14. A method of administering a drug condensation aerosol to a patient comprising administering the drug condensation aerosol to the patient by inhalation, wherein the drug is selected from the group consisting of fentanyl, naltrexone, buprenorphine, naloxone, butorphanol, hydromorphone, oxycodone, methadone, remifentanil and sufentanil, and wherein the drug condensation aerosol is formed by heating a thin layer containing the drug, on a solid support, to produce a vapor of the drug, and condensing the vapor to form a condensation aerosol characterized by less than 10% drug degradation products by weight, and an MMAD of less than 5 microns. 15. A kit for delivering a drug condensation aerosol comprising: a. a thin layer containing the drug, on a solid support, wherein the drug is selected from the group consisting of fentanyl, naltrexone, buprenorphine, naloxone, butorphanol, hydromorphone, oxycodone, methadone, remifentanil and sufentanil, and b. a device for providing the condensation aerosol, wherein the condensation aerosol is formed by heating the thin layer to produce a vapor of the drug, and condensing the vapor to form a condensation aerosol characterized by less than 10% drug degradation products by weight, and an MMAD of less than 5 microns. 16. The kit according to claim 15, wherein the device comprises: a. a flow through enclosure containing the solid support, b. a power source that can be activated to heat the solid support, and c. at least one portal through which air can be drawn by inhalation, wherein activation of the power source is effective to produce a vapor of the drug, and drawing air through the enclosure is effective to condense the vapor to form the condensation aerosol. 17. The kit according to claim 16, wherein the heat for heating the solid support is generated by an exothermic chemical reaction. 18. The kit according to claim 17, wherein the exothermic chemical reaction is oxidation of combustible materials. 19. The kit according to claim 16, wherein the heat for heating the solid support is generated by passage of current through an electrical resistance element. 20. The kit according to claim 16, wherein the solid support has a surface area dimensioned to accommodate a therapeutic dose of the drug. 21. The kit according to claim 15, wherein peak plasma drug concentration is reached in less than 0.1 hours. 22. The kit according to claim 15, further including instructions for use. 23. The method according to claim 1, wherein the condensation aerosol is characterized by an MMAD of 0.1 to 5 microns. 24. The method according to claim 1, wherein the condensation aerosol is characterized by an MMAD of about 0.2 to about 3 microns. 25. The method according to claim 14, wherein the drug is fentanyl. 26. The method according to claim 14, wherein the drug is naltrexone. 27. The method according to claim 14, wherein the drug is buprenorphine. 28. The method according to claim 14, wherein the drug is naloxone. 29. The method according to claim 14, wherein the drug is butorphanol. 30. The method according to claim 14, wherein the drug is hydromorphone. 31. The method according to claim 14, wherein the drug is oxycodone. 32. The method according to claim 14, wherein the drug is methadone. 33. The method according to claim 14, wherein the drug is remifentanil. 34. The method according to claim 14, wherein the drug is sufentanil. 35. The kit according to claim 15, wherein the condensation aerosol is characterized by an MMAD of less than 3 microns. 36. The kit according to claim 15, wherein the condensation aerosol is characterized by an MMAD of 0.1 to 5 microns. 37. The kit according to claim 15, wherein the condensation aerosol is characterized by an MMAD of about 0.2 to about 3 microns. 38. The kit according to claim 15, wherein the drug is fentanyl. 39. The kit according to claim 15, wherein the drug is naltrexone. 40. The kit according to claim 15, wherein the drug is buprenorphine. 41. The kit according to claim 15, wherein the drug is naloxone. 42. The kit according to claim 15, wherein the drug is butorphanol. 43. The kit according to claim 15, wherein the drug is hydromorphone. 44. The kit according to claim 15, wherein the drug is oxycodone. 45. The kit according to claim 15, wherein the drug is methadone. 46. The kit according to claim 15, wherein the drug is remifentanil. 47. The kit according to claim 15, wherein the drug is sufentanil. 48. The kit according to claim 16, wherein the solid support has a surface to mass ratio of greater than 1 cm.sup.2 per gram. 49. The kit according to claim 16, wherein the solid support has a surface to volume ratio of greater than 100 per meter. 50. The kit according to claim 16, wherein the solid support is a metal foil. 51. The kit according to claim 50, wherein the metal foil has a thickness of less than 0.25 mm.