Details for Patent: 6,740,307

Title:	Delivery of .beta.-blockers through an inhalation route
Abstract:	The present invention relates to the delivery of beta-blockers through an inhalation route. Specifically, it relates to aerosols containing atenolol, pindolol, esmolol, propranolol, or metoprolol that are used in inhalation therapy. In a composition aspect of the present invention, the aerosol comprises particles comprising at least 5 percent by weight of atenolol, pindolol, esmolol, propranolol, or metoprolol. In a method aspect of the present invention, one of atenolol, pindolol, esmolol, propranolol, or metoprolol is delivered to a mammal through an inhalation route. The method comprises: a) heating a composition, wherein the composition comprises at least 5 percent by weight of atenolol, pindolol, esmolol, propranolol, or metoprolol, to form a vapor; and, b) allowing the vapor to cool, thereby forming a condensation aerosol comprising particles, which is inhaled by the mammal. In a kit aspect of the present invention, a kit for delivering atenolol, pindolol, esmolol, propranolol, or metoprolol through an inhalation route to a mammal is provided which comprises: a) a composition comprising at least 5 percent by weight of atenolol, pindolol, esmolol, propranolol, or metoprolol; and, b) a device that forms a atenolol, pindolol, esmolol, propranolol, or metoprolol containing aerosol from the composition, for inhalation by the mammal.
Inventor(s):	Rabinowitz; Joshua D. (Mountain View, CA), Zaffaroni; Alejandro C. (Atherton, CA)
Assignee:	Alexza Molecular Delivery Corporation (Palo Alto, CA)
Filing Date:	May 20, 2002
Application Number:	10/152,652
Claims:	1. A composition for delivery of the drug atenolol, pindolol, esmolol, propranolol, or metoprolol comprising a condensation aerosol a) formed by volatilizing the drug under conditions effective to produce a heated vapor of the drug and condensing the heated vapor of the drug to form condensation aerosol particles, b) wherein said condensation aerosol particles are characterized by less than 5% drug degradation product, and c) wherein the aerosol MMAD is less than 3 microns. 2. The composition according to claim 1, wherein the drug is in a free base form. 3. The composition according to claim 1, wherein the condensation aerosol particles comprise less than 5 percent by weight of atenolol, pindolol, esmolol, propranolol, or metoprolol degradation products. 4. The composition according to claim 1, wherein the condensation aerosol particles comprise at least 90 percent by weight of atenolol, pindolol, esmolol, propranolol, or metoprolol. 5. The composition according to claim 4, wherein the condensation aerosol particles comprise at least 95 percent by weight of atenolol, pindolol, esmolol, propranolol, or metoprolol. 6. A method of producing a beta-blocker drug in an aerosol form comprising: a) volatilizing a beta-blocker drug under conditions effective to produce a heated vapor of the drug, and b) during said volatilizing, passing air through the heated vapor to produce aerosol particles of the drug comprising less than 5% drug degradation products and an aerosol having an MMAD less than 3 .mu.m. 7. The method according to claim 6, wherein the beta-blocker drug is selected from the group consisting of atenolol, pindolol, esmolol, propranolol, or metoprolol. 8. The method according to claim 6, wherein the aerosol particles are formed at a rate of greater than 0.5 mg/sec. 9. The method according to claim 6, wherein the aerosol particles comprise less than 5 percent by weight of atenolol, pindolol, esmolol, propranolol, or metoprolol degradation products. 10. The method according to claim 6 wherein the aerosol particles comprise at least 90 percent by weight of atenolol, pindolol, esmolol, propranolol, or metoprolol. 11. The method according to claim 10, wherein the aerosol particles comprise at least 95 percent by weight of atenolol, pindolol, esmolol, propranolol, or metoprolol. 12. The method according to claim 6, wherein said volatilizing includes heating a thin layer which includes the beta-blocker drug and which is on a solid support having the surface texture of a metal foil, to a temperature sufficient to volatilize the drug from the thin layer. 13. The method according to claim 12, wherein the thin layer which includes the beta-blocker drug on said solid support surface has a thickness between 5.2 and 6.5 microns. 14. A composition for delivery of a beta-blocker drug comprising a condensation aerosol a) formed by volatilizing a beta-blocker drug under conditions effective to produce a heated vapor of the drug and condensing the heated vapor of the drug to form condensation aerosol particles, b) wherein said condensation aerosol particles are characterized by less than 5% beta-blocker drug degradation products, and c) wherein the aerosol MMAD is less than 3 microns.