Delivery of anti-migraine compounds through an inhalation route
View Patent ↗The present invention relates to the delivery of anti-migraine compounds through an inhalation route. Specifically, it relates to aerosols containing lidocaine, verapamil, diltiazem, isometheptene, or lisuride that are used in inhalation therapy. In a method aspect of the present invention, lidocaine, verapamil, diltiazem, isometheptene, or lisuride is administered to a patient through an inhalation route. The method comprises: a) heating a thin layer of lidocaine, verapamil, diltiazem, isometheptene, or lisuride, on a solid support to form a vapor; and, b) passing air through the heated vapor to produce aerosol particles having less than 5% drug degradation products. In a kit aspect of the present invention, a kit for delivering lidocaine, verapamil, diltiazem, isometheptene, or lisuride through an inhalation route is provided which comprises: a) a thin coating of a lidocaine, verapamil, diltiazem, isometheptene, or lisuride composition and b) a device for dispensing said thin coating as a condensation aerosol.
1. A condensation aerosol for delivery of a drug selected from the group consisting of lidocaine, verapamil, diltiazem, isometheptene and lisuride,
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. The condensation aerosol according to claim 1 , wherein the condensation aerosol is characterized by less than 2.5% drug degradation products by weight.
5. A method of producing a drug selected from the group consisting of lidocaine, verapamil, diltiazem, isometheptene and lisuride 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.
6. The method according to claim 5 , wherein the condensation aerosol is formed at a rate greater than 10 9 particles per second.
7. The method according to claim 6 , wherein the condensation aerosol is formed at a rate greater than 10 10 particles per second.
8. The condensation aerosol according to claim 1 , wherein the condensation aerosol is characterized by an MMAD of 0.1 to 5 microns.
9. The condensation aerosol according to claim 1 , wherein the condensation aerosol is characterized by an MMAD of less than 3 microns.
10. The condensation aerosol according to claim 9 , wherein the condensation aerosol is characterized by an MMAD of about 0.2 and 3 microns.
11. The condensation aerosol according to claim 1 , wherein the condensation aerosol is characterized by less than 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 lidocaine.
14. The condensation aerosol according to claim 1 , wherein the drug is verapamil.
15. The condensation aerosol according to claim 1 , wherein the drug is diltiazem.
16. The condensation aerosol according to claim 1 , wherein the drug is isometheptene.
17. The condensation aerosol according to claim 1 , wherein the drug is lisuride.
18. The method according to claim 5 , wherein the condensation aerosol is characterized by an MMAD of 0.1 to 5 microns.
19. The method according to claim 5 , wherein the condensation aerosol is characterized by an MMAD of less than 3 microns.
20. The method according to claim 5 , wherein the condensation aerosol is characterized by an MMAD of about 0.2 to about 3 microns.
21. The method according to claim 5 , wherein the condensation aerosol is characterized by less than 5% drug degradation products by weight.
22. The method according to claim 21 , wherein the condensation aerosol is characterized by less than 2.5% drug degradation products by weight.
23. The method according to claim 5 , wherein the solid support is a metal foil.
24. The method according to claim 5 , wherein the drug is lidocaine.
25. The method according to claim 5 , wherein the drug is verapamil.
26. The method according to claim 5 , wherein the drug is diltiazem.
27. The method according to claim 5 , wherein the drug is isometheptene.
28. The method according to claim 5 , wherein the drug is lisuride.
29. A condensation aerosol for delivery of lidocaine, wherein the condensation aerosol is formed by heating a thin layer containing lidocaine, on a solid support, to produce a vapor of lidocaine, and condensing the vapor to form a condensation aerosol characterized by less than 5% lidocaine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
30. A condensation aerosol for delivery of verapamil, wherein the condensation aerosol is formed by heating a thin layer containing verapamil, on a solid support, to produce a vapor of verapamil, and condensing the vapor to form a condensation aerosol characterized by less than 5% verapamil degradation products by weight, and an MMAD of about 0.2 to 3 microns.
31. A condensation aerosol for delivery of diltiazem, wherein the condensation aerosol is formed by heating a thin layer containing diltiazem, on a solid support, to produce a vapor of diltiazem, and condensing the vapor to form a condensation aerosol characterized by less than 5% diltiazem degradation products by weight, and an MMAD of about 0.2 to 3 microns.
32. A condensation aerosol for delivery of isometheptene, wherein the condensation aerosol is formed by heating a thin layer containing isometheptene, on a solid support, to produce a vapor of isometheptene, and condensing the vapor to form a condensation aerosol characterized by less than 5% isometheptene degradation products by weight, and an MMAD of about 0.2 to 3 microns.
33. A condensation aerosol for delivery of lisuride, wherein the condensation aerosol is formed by heating a thin layer containing lisuride, on a solid support, to produce a vapor of lisuride, and condensing the vapor to form a condensation aerosol characterized by less than 5% lisuride degradation products by weight, and an MMAD of about 0.2 to 3 microns.
34. A method of producing lidocaine in an aerosol form comprising:
a. heating a thin layer containing lidocaine, on a solid support, to produce a vapor of lidocaine, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% lidocaine degradation products by weight, and an MMAD of about 0.2 to about 3 microns.
35. A method of producing verapamil in an aerosol form comprising:
a. heating a thin layer containing verapamil, on a solid support, to produce a vapor of verapamil, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% verapamil degradation products by weight, and an MMAD of about 0.2 to about 3 microns.
36. A method of producing diltiazem in an aerosol form comprising:
a. heating a thin layer containing diltiazem, on a solid support, to produce a vapor of diltiazem, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% diltiazem degradation products by weight, and an MMAD of about 0.2 to about 3 microns.
37. A method of producing isometheptene in an aerosol form comprising:
a. heating a thin layer containing isometheptene, on a solid support, to produce a vapor of isometheptene, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% isometheptene degradation products by weight, and an MMAD of about 0.2 to about 3 microns.
38. A method of producing lisuride in an aerosol form comprising:
a. heating a thin layer containing lisuride, on a solid support, to produce a vapor of lisuride, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% lisuride degradation products by weight, and an MMAD of about 0.2 to about 3 microns.