Delivery of nonsteroidal antiinflammatory drugs through an inhalation route
View Patent ↗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.
1. A condensation aerosol for delivery of a drug selected from the group consisting of indomethacin, ketoprofen, celcoxib, rofecoxib, meclofenamic acid, fenoprofen, diflunisal, tolfenamic acid, naproxen, ibuprofen, flurbiprofen and nabumetone, 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 condensation aerosol according to claim 1 , wherein the condensation aerosol is formed at a rate greater than 10 9 particles per second.
3. The condensation aerosol according to claim 2 , wherein the condensation aerosol is formed at a rate greater than 10 10 particles per second.
4. A method of producing a drug selected from the group consisting of indomethacin, ketoprofen, celcoxib, rofecoxib, meclofenamic acid, fenoprofen, diflunisal, tolfenamic acid, naproxen, ibuprofen, flurbiprofen and nabumetone in an aerosol form comprising:
a. heating a thin layer containing the drug, on a solid support, to produce a vapor of the drug, and
b. providing an air flow through 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.
5. The method according to claim 4 , wherein the condensation aerosol is formed at a rate greater than 10 9 particles per second.
6. The method according to claim 5 , wherein the condensation aerosol is formed at a rate greater than 10 10 particles per second.
7. The condensation aerosol according to claim 1 , wherein the condensation aerosol is characterized by an MMAD of 0.1 to 5 microns.
8. The condensation aerosol according to claim 1 , wherein the condensation aerosol is characterized by an MMAD of less than 3 microns.
9. The condensation aerosol according to claim 1 , wherein the condensation aerosol is characterized by an MMAD of about 0.2 to 3 microns.
10. The condensation aerosol according to claim 1 , wherein the condensation aerosol is characterized by less than 5% drug degradation products by weight.
11. The condensation aerosol according to claim 10 , wherein the condensation aerosol is characterized by less than 2.5% drug degradation products by weight.
12. The condensation aerosol according to claim 1 , wherein the solid support is a metal foil.
13. The condensation aerosol according to claim 1 , wherein the drug is indomethacin.
14. The condensation aerosol according to claim 1 , wherein the drug is ketoprofen.
15. The condensation aerosol according to claim 1 , wherein the drug is celcoxib.
16. The condensation aerosol according to claim 1 , wherein the drug is rofecoxib.
17. The condensation aerosol according to claim 1 , wherein the drug is meclofenamic acid.
18. The condensation aerosol according to claim 1 , wherein the drug is fenoprofen.
19. The condensation aerosol according to claim 1 , wherein the drug is diflunisal.
20. The condensation aerosol according to claim 1 , wherein the drug is tolfenamic acid.
21. The condensation aerosol according to claim 1 , wherein the drug is naproxen.
22. The condensation aerosol according to claim 1 , wherein the drug is ibuprofen.
23. The condensation aerosol according to claim 1 , wherein the drug is flurbiprofen.
24. The condensation aerosol according to claim 1 , wherein the drug is nabumetone.
25. The method according to claim 4 , wherein the condensation aerosol is characterized by an MMAD of 0.1 to 5 microns.
26. The method according to claim 4 , wherein the condensation aerosol is characterized by an MMAD of less than 3 microns.
27. The method according to claim 4 , wherein the condensation aerosol is characterized by an MMAD of about 0.2 to 3 microns.
28. The method according to claim 4 , wherein the condensation aerosol is characterized by less than 5% drug degradation products by weight.
29. The method according to claim 28 , wherein the condensation aerosol is characterized by less than 2.5% drug degradation products by weight.
30. The method according to claim 4 , wherein the solid support is a metal foil.
31. The method according to claim 4 , wherein the drug is indomethacin.
32. The method according to claim 4 , wherein the drug is ketoprofen.
33. The method according to claim 4 , wherein the drug is celcoxib.
34. The method according to claim 4 , wherein the drug is rofecoxib.
35. The method according to claim 4 , wherein the drug is meclofenamic acid.
36. The method according to claim 4 , wherein the drug is fenoprofen.
37. The method according to claim 4 , wherein the drug is diflunisal.
38. The method according to claim 4 , wherein the drug is tolfenamic acid.
39. The method according to claim 4 , wherein the drug is naproxen.
40. The method according to claim 4 , wherein the drug is ibuprofen.
41. The method according to claim 4 , wherein the drug is flurbiprofen.
42. The method according to claim 4 , wherein the drug is nabumetone.
43. A condensation aerosol for delivery of indomethacin, wherein the condensation aerosol is formed by heating a thin layer containing indomethacin, on a solid support, to produce a vapor of indomethacin, and condensing the vapor to form a condensation aerosol characterized by less than 5% indomethacin degradation products by weight, and an MMAD of about 0.2 to 3 microns.
44. A condensation aerosol for delivery of ketoprofen, wherein the condensation aerosol is formed by heating a thin layer containing ketoprofen, on a solid support, to produce a vapor of ketoprofen, and condensing the vapor to form a condensation aerosol characterized by less than 5% ketoprofen degradation products by weight, and an MMAD of about 0.2 to 3 microns.
45. A condensation aerosol for delivery of celcoxib, wherein the condensation aerosol is formed by heating a thin layer containing celcoxib, on a solid support, to produce a vapor of celcoxib, and condensing the vapor to form a condensation aerosol characterized by less than 5% celcoxib degradation products by weight, and an MMAD of about 0.2 to 3 microns.
46. A condensation aerosol for delivery of rofecoxib, wherein the condensation aerosol is formed by heating a thin layer containing rofecoxib, on a solid support, to produce a vapor of rofecoxib, and condensing the vapor to form a condensation aerosol characterized by less than 5% rofecoxib degradation products by weight, and an MMAD of about 0.2 to 3 microns.
47. A condensation aerosol for delivery of meclofenamic acid, wherein the condensation aerosol is formed by heating a thin layer containing meclofenamic acid, on a solid support, to produce a vapor of meclofenamic acid, and condensing the vapor to form a condensation aerosol characterized by less than 5% meclofenamic acid degradation products by weight, and an MMAD of about 0.2 to 3 microns.
48. A condensation aerosol for delivery of fenoprofen, wherein the condensation aerosol is formed by heating a thin layer containing fenoprofen, on a solid support, to produce a vapor of fenoprofen, and condensing the vapor to form a condensation aerosol characterized by less than 5% fenoprofen degradation products by weight, and an MMAD of 0.2 to 3 microns.
49. A condensation aerosol for delivery of diflunisal, wherein the condensation aerosol is formed by heating a thin layer containing diflunisal, on a solid support, to produce a vapor of diflunisal, and condensing the vapor to form a condensation aerosol characterized by less than 5% diflunisal degradation products by weight, and an MMAD of about 0.2 to 3 microns.
50. A condensation aerosol for delivery of tolfenamic acid, wherein the condensation aerosol is formed by heating a thin layer containing tolfenamic acid, on a solid support, to produce a vapor of tolfenamic acid, and condensing the vapor to form a condensation aerosol characterized by less than 5% tolfenamic acid degradation products by weight, and an MMAD of about 0.2 to 3 microns.
51. A condensation aerosol for delivery of naproxen, wherein the condensation aerosol is formed by heating a thin layer containing naproxen, on a solid support, to produce a vapor of naproxen, and condensing the vapor to form a condensation aerosol characterized by less than 5% naproxen degradation products by weight, and an MMAD of about 0.2 to 3 microns.
52. A condensation aerosol for delivery of ibuprofen, wherein the condensation aerosol is formed by heating a thin layer containing ibuprofen, on a solid support, to produce a vapor of ibuprofen, and condensing the vapor to form a condensation aerosol characterized by less than 5% ibuprofen degradation products by weight, and an MMAD of about 0.2 to 3 microns.
53. A condensation aerosol for delivery of flurbiprofen, wherein the condensation aerosol is formed by heating a thin layer containing flurbiprofen, on a solid support, to produce a vapor of flurbiprofen, and condensing the vapor to form a condensation aerosol characterized by less than 5% flurbiprofen degradation products by weight, and an MMAD of about 0.2 to 3 microns.
54. A condensation aerosol for delivery of nabumetone, wherein the condensation aerosol is formed by heating a thin layer containing nabumetone, on a solid support, to produce a vapor of nabumetone, and condensing the vapor to form a condensation aerosol characterized by less than 5% nabumetone degradation products by weight, and an MMAD of about 0.2 to 3 microns.
55. A method of producing indomethacin in an aerosol form comprising:
a. heating a thin layer containing indomethacin, on a solid support, to produce a vapor of indomethacin, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% indomethacin degradation products by weight, and an MMAD of about 0.2 to 3 microns.
56. A method of producing ketoprofen in an aerosol form comprising:
a. heating a thin layer containing ketoprofen, on a solid support, to produce a vapor of ketoprofen, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% ketoprofen degradation products by weight, and an MMAD of about 0.2 to 3 microns.
57. A method of producing celcoxib in an aerosol form comprising:
a. heating a thin layer containing celcoxib, on a solid support, to produce a vapor of celcoxib, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% celcoxib degradation products by weight, and an MMAD of about 0.2 to 3 microns.
58. A method of producing rofecoxib in an aerosol form comprising:
a. heating a thin layer containing rofecoxib, on a solid support, to produce a vapor of rofecoxib, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% rofecoxib degradation products by weight, and an MMAD of about 0.2 to 3 microns.
59. A method of producing meclofenamic acid in an aerosol form comprising:
a. heating a thin layer containing meclofenamic acid, on a solid support, to produce a vapor of meclofenamic acid, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% meclofenamic acid degradation products by weight, and an MMAD of about 0.2 to 3 microns.
60. A method of producing fenoprofen in an aerosol form comprising:
a. heating a thin layer containing fenoprofen, on a solid support, to produce a vapor of fenoprofen, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% fenoprofen degradation products by weight, and an MMAD of about 0.2 to 3 microns.
61. A method of producing diflunisal in an aerosol form comprising:
a. heating a thin layer containing diflunisal, on a solid support, to produce a vapor of diflunisal, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% diflunisal degradation products by weight, and an MMAD of about 0.2 to 3 microns.
62. A method of producing tolfenamic acid in an aerosol form comprising:
a. heating a thin layer containing tolfenamic acid, on a solid support, to produce a vapor of tolfenamic acid, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% tolfenamic acid degradation products by weight, and an MMAD of about 0.2 to 3 microns.
63. A method of producing naproxen in an aerosol form comprising:
a. heating a thin layer containing naproxen, on a solid support, to produce a vapor of naproxen, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% naproxen degradation products by weight, and an MMAD of about 0.2 to 3 microns.
64. A method of producing ibuprofen in an aerosol form comprising:
a. heating a thin layer containing ibuprofen, on a solid support, to produce a vapor of ibuprofen, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% ibuprofen degradation products by weight, and an MMAD of about 0.2 to 3 microns.
65. A method of producing flurbiprofen in an aerosol form comprising:
a. heating a thin layer containing flurbiprofen, on a solid support, to produce a vapor of flurbiprofen, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% flurbiprofen degradation products by weight, and an MMAD of about 0.2 to 3 microns.
66. A method of producing nabumetone in an aerosol form comprising:
a. heating a thin layer containing nabumetone, on a solid support, to produce a vapor of nabumetone, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% nabumetone degradation products by weight, and an MMAD of about 0.2 to 3 microns.