Delivery of beta-blockers through an inhalation route
View Patent ↗The present invention relates to aerosols containing of atenolol, pindolol, esmolol, propranolol, or metoprolol that are used in inhalation therapy. In a method aspect of the present invention, of atenolol, pindolol, esmolol, propranolol, or metoprolol is administered to a patient through an inhalation route. The method comprises: a) heating a thin layer of atenolol, pindolol, esmolol, propranolol, or metoprolol, 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 of atenolol, pindolol, esmolol, propranolol, or metoprolol through an inhalation route is provided which comprises: a) a thin coating of an atenolol, pindolol, esmolol, propranolol, or metoprolol 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 atenolol, pindolol, esmolol, propranolol, and metoprolol
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 atenolol, pindolol, esmolol, propranolol, and metoprolol, 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 and about 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 atenolol.
14. The condensation aerosol according to claim 1 , wherein the drug is pindolol.
15. The condensation aerosol according to claim 1 , wherein the drug is esmolol.
16. The condensation aerosol according to claim 1 , wherein the drug is propranolol.
17. The condensation aerosol according to claim 1 , wherein the drug is metoprolol.
18. The method according to claim 4 , wherein the condensation aerosol is characterized by an MMAD of 0.1 to 5 microns.
19. The method according to claim 4 , wherein the condensation aerosol is characterized by an MMAD of less than 3 microns.
20. The method according to claim 4 , wherein the condensation aerosol is characterized by an MMAD of about 0.2 to about 3 microns.
21. The method according to claim 4 , 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 4 , wherein the solid support is a metal foil.
24. The method according to claim 4 , wherein the drug is atenolol.
25. The method according to claim 4 , wherein the drug is pindolol.
26. The method according to claim 4 , wherein the drug is esmolol.
27. The method according to claim 4 , wherein the drug is propranolol.
28. The method according to claim 4 , wherein the drug is metoprolol.
29. A condensation aerosol for delivery of atenolol, wherein the condensation aerosol is formed by heating a thin layer containing atenolol, on a solid support, to produce a vapor of atenolol, and condensing the vapor to form a condensation aerosol characterized by less than 5% atenolol degradation products by weight, and an MMAD of about 0.2 to about 3 microns.
30. A condensation aerosol for delivery of pindolol, wherein the condensation aerosol is formed by heating a thin layer containing pindolol, on a solid support, to produce a vapor of pindolol, and condensing the vapor to form a condensation aerosol characterized by less than 5% pindolol degradation products by weight, and an MMAD of about 0.2 to about 3 microns.
31. A condensation aerosol for delivery of esmolol, wherein the condensation aerosol is formed by heating a thin layer containing esmolol, on a solid support, to produce a vapor of esmolol, and condensing the vapor to form a condensation aerosol characterized by less than 5% esmolol degradation products by weight, and an MMAD of about 0.2 to about 3 microns.
32. A condensation aerosol for delivery of propranolol, wherein the condensation aerosol is formed by heating a thin layer containing propranolol, on a solid support, to produce a vapor of propranolol, and condensing the vapor to form a condensation aerosol characterized by less than 5% propranolol degradation products by weight, and an MMAD of about 0.2 to about 3 microns.
33. A condensation aerosol for delivery of metoprolol, wherein the condensation aerosol is formed by heating a thin layer containing metoprolol, on a solid support, to produce a vapor of metoprolol, and condensing the vapor to form a condensation aerosol characterized by less than 5% metoprolol degradation products by weight, and an MMAD of about 0.2 to about 3 microns.
34. A method of producing atenolol in an aerosol form comprising:
a. heating a thin layer containing atenolol, on a solid support, to produce a vapor of atenolol, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% atenolol degradation products by weight, and an MMAD of about 0.2 to about 3 microns.
35. A method of producing pindolol in an aerosol form comprising:
a. heating a thin layer containing pindolol, on a solid support, to produce a vapor of pindolol, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% pindolol degradation products by weight, and an MMAD of about 0.2 to about 3 microns.
36. A method of producing esmolol in an aerosol form comprising:
a. heating a thin layer containing esmolol, on a solid support, to produce a vapor of esmolol, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% esmolol degradation products by weight, and an MMAD of about 0.2 to about 3 microns.
37. A method of producing propranolol in an aerosol form comprising:
a. heating a thin layer containing propranolol, on a solid support, to produce a vapor of propranolol, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% propranolol degradation products by weight, and an MMAD of about 0.2 to about 3 microns.
38. A method of producing metoprolol in an aerosol form comprising:
a. heating a thin layer containing metoprolol, on a solid support, to produce a vapor of metoprolol, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% metoprolol degradation products by weight, and an MMAD of about 0.2 to about 3 microns.