Delivery of diazepam through an inhalation route

• US 6,805,853 B2
• Filed: 05/15/2002
• Issued: 10/19/2004
• Est. Priority Date: 11/09/2001
• Status: Expired due to Fees

• Current Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Original Assignee: Alexza Molecular Delivery Corporation (Grupo Ferrer Internacional SA)
• Inventors: Rabinowitz, Joshua D., Zaffaroni, Alejandro C.
• Primary Examiner(s): Hartley, Michael G.
• Assistant Examiner(s): Haghighatian, Mina
• Application Number:
  US10/150,056
• Publication Number:
  US 20030091511A1
• Time in Patent Office: 888 Days
• Field of Search: 424/45, 424/46, 514/220, 128/200.24, 128/204.18
• 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 diazepam through an inhalation route. Specifically, it relates to aerosols containing diazepam 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 diazepam. In a method aspect of the present invention, diazepam 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 diazepam, 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 diazepam through an inhalation route to a mammal is provided which comprises: a) a composition comprising at least 5 percent by weight of diazepam; and, b) a device that forms a diazepam containing aerosol from the composition, for inhalation by the mammal.

Claims

1. A composition for delivery of diazepam comprising a condensation aerosol

a) formed by volatilizing the diazepam under conditions effective to produce a heated vapor of the diazepam and condensing the heated vapor of the diazepam to form condensation aerosol particles,

b) wherein said condensation aerosol particles are characterized by less than 5% diazepam degradation products, and

c) wherein the aerosol MMAD is less than 3 microns.

2. The composition according to claim 1, wherein the condensation aerosol has a mass of at least 0.10 mg.

3. The composition according to claim 1, wherein the condensation aerosol particles comprise less than 2.5 percent by weight of diazepam degradation products.

4. The composition according to claim 1, wherein the condensation aerosol particles comprise at least 90 percent by weight of diazepam.

5. The composition according to claim 4, wherein the condensation aerosol has a mass median aerodynamic diameter less than 2 microns.

6. The composition according to claim 5, wherein the condensation aerosol particles comprise at least 97 percent by weight of diazepam.

7. A method of producing diazepam in an aerosol form comprising:

a) volatilizing diazepam 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 diazepam comprising less than 5% diazepam degradation products and an aerosol having an MMAD less than 3 μ

m.

8. The method according to claim 7, wherein said volatilizing includes heating a thin layer which includes the diazepam and which is on a solid support having the surface texture of a metal foil, to a temperature sufficient to volatilize the diazepam from the thin layer.

9. The method according to claim 7, wherein the aerosol has a mass of at least 0.10 mg.

10. The method according to claim 7, wherein the aerosol particles are formed at a rate of greater than 0.85 mg/sec.

11. The method according to claim 7, wherein the aerosol particles comprise less than 2.5 percent by weight of diazepam degradation products.

12. The method according to claim 7, wherein the aerosol particles comprise at least 90 percent by weight of diazepam.

13. The method according to claim 12, wherein the aerosol has a mass median aerodynamic diameter less than 2 microns.

14. The method according to claim 13, wherein the aerosol particles comprise at least 97 percent by weight of diazepam.

15. The method according to claim 8, wherein the thin layer which includes diazepam on said solid support surface has a thickness between 1.3 and 5.1 microns.