Details for Patent: 7,510,702

Title:	Delivery of nonsteroidal antiinflammatory drugs through an inhalation route
Abstract:	The present invention relates to the delivery of nonsteroidal antiinflammatory drugs (NSAIDs) through an inhalation route. Specifically, it relates to aerosols containing NSAIDs that are used in inhalation therapy. In a method aspect of the present invention, an NSAID is delivered to a patient through an inhalation route. The method comprises: a) heating a coating of an NSAID, on a solid support, to form a vapor; and, b) passing air through the heated vapor to produce aerosol particle having less than 5% NSAID degradation products. In a kit aspect of the present invention, a kit for delivering an NSAID through an inhalation route is provided which comprises: a) a coating of an NSAID composition and b) a device for dispensing said coating 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:	Aug 07, 2006
Application Number:	11/501,246
Claims:	1. A condensation aerosol for delivery of indomethacin formed by heating a composition containing indomethacin 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 indomethacin and less than 5 percent by weight of indomethacin 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. 4. A condensation aerosol for delivery of ketoprofen formed by heating a composition containing ketoprofen 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 ketoprofen and less than 5 percent by weight of ketoprofen 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 between 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. 7. A condensation aerosol for delivery of celecoxib formed by heating a composition containing celecoxib 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 celecoxib and less than 5 percent by weight of celecoxib 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. 10. A condensation aerosol for delivery of rofecoxib formed by heating a composition containing rofecoxib 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 rofecoxib and less than 5 percent by weight of rofecoxib 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. 13. A condensation aerosol for delivery of meclofenamic acid formed by heating a composition containing meclofenamic acid 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 meclofenamic acid and less than 5 percent by weight of meclofenamic acid 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. 16. A condensation aerosol for delivery of fenoprofen formed by heating a composition containing fenoprofen 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 fenoprofen and less than 5 percent by weight of fenoprofen 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 16 or claim 17, wherein the geometric standard deviation around the MMAD is less than 3.0. 19. A condensation aerosol for delivery of diflunisal formed by heating a composition containing diflunisal 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 diflunisal and less than 5 percent by weight of diflunisal 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 19 or claim 20, wherein the geometric standard deviation around the MMAD is less than 3.0. 22. A condensation aerosol for delivery of naproxen formed by heating a composition containing naproxen 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 naproxen and less than 5 percent by weight of naproxen 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 22 or claim 23, wherein the geometric standard deviation around the MMAD is less than 3.0. 25. A condensation aerosol for delivery of ibuprofen formed by heating a composition containing ibuprofen 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 ibuprofen and less than 5 percent by weight of ibuprofen 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 25 or claim 26, wherein the geometric standard deviation around the MMAD is less than 3.0. 28. A condensation aerosol for delivery of flurbiprofen formed by heating a composition containing flurbiprofen 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 flurbiprofen and less than 5 percent by weight of flurbiprofen 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 28 or claim 29, wherein the geometric standard deviation around the MMAD is less than 3.0. 31. A condensation aerosol for delivery of nabumetone formed by heating a composition containing nabumetone 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 nabumetone and less than 5 percent by weight of nabumetone 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 to 0.2 to 3 microns. 33. The condensation aerosol according to claim 31 or claim 32, wherein the geometric standard deviation around the MMAD is less than 3.0. 34. A method of forming an indomethacin containing aerosol comprising: (a) heating a composition containing indomethacin 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 indomethacin 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 indomethacin. 37. A method of forming a ketoprofen containing aerosol comprising: (a) heating acomposition containing ketoprofen 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 ketoprofen 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 ketoprofen. 40. A method of forming a celecoxib containing aerosol comprising: (a) heating a composition containing celecoxib 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 os celecoxib 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 celecoxib. 43. A method of forming a rofecoxib containing aerosol comprising: (a) heating a composition containing rofecoxib 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 rofecoxib 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 rofecoxib. 46. A method of forming a meclofenamic acid containing aerosol comprising: (a) heating a composition containing meclofenamic acid 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 meclofenamic acid degradation Products, 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 meclofenamic acid. 49. A method of forming a fenoprofen containing aerosol comprising: (a) heating a compostion containing fenoprofen 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 fenoprofen 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 fenoprofen. 52. A method of forming a diflunisal containing aerosol comprising: (a) heating a composition containing diflunisal 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 diflunisal degradation products, 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 diflunisal. 55. A method of forming a naproxen containing aerosol comprising: (a) heating a composition containing naproxen 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 naproxen of 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 naproxen. 58. A method of forming an ibuprofen containing aerosol comprising: (a) heating a composition containing ibuprofen 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 ibuprofen 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 between 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 ibuprofen. 61. A method of forming a flurbiprofen containing aerosol comprising: (a) heating a composition containing flurbiprofen 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 flurbiprofen 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 flurbiprofen. 64. A method of forming a nabumetone containing aerosol comprising: (a) heating a composition containing nabumetone coated on a solid support to form a vapor; and (b) condensing the vapor to produce a condensation aerosol comprising particles, wherein the particles comprise less than 5 percent by weight of nabumetone 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 nabumetone. 67. A method of forming a tolfenamic acid containing aerosol comprising: (a) heating a composition containing tolfenamic acid 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 tolfenamic acid degradation products, and the condensation aerosol has an MMAD of less than 5 microns. 68. The method according to claim 67, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns. 69. The method according to claim 68, wherein the coated composition comprises at least 10 percent by weight of tolfenamic acid. 70. 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 indomethacin, ketoprofen, celecoxib, rofecoxib, meclofenamic acid, fenoprofen, diflunisal, tolfenamic acid, naproxen, ibuprofen, flurbiprofen, and nabumetone, 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. 71. The method according to claim 70, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns. 72. The method according to claim 71, wherein the coated composition comprises at least 10 percent by weight of the drug. 73. 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 indomethacin, ketoprofen, celecoxib, rofecoxib, meclofenamic acid, fenoprofen, diflunisal, tolfenamic acid, naproxen, ibuprofen, flurbiprofen, and nabumetone, 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. 74. The method according to claim 73, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns. 75. The method according to claim 74, wherein the coated composition comprises at least 10 percent by weight of the salt form of the drug. 76. A condensation aerosol for delivery of tolfenamic acid formed by heating a composition containing tolfenamic acid 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 tolfenamic acid and less than 5 percent by weight of tolfenamic acid degradation products, and the condensation aerosol has an MMAD of less than 5 microns. 77. The condensation aerosol according to claim 76, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns. 78. The condensation aerosol according to claim 76 or claim 77, wherein the geometric standard deviation around the MMAD is less than 3.0. 79. The condensation aerosol according to claim 2, wherein the condensing comprises allowing the vapor to cool. 80. The condensation aerosol according to claim 5, wherein the condensing comprises allowing the vapor to cool. 81. The condensation aerosol according to claim 8, wherein the condensing comprises allowing the vapor to cool. 82. The condensation aerosol according to claim 11, wherein the condensing comprises allowing the vapor to cool. 83. The condensation aerosol according to claim 14, wherein the condensing comprises allowing the vapor to cool. 84. The condensation aerosol according to claim 17, wherein the condensing comprises allowing the vapor to cool. 85. The condensation aerosol according to claim 20, wherein the condensing comprises allowing the vapor to cool. 86. The condensation aerosol according to claim 23, wherein the condensing comprises allowing the vapor to cool. 87. The condensation aerosol according to claim 26, wherein the condensing comprises allowing the vapor to cool. 88. The condensation aerosol according to claim 29, wherein the condensing comprises allowing the vapor to cool. 89. The condensation aerosol according to claim 32, wherein the condensing comprises allowing the vapor to cool. 90. The condensation aerosol according to claim 77, wherein the condensing comprises allowing the vapor to cool. 91. The method according to claim 35, wherein the condensing comprises allowing the vapor to cool. 92. The method according to claim 38, wherein the condensing comprises allowing the vapor to cool. 93. The method according to claim 41, wherein the condensing comprises allowing the vapor to cool. 94. The method according to claim 44, wherein the condensing comprises allowing the vapor to cool. 95. The method according to claim 47, wherein the condensing comprises allowing the vapor to cool. 96. The method according to claim 50, wherein the condensing comprises allowing the vapor to cool. 97. The method according to claim 53, wherein the condensing comprises allowing the vapor to cool. 98. The method according to claim 56, wherein the condensing comprises allowing the vapor to cool. 99. The method according to claim 59, wherein the condensing comprises allowing the vapor to cool. 100. The method according to claim 62, wherein the condensing comprises allowing the vapor to cool. 101. The method according to claim 65, wherein the condensing comprises allowing the vapor to cool. 102. The method according to claim 68, wherein the condensing comprises allowing the vapor to cool. 103. The method according to claim 71, wherein the condensing comprises allowing the vapor to cool. 104. The method according to claim 74, wherein the condensing comprises allowing the vapor to cool. 105. 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 indomethacin, ketoprofen, celecoxib, rofecoxib, meclofenamic acid, fenoprofen, diflunisal, tolfenamic acid, naproxen, ibuprofen, flurbiprofen, and nabumetone, 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. 106. The method according to claim 105, wherein the condensation aerosol has an MMAD of 0.2 to 3 microns. 107. The method according to claim 106, wherein the condensation aerosol is formed at a rate greater than 0.75 mg/second. 108. The method according to claim 107, wherein the condensation aerosol is formed at a rate greater than 1 mg/second. 109. The method according to claim 108, wherein the condensation aerosol is formed at a rate greater than 2 mg/second. 110. The method according to claim 105, wherein the condensing comprises allowing the vapor to cool.