Delivery of opioids through an inhalation route
View Patent ↗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.
1. A condensation aerosol for delivery of a drug selected from the group consisting of naltrexone, buprenorphine, naloxone, butorphanol, hydromorphone, oxycodone, methadone, remifentanil, sufentanil, nalbuphine and fentanyl
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 naltrexone, buprenorphine, naloxone, butorphanol, hydromorphone, oxycodone, methadone, remifentanil, sufentanil, nalbuphine and fentanyl 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 0.2 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 claim 1 , wherein the condensation aerosol is characterized by an MMAD of 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 naltrexone.
14. The condensation aerosol according to claim 1 , wherein the drug is buprenorphine.
15. The condensation aerosol according to claim 1 , wherein the drug is naloxone.
16. The condensation aerosol according to claim 1 , wherein the drug is butorphanol.
17. The condensation aerosol according to claim 1 , wherein the drug is hydromorphone.
18. The condensation aerosol according to claim 1 , wherein the drug is oxycodone.
19. The condensation aerosol according to claim 1 , wherein the drug is methadone.
20. The condensation aerosol according to claim 1 , wherein the drug is remifentanil.
21. The condensation aerosol according to claim 1 , wherein the drug is sufentanil.
22. The condensation aerosol according to claim 1 , wherein the drug is nalbuphine.
23. The condensation aerosol according to claim 1 , wherein the drug is fentanyl.
24. The method according to claim 4 , wherein the condensation aerosol is characterized by an MMAD of 0.2 to 5 microns.
25. The method according to claim 4 , wherein the condensation aerosol is characterized by an MMAD of less than 3 microns.
26. The method according to claim 4 , wherein the condensation aerosol is characterized by an MMAD of 0.2 to 3 microns.
27. The method according to claim 4 , wherein the condensation aerosol is characterized by less than 5% drug degradation products by weight.
28. The method according to claim 27 , wherein the condensation aerosol is characterized by less than 2.5% drug degradation products by weight.
29. The method according to claim 4 , wherein the solid support is a metal foil.
30. The method according to claim 4 , wherein the drug is naltrexone.
31. The method according to claim 4 , wherein the drug is buprenorphine.
32. The method according to claim 4 , wherein the drug is naloxone.
33. The method according to claim 4 , wherein the drug is butorphanol.
34. The method according to claim 4 , wherein the drug is hydromorphone.
35. The method according to claim 4 , wherein the drug is oxycodone.
36. The method according to claim 4 , wherein the drug is methadone.
37. The method according to claim 4 , wherein the drug is remifentanil.
38. The method according to claim 4 , wherein the drug is sufentanil.
39. The method according to claim 4 , wherein the drug is nalbuphine.
40. The method according to claim 4 , wherein the drug is fentanyl.
41. A condensation aerosol for delivery of naltrexone, wherein the condensation aerosol is formed by heating a thin layer containing naltrexone, on a solid support, to produce a vapor of naltrexone, and condensing the vapor to form a condensation aerosol characterized by less than 5% naltrexone degradation products by weight, and an MMAD of 0.2 to 3 microns.
42. A condensation aerosol for delivery of buprenorphine, wherein the condensation aerosol is formed by heating a thin layer containing buprenorphine, on a solid support, to produce a vapor of buprenorphine, and condensing the vapor to form a condensation aerosol characterized by less than 5% buprenorphine degradation products by weight, and an MMAD of 0.2 to 3 microns.
43. A condensation aerosol for delivery of naloxone, wherein the condensation aerosol is formed by heating a thin layer containing naloxone, on a solid support, to produce a vapor of naloxone, and condensing the vapor to form a condensation aerosol characterized by less than 5% naloxone degradation products by weight, and an MMAD of 0.2 to 3 microns.
44. A condensation aerosol for delivery of butorphanol, wherein the condensation aerosol is formed by heating a thin layer containing butorphanol, on a solid support, to produce a vapor of butorphanol, and condensing the vapor to form a condensation aerosol characterized by less than 5% butorphanol degradation products by weight, and an MMAD of 0.2 to 3 microns.
45. A condensation aerosol for delivery of hydromorphone, wherein the condensation aerosol is formed by heating a thin layer containing hydromorphone, on a solid support, to produce a vapor of hydromorphone, and condensing the vapor to form a condensation aerosol characterized by less than 5% hydromorphone degradation products by weight, and an MMAD of 0.2 to 3 microns.
46. A condensation aerosol for delivery of oxycodone, wherein the condensation aerosol is formed by heating a thin layer containing oxycodone, on a solid support, to produce a vapor of oxycodone, and condensing the vapor to form a condensation aerosol characterized by less than 5% oxycodone degradation products by weight, and an MMAD of 0.2 to 3 microns.
47. A condensation aerosol for delivery of methadone, wherein the condensation aerosol is formed by heating a thin layer containing methadone, on a solid support, to produce a vapor of methadone, and condensing the vapor to form a condensation aerosol characterized by less than 5% methadone degradation products by weight, and an MMAD of 0.2 to 3 microns.
48. A condensation aerosol for delivery of remifentanil, wherein the condensation aerosol is formed by heating a thin layer containing remifentanil, on a solid support, to produce a vapor of remifentanil, and condensing the vapor to form a condensation aerosol characterized by less than 5% remifentanil degradation products by weight, and an MMAD of 0.2 to 3 microns.
49. A condensation aerosol for delivery of sufentanil, wherein the condensation aerosol is formed by heating a thin layer containing sufentanil, on a solid support, to produce a vapor of sufentanil, and condensing the vapor to form a condensation aerosol characterized by less than 5% sufentanil degradation products by weight, and an MMAD of 0.2 to 3 microns.
50. A condensation aerosol for delivery of nalbuphine, wherein the condensation aerosol is formed by heating a thin layer containing nalbuphine, on a solid support, to produce a vapor of nalbuphine, and condensing the vapor to form a condensation aerosol characterized by less than 5% nalbuphine degradation products by weight, and an MMAD of 0.2 to 3 microns.
51. A condensation aerosol for delivery of fentanyl, wherein the condensation aerosol is formed by heating a thin layer containing fentanyl, on a solid support, to produce a vapor of fentanyl, and condensing the vapor to form a condensation aerosol characterized by less than 5% fentanyl degradation products by weight, and an MMAD of 0.2 to 3 microns.
52. A method of producing naltrexone in an aerosol form comprising:
a. heating a thin layer containing naltrexone, on a solid support, to produce a vapor of naltrexone, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% naltrexone degradation products by weight, and an MMAD of 0.2 to 3 microns.
53. A method of producing buprenorphine in an aerosol form comprising:
a. heating a thin layer containing buprenorphine, on a solid support, to produce a vapor of buprenorphine, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% buprenorphine degradation products by weight, and an MMAD of 0.2 to 3 microns.
54. A method of producing naloxone in an aerosol form comprising:
a. heating a thin layer containing naloxone, on a solid support, to produce a vapor of naloxone, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% naloxone degradation products by weight, and an MMAD of 0.2 to 3 microns.
55. A method of producing butorphanol in an aerosol form comprising:
a. heating a thin layer containing butorphanol, on a solid support, to produce a vapor of butorphanol, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% butorphanol degradation products by weight, and an MMAD of 0.2 to 3 microns.
56. A method of producing hydromorphone in an aerosol form comprising:
a. heating a thin layer containing hydromorphone, on a solid support, to produce a vapor of hydromorphone, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% hydromorphone degradation products by weight, and an MMAD of 0.2 to 3 microns.
57. A method of producing oxycodone in an aerosol form comprising:
a. heating a thin layer containing oxycodone, on a solid support, to produce a vapor of oxycodone, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% oxycodone degradation products by weight, and an MMAD of 0.2 to 3 microns.
58. A method of producing methadone in an aerosol form comprising:
a. heating a thin layer containing methadone, on a solid support, to produce a vapor of methadone, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% methadone degradation products by weight, and an MMAD of 0.2 to 3 microns.
59. A method of producing remifentanil in an aerosol form comprising:
a. heating a thin layer containing remifentanil, on a solid support, to produce a vapor of remifentanil, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% remifentanil degradation products by weight, and an MMAD of 0.2 to 3 microns.
60. A method of producing sufentanil in an aerosol form comprising:
a. heating a thin layer containing sufentanil, on a solid support, to produce a vapor of sufentanil, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% sufentanil degradation products by weight, and an MMAD of 0.2 to 3 microns.
61. A method of producing nalbuphine in an aerosol form comprising:
a. heating a thin layer containing nalbuphine, on a solid support, to produce a vapor of nalbuphine, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% nalbuphine degradation products by weight, and an MMAD of 0.2 to 3 microns.
62. A method of producing fentanyl in an aerosol form comprising:
a. heating a thin layer containing fentanyl, on a solid support, to produce a vapor of fentanyl, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% fentanyl degradation products by weight, and an MMAD of 0.2 to 3 microns.