Details for Patent: 7,468,179

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 thin layer of an opioid, on a solid support, to form a vapor; and, b) passing air through the heated vapor to produce aerosol particles having 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 layer of an opioid and b) a device for dispensing said thin layer as a condensation aerosol.
Inventor(s):	Rabinowitz; Joshua D. (Princeton, NJ), Zaffaroni; Alejandro C. (Atherton, CA)
Assignee:	Alexza Pharmaceuticals, Inc. (Mountain View, CA)
Filing Date:	Jan 09, 2007
Application Number:	11/621,397
Claims:	1. A condensation aerosol for delivery of naltrexone formed by heating a composition containing naltrexone 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 naltrexone and less than 5 percent by weight of naltrexone 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 2, wherein the condensing comprises allowing the vapor to cool. 4. A condensation aerosol for delivery of buprenorphine formed by heating a composition containing buprenorphine 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 buprenorphine and less than 5 percent by weight of buprenorphine 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 5, wherein the condensing comprises allowing the vapor to cool. 7. A condensation aerosol for delivery of naloxone formed by heating a composition containing naloxone 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 naloxone and less than 5 percent by weight of naloxone 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 8, wherein the condensing comprises allowing the vapor to cool. 10. A condensation aerosol for delivery of butorphanol formed by heating a composition containing butorphanol 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 butorphanol and less than 5 percent by weight of butorphanol 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 11, wherein the condensing comprises allowing the vapor to cool. 13. A condensation aerosol for delivery of hydromorphone formed by heating a composition containing hydromorphone 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 hydromorphone and less than 5 percent by weight of hydromorphone 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 14, wherein the condensing comprises allowing the vapor to cool. 16. A condensation aerosol for delivery of oxycodone formed by heating a composition containing oxycodone 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 oxycodone and less than 5 percent by weight of oxycodone degradation products, and the condensation aerosol has an MMAD of less than 5 microns. 17. The condensation aerosol according to claim 16, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns. 18. The condensation aerosol according to claim 17, wherein the condensing comprises allowing the vapor to cool. 19. A condensation aerosol for delivery of methadone formed by heating a composition containing methadone 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 methadone and less than 5 percent by weight of methadone degradation products, and the condensation aerosol has an MMAD of less than 5 microns. 20. The condensation aerosol according to claim 19, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns. 21. The condensation aerosol according to claim 20, wherein the condensing comprises allowing the vapor to cool. 22. A condensation aerosol for delivery of remifentanil formed by heating a composition containing remifentanil 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 remifentanil and less than 5 percent by weight of remifentanil degradation products, and the condensation aerosol has an MMAD of less than 5 microns. 23. The condensation aerosol according to claim 22, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns. 24. The condensation aerosol according to claim 23, wherein the condensing comprises allowing the vapor to cool. 25. A condensation aerosol for delivery of sufentanil formed by heating a composition containing sufentanil 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 sufentanil and less than 5 percent by weight of sufentanil degradation products, and the condensation aerosol has an MMAD of less than 5 microns. 26. The condensation aerosol according to claim 25, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns. 27. The condensation aerosol according to claim 26, wherein the condensing comprises allowing the vapor to cool. 28. A condensation aerosol for delivery of nalbuphine formed by heating a composition containing nalbuphine 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 nalbuphine and less than 5 percent by weight of nalbuphine degradation products, and the condensation aerosol has an MMAD of less than 5 microns. 29. The condensation aerosol according to claim 28, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns. 30. The condensation aerosol according to claim 29, wherein the condensing comprises allowing the vapor to cool. 31. A condensation aerosol for delivery of fentanyl formed by heating a composition containing fentanyl 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 fentanyl and less than 5 percent by weight of fentanyl degradation products, and the condensation aerosol has an MMAD of less than 5 microns. 32. The condensation aerosol according to claim 31, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns. 33. The condensation aerosol according to claim 32, wherein the condensing comprises allowing the vapor to cool. 34. A method of forming a naltrex one containing aerosol comprising: (a) heating a composition containing naltrexone 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 naltrexone 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 naltrexone. 37. A method of forming a buprenorphine containing aerosol comprising: (a) heating a composition containing buprenorphine 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 buprenorphine degradation products, and the condensation aerosol has an MMAD of less than 5 microns. 38. The method according to claim 37, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns. 39. The method according to claim 38, wherein the coated composition comprises at least 10 percent by weight of buprenorphine. 40. A method of forming a naloxone containing aerosol comprising: (a) heating a composition containing naloxone 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 naloxone degradation products, and the condensation aerosol has an MMAD of less than 5 microns. 41. The method according to claim 40, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns. 42. The method according to claim 41, wherein the coated composition comprises at least 10 percent by weight of naloxone. 43. A method of forming a butorphanol containing aerosol comprising: (a) heating a composition containing butorphanol 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 butorphanol degradation products, and the condensation aerosol has an MMAD of less than 5 microns. 44. The method according to claim 43, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns. 45. The method according to claim 44, wherein the coated composition comprises at least 10 percent by weight of butorphanol. 46. A method of forming a hydromorphone containing aerosol comprising: (a) heating a composition containing hydromorphone 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 hydromorphone degradation product% and the condensation aerosol has an MMAD of less than 5 microns. 47. The method according to claim 46, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns. 48. The method according to claim 47, wherein the coated composition comprises at least 10 percent by weight of hydromorphone. 49. A method of forming an oxycodone containing aerosol comprising: (a) heating a composition containing oxycodone 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 oxycodone 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 coated composition comprises at least 10 percent by weight of oxycodone. 52. A method of forming a methadone containing aerosol comprising: (a) heating a composition containing methadone 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 methadone degradation product% and the condensation aerosol has an MMAD of less than 5 microns. 53. The method according to claim 52, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns. 54. The method according to claim 53, wherein the coated composition comprises at least 10 percent by weight of methadone. 55. A method of forming a remifentanil containing aerosol comprising: (a) heating a composition containing remifentanil 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 remifentanil degradation products, and the condensation aerosol has an MMAD of less than 5 microns. 56. The method according to claim 55, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns. 57. The method according to claim 56, wherein the coated composition comprises at least 10 percent by weight of remifentanil. 58. A method of forming a sufentanil containing aerosol comprising: (a) heating a composition containing sufentanil 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 sufentanil degradation products, and the condensation aerosol has an MMAD of less than 5 microns. 59. The method according to claim 58, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns. 60. The method according to claim 59, wherein the coated composition comprises at least 10 percent by weight of sufentanil. 61. A method of forming a fentanyl containing aerosol comprising: (a) heating a composition containing fentanyl 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 fentanyl degradation products, and the condensation aerosol has an MMAD of less than 5 microns. 62. The method according to claim 61, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns. 63. The method according to claim 62, wherein the coated composition comprises at least 10 percent by weight of fentanyl. 64. A method of forming a nalbuphine containing aerosol comprising: (a) heating a composition containing nalbuphine 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 nalbuphine degradation products, and the condensation aerosol has an MMAD of less than 5 microns. 65. The method according to claim 64, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns. 66. The method according to claim 65, wherein the coated composition comprises at least 10 percent by weight of nalbuphine. 67. The method according to claim 35, wherein the condensing comprises allowing the vapor to cool. 68. The method according to claim 38, wherein the condensing comprises allowing the vapor to cool. 69. The method according to claim 41, wherein the condensing comprises allowing the vapor to cool. 70. The method according to claim 44, wherein the condensing comprises allowing the vapor to cool. 71. The method according to claim 47, wherein the condensing comprises allowing the vapor to cool. 72. The method according to claim 50, wherein the condensing comprises allowing the vapor to cool. 73. The method according to claim 53, wherein the condensing comprises allowing the vapor to cool. 74. The method according to claim 56, wherein the condensing comprises allowing the vapor to cool. 75. The method according to claim 59, wherein the condensing comprises allowing the vapor to cool. 76. The method according to claim 62, wherein the condensing comprises allowing the vapor to cool. 77. The method according to claim 65, wherein the condensing comprises allowing the vapor to cool. 78. 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 naltrexone, buprenorphine, nalbuphine, naloxone, butorphanol, hydromorphone, oxycodone, methadone, remifentanil, sufentanil, and fentanyl, 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. 79. The method according to claim 78, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns. 80. The method according to claim 79, wherein the coated composition comprises at least 10 percent by weight of the drug. 81. The method according to claim 79, wherein the condensing comprises allowing the vapor to cool. 82. 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 naltrexone, buprenorphine, nalbuphine, naloxone, butorphanol, hydromorphone, oxycodone, methadone, remifentanil, sufentanil, and fentanyl, 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. 83. The method according to claim 82, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns. 84. The method according to claim 83, wherein the coated composition comprises at least 10 percent by weight of the salt form of the drug. 85. The method according to claim 83, wherein the condensing comprises allowing the vapor to cool. 86. 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 naltrexone, buprenorphine, nalbuphine, naloxone, butorphanol, hydromorphone, oxycodone, methadone, remifentanil, sufentanil, and fentanyl, 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. 87. The method according to claim 86, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns. 88. The method according to claim 87, wherein the condensation aerosol is formed at a rate greater than 0.75 mg/second. 89. The method according to claim 88, wherein the condensation aerosol is formed at a rate greater than 1 mg/second. 90. The method according to claim 89, wherein the condensation aerosol is formed at a rate greater than 2 mg/second. 91. The method according to claim 86, wherein the condensing comprises allowing the vapor to cool.