Drug condensation aerosols and kits

• US 8,235,037 B2
• Filed: 05/08/2008
• Issued: 08/07/2012
• Est. Priority Date: 05/24/2001
• Status: Expired due to Term

• Current Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Original Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Inventors: Hale, Ron L., Hodges, Craig C., Lloyd, Peter M., Lu, Amy T., Myers, Daniel J., Rabinowitz, Joshua D., Wensley, Martin J., McKinney, Jeffrey A., Zaffaroni, Alejandro C.
• Primary Examiner(s): Haghighatian, Mina
• Application Number:
  US12/117,737
• Publication Number:
  US 20080311176A1
• Time in Patent Office: 1,552 Days
• Field of Search: 128/200.14, 128/200.16, 128/200.21, 128/200.24, 128/203.26, 128/203.15, 128/204.15, 424/45, 424/46, 424/489, 424/434
• US Class Current: 128/200.14
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/5415 ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
• CPC Class Codes: A61K 31/5517 condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
• CPC Class Codes: A61K 31/553 having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/007 Pulmonary tract; Aromatherapy
• CPC Class Codes: A61K 9/0078 for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
• CPC Class Codes: A61K 9/12 Aerosols; Foams A61K9/0043, A61K9/0056, A61K9/006, A61K9/0073 take precedence; spray-films A61K9/7015
• CPC Class Codes: A61M 11/002 by flow deviation causing inertial separation of transported particles
• CPC Class Codes: A61M 11/005 using ultrasonics spraying or atomising liquids using ultrasonic vibrations in general B05B17/06
• CPC Class Codes: A61M 11/04 operated by the vapour pressure of the liquid to be sprayed or atomised air-humidification, e.g. "room humidifiers" F24F6/00
• CPC Class Codes: A61M 11/041 using heaters
• CPC Class Codes: A61M 11/042 electrical
• CPC Class Codes: A61M 11/047 by exothermic chemical reaction
• CPC Class Codes: A61M 15/00 Inhalators drug delivery in endotracheal tubes A61M16/04
• CPC Class Codes: A61M 2207/00 Methods of manufacture, assembly or production
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia

Abstract

The present invention provides novel condensation aerosols for the treatment of disease and/or intermittent or acute conditions. These condensation aerosols have little or no pyrolysis degradation products and are characterized by having an MMAD of between 1-3 microns. These aerosols are made by rapidly heating a substrate coated with a thin film of drug having a thickness of between 0.05 and 20 μm, while passing a gas over the film, to form particles of a desirable particle size for inhalation. Kits comprising a drug and a device for producing a condensation aerosol are also provided. The device contained in the kit typically, has an element for heating the drug which is coated as a film on the substrate and contains a therapeutically effective dose of a drug when the drug is administered in aerosol form, and an element allowing the vapor to cool to form an aerosol. Also disclosed, are methods for using these aerosols and kits.

Claims

1. A drug supply article comprising:

a heat-conductive substrate having an impermeable surface;

a drug composition comprising the drug coated on at least a portion of the surface in the form of a film having a thickness; and

a heat source operable to supply heat to the substrate at a rate that achieves a temperature sufficient to vaporize all or a portion of the coated drug composition within a period of 2 seconds;

wherein the drug composition is vaporized followed by condensation of the vapor to form an aerosol;

wherein the aerosol drug composition comprises a therapeutically effective amount of the drug;

wherein the film has a thickness between 0.05 and 20 microns;

wherein the drug is selected from the group consisting of alprazolam, fentanyl, loxapine, prochlorperazine and zaleplon.

2. The drug supply article of claim 1, wherein the drug is in a free base form.

3. The drug supply article of claim 1, wherein the drug is in a salt form.

4. The drug supply article of claim 1, wherein the drug composition comprises only pure drug.

5. The drug supply article of claim 1, wherein the drug composition comprises a pharmaceutically acceptable excipient.

6. The drug supply article of claim 1, wherein the drug is alprazolam.

7. The drug supply article of claim 6, wherein the film thickness is between 0.1 and 10 microns.

8. The drug supply article of claim 1, wherein the drug is loxapine.

9. The drug supply article of claim 8, wherein the film thickness is between 1 and 20 microns.

10. The drug supply article of claim 1, wherein the drug is prochlorperazine.

11. The drug supply article of claim 10, wherein the film thickness is between 0.1 and 20 microns.

12. The drug supply article of claim 1, wherein the drug is zaleplon.

13. The drug supply article of claim 12, wherein the film thickness is between 0.1 and 15 microns.

14. The drug supply article of claim 1, wherein the drug is fentanyl.

15. The drug supply article of claim 14, wherein the film thickness is between 0.05 and 5 microns.