Delivery of aerosols containing small particles through an inhalation route

• US 20040096402A1
• Filed: 10/30/2003
• Published: 05/20/2004
• Est. Priority Date: 06/05/2001
• Status: Abandoned Application

• Current Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Original Assignee: Alexza Molecular Delivery Corporation (Grupo Ferrer Internacional SA)
• Inventors: Lloyd, Peter M., Hodges, Craig C., Wensley, Martin J., Mufson, Daniel, Rogers, Daniel D.
• Application Number:
  US10/696,959
• Publication Number:
  US 20040096402A1
• Time in Patent Office: Days
• US Class Current: 424/46
• CPC Class Codes: A61K 31/235 having an aromatic ring attached to a carboxyl group
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• 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
• CPC Class Codes: A61M 11/001 Particle size control
• CPC Class Codes: A61M 11/02 operated by air or other gas pressure applied to the liquid or other product to be sprayed or atomised sprayers for horticulture A01G, A01H; killing insects A01M; air humidifying by nozzles F24F6/14, F24F6/18; cooling by spraying F28B, F28C
• CPC Class Codes: A61M 11/044 with electrodes immersed in the liquid
• CPC Class Codes: A61M 15/00 Inhalators drug delivery in endotracheal tubes A61M16/04
• CPC Class Codes: A61M 15/0028 using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
• CPC Class Codes: A61M 16/109 the humidifying liquid or the beneficial agent
• CPC Class Codes: A61M 2016/0039 in the inspiratory circuit
• CPC Class Codes: A61M 2205/3606 cooled
• CPC Class Codes: A61M 2205/3653 by Joule effect, i.e. electric resistance
• CPC Class Codes: A61M 2205/368 by electromagnetic radiation, e.g. IR waves
• CPC Class Codes: A61M 2205/50 with microprocessors or computers
• CPC Class Codes: A61P 23/00 Anaesthetics
• CPC Class Codes: B05B 17/04 operating with special methods
• CPC Class Codes: B05B 7/1686 involving vaporisation of the material to be sprayed or of an atomising-fluid-generating product

Abstract

The present invention relates to the inhalation delivery of aerosols containing small particles. Specifically, it relates to the delivery of drug containing aerosols having particles with a mass median aerodynamic diameter less than 1μ for inhalation therapy. In an aspect of the present invention the drug containing aerosol comprises particles having a mass median aerodynamic diameter between 10 nm and 1μ. Preferably, the particles have a mass median aerodynamic diameter between 10 nm and 900 nm. More preferably, the particles have a mass median aerodynamic diameter between 10 nm and 800 nm, 10 nm and 700 nm, 10 nm and 600 nm, 10 nm and 500 nm, 10 nm and 400 nm, 10 nm and 300 nm, 10 nm and 200 nm, or 10 nm and 100 nm.

Claims

1. A method for preparing an aerosol of particles having a mass median aerodynamic diameter of less than 1 μ

m comprising the steps of

a) depositing a compound composition on a substrate

b) heating said substrate to form a vapor of at least a portion of the composition

c) mixing the resulting vapor with a gas, in a ratio to form an aerosol with a mass median aerodynamic diameter of less than 1 μ

m when a stable number concentration of particles in the gas is reached.

2. The method of claim 1, wherein said mixing involves passing a gas across the surface of said composition during heating.

3. The method of claim 1, wherein said mixing involves passing a gas with turbulence across the surface of said composition during heating.

4. The method of claim 3, wherein said gas is air.

5. The method of claim 1, wherein the composition is deposited as a thin film.

6. Method of claim 5, wherein the thin film is of a thickness of less than 10 microns.

7. The method of claim 6, wherein the thin film is vaporized at a rate of 0.5 to 2 mg/sec.

8. The method of claim 1, wherein said mass median aerodynamic diameter is between 10 nm and 900 nm.

9. The method of claim 1, wherein said mass median aerodynamic diameter is between 10 nm and 500 nm.

10. The method of claim 1, wherein said mass median aerodynamic diameter is between 10 nm and 100 nm

11. The method of claim 1, wherein said vaporization is complete in less than 2 seconds.

12. The method of claim 1, wherein said heating is at a rate of at least 1000°

C./second.

13. The method of claim 1, wherein the substrate is metallic.

14. The method of claim 13, wherein the metallic substrate is stainless steel.

15. The method of claim 1, wherein said heating is resistive or inductive.

16. The method of claim 1, wherein the mass median aerodynamic diameter has a geometric standard deviation of less than 2.

17. The method of claim 1, wherein the stable number concentration of particles in the gas is about 10⁹ particles/mL.