Details for Patent: 7,060,255

Title:	Delivery of alprazolam, estazolam, midazolam or triazolam through an inhalation route
Abstract:	The present invention relates to the delivery of alprazolam, estazolam, midazolam or triazolam through an inhalation route. Specifically, it relates to aerosols containing alprazolam, estazolam, midazolam or triazolam that are used in inhalation therapy. In a method aspect of the present invention, alprazolam, estazolam, midazolam or triazolam is administered to a patient through an inhalation route. The method comprises: a) heating a thin layer of alprazolam, estazolam, midazolam or triazolam, 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 alprazolam, estazolam, midazolam or triazolam through an inhalation route is provided which comprises: a) a thin coating of an alprazolam, estazolam, midazolam, or triazolam 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:	Jan 29, 2004
Application Number:	10/769,157
Claims:	1. A condensation aerosol for delivery of a drug selected from the group consisting of alprazolam, estazolam, midazolam and triazolam, 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 alprazolam, estazolam, midazolam and triazolam 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 to 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 thin layer has a thickness between 0.2 and 4.8 microns. 14. The condensation aerosol according to claim 1, wherein the drug is alprazolam. 15. The condensation aerosol according to claim 1, wherein the drug is estazolam. 16. The condensation aerosol according to claim 1, wherein the drug is midazolam. 17. The condensation aerosol according to claim 1, wherein the drug is triazolam. 18. The method according to claim 4, wherein the condensation aerosol is characterized by an MMAD of 0.2 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 thin layer has a thickness between 0.2 and 4.8 microns. 25. The method according to claim 4, wherein the drug is alprazolam. 26. The method according to claim 4, wherein the drug is estazolam. 27. The method according to claim 4, wherein the drug is midazolam. 28. The method according to claim 4, wherein the drug is triazolam. 29. A condensation aerosol for delivery of alprazolam, wherein the condensation aerosol is formed by heating a thin layer containing alprazolam, on a solid support, to produce a vapor of alprazolam, and condensing the vapor to form a condensation aerosol characterized by less than 5% alprazolam degradation products by weight, and an MMAD of about 0.2 to 3 microns. 30. A condensation aerosol for delivery of estazolam, wherein the condensation aerosol is formed by heating a thin layer containing estazolam, on a solid support, to produce a vapor of estazolam, and condensing the vapor to form a condensation aerosol characterized by less than 5% estazolam degradation products by weight, and an MMAD of about 0.2 to 3 microns. 31. A condensation aerosol for delivery of midazolam, wherein the condensation aerosol is formed by heating a thin layer containing midazolam, on a solid support, to produce a vapor of midazolam, and condensing the vapor to form a condensation aerosol characterized by less than 5% midazolam degradation products by weight, and an MMAD of about 0.2 to 3 microns. 32. A condensation aerosol for delivery of triazolam, wherein the condensation aerosol is formed by heating a thin layer containing triazolam, on a solid support, to produce a vapor of triazolam, and condensing the vapor to form a condensation aerosol characterized by less than 5% triazolam degradation products by weight, and an MMAD of about 0.2 to 3 microns. 33. A method of producing alprazolam in an aerosol form comprising: a. heating a thin layer containing alprazolam, on a solid support, to produce a vapor of alprazolam, and b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% alprazolam degradation products by weight, and an MMAD of about 0.2 to 3 microns. 34. A method of producing estazolam in an aerosol form comprising: a. heating a thin layer containing estazolam, on a solid support, to produce a vapor of estazolam, and b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% estazolam degradation products by weight, and an MMAD of about 0.2 to 3 microns. 35. A method of producing midazolam in an aerosol form comprising: a. heating a thin layer containing midazolam, on a solid support, to produce a vapor characterized by less than 5% midazolam degradation products by weight, and an MMAD of about 0.2 to 3 microns. 36. A method of producing triazolam in an aerosol form comprising: a. heating a thin layer containing triazolam, on a solid support, to produce a vapor of triazolam, and b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% triazolam degradation products by weight, and an MMAD of about 0.2 to 3 microns.