Details for Patent: 7,048,909

Title:	Delivery of beta-blockers through an inhalation route
Abstract:	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.
Inventor(s):	Rabinowitz; Joshua D. (Mountain View, CA), Zaffaroni; Alejandro C. (Atherton, CA)
Assignee:	Alexza Pharmaceuticals, Inc. (Palo Alto, CA)
Filing Date:	Feb 09, 2004
Application Number:	10/775,586
Claims:	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.sup.9 particles per second. 3. The condensation aerosol according to claim 2, wherein the condensation aerosol is formed at a rate greater than 10.sup.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.sup.9 particles per second. 6. The method according to claim 5, wherein the condensation aerosol is formed at a rate greater than 10.sup.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.