Delivery of diazepam through an inhalation route

• US 7,045,119 B2
• Filed: 03/03/2004
• Issued: 05/16/2006
• Est. Priority Date: 11/09/2001
• Status: Expired due to Fees

• Current Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Original Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Inventors: Rabinowitz, Joshua D., Zaffaroni, Alejandro C.
• Primary Examiner(s): Kunz, Gary
• Assistant Examiner(s): Haghighatian, Mina
• Application Number:
  US10/792,001
• Publication Number:
  US 20040171609A1
• Time in Patent Office: 804 Days
• Field of Search: 424/45, 424/46, 424/489, 424/499, 514/220, 514/958, 128/200.24, 128/204.18, 128/200.14, 128/203.15
• US Class Current: 424/45
• CPC Class Codes: A61K 31/5513 1,4-Benzodiazepines, e.g. diazepam or clozapine
• CPC Class Codes: A61K 9/007 Pulmonary tract; Aromatherapy
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M

Abstract

The present invention relates to the delivery of compounds for the treatment of anxiety disorders and symptoms of such disorders through an inhalation route. Specifically, it relates to aerosols containing that are used in inhalation therapy. In a method aspect of the present invention, diazepam is administered to a patient through an inhalation route. The method comprises: a) heating a composition, comprising diazepam to form a vapor; and, b) allowing the vapor to cool, thereby forming a condensation aerosol with less than 5% of the drug degradation products. In a kit aspect of the present invention, a kit for delivering diazepam through an inhalation route is provided which comprises: a) a thin coating of a diazepam composition; and, b) a device for dispending said thin coating as a condensation aerosol

Claims

1. A method of treating anxiety disorders or symptoms in a patient comprising administering a therapeutic amount of a diazepam condensation aerosol to the patient by inhalation,

wherein the condensation aerosol is formed by heating a thin layer containing diazepam, on a solid support, to produce a vapor of diazepam, and condensing the vapor to form a condensation aerosol characterized by less than 10% diazepam degradation products by weight, and an MMAD of less than 5 microns.

2. The method according to claim 1, wherein the condensation aerosol is characterized by an MMAD of less than 3 microns.

3. The method according to claim 1, wherein the condensation aerosol is formed at a rate greater than 0.5 mg/second.

4. The method according to claim 1, wherein the therapeutic amount of the diazepam condensation aerosol comprises between 0.2 mg and 20 mg of diazepam delivered in a single inspiration.

5. The method according to claim 1, wherein peak plasma diazepam concentration is reached in less than 0.1 hours.

6. The method according to claim 1, wherein at least 50% by weight of the condensation aerosol is amorphous in form.

16. The method according to claim 1, wherein the condensation aerosol is characterized by an MMAD of 0.1 to 5 microns.

17. The method according to claim 2, wherein the condensation aerosol is characterized by an MMAD of about 0.2 to about 3 microns.

18. The method according to claim 1, wherein the thin layer has a thickness between 1.3 and 5.1 microns.

7. A method of administering a diazepam condensation aerosol to a patient comprising administering the diazepam condensation aerosol to the patient by inhalation,

wherein the diazepam condensation aerosol is formed by heating a thin layer containing diazepam, on a solid support, to produce a vapor of diazepam, and condensing the vapor to form a condensation aerosol characterized by less than 10% diazepam degradation products by weight, and an MMAD of less than 5 microns.

8. A kit for delivering a diazepam condensation aerosol comprising:

a. a thin layer containing diazepam, on a solid support, and

b. a device for providing the condensation aerosol, wherein the condensation aerosol is formed by heating the thin layer to produce a vapor of diazepam, and condensing the vapor to form a condensation aerosol characterized by less than 10% diazepam degradation products by weight, and an MMAD of less than 5 microns.

9. The kit according to claim 8, wherein the device comprises:

a. a flow through enclosure containing the solid support,

b. a power source that can be activated to heat the solid support, and

c. at least one portal through which air can be drawn by inhalation,

wherein activation of the power source is effective to produce a vapor of diazepam, and drawing air through the enclosure is effective to condense the vapor to form the condensation aerosol.

10. The kit according to claim 9, wherein the heat for heating the solid support is generated by an exothermic chemical reaction.

11. The kit according to claim 10, wherein the exothermic chemical reaction is oxidation of combustible materials.

12. The kit according to claim 9, wherein the heat for heating the solid support is generated by passage of current through an electrical resistance element.

13. The kit according to claim 9, wherein the solid support has a surface area dimensioned to accommodate a therapeutic dose of diazepam.

14. The kit according to claim 8, wherein peak plasma diazepam concentration is reached in less than 0.1 hours.

15. The kit according to claim 8, further including instructions for use.

19. The kit according to claim 8, wherein the condensation aerosol is characterized by an MMAD of less than 3 microns.

20. The kit according to claim 8, wherein the condensation aerosol is characterized by an MMAD of 0.1 to 5 microns.

21. The kit according to claim 23, wherein the condensation aerosol is characterized by an MMAD of about 0.2 to about 3 microns.

22. The kit according to claim 8, wherein the thin layer has a thickness between 1.3 and 5.1 microns.

23. The kit according to claim 9, wherein the solid support has a surface to mass ratio of greater than 1 cm² per gram.

24. The kit according to claim 9, wherein the solid support has a surface to volume ratio of greater than 100 per meter.

25. The kit according to claim 9, wherein the solid support is a metal foil.

26. The kit according to claim 25, wherein the metal foil has a thickness of less than 0.25 mm.