Drug condensation aerosols and kits

• US 9,440,034 B2
• Filed: 11/13/2013
• Issued: 09/13/2016
• 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:
  US14/078,679
• Publication Number:
  US 20140060525A1
• Time in Patent Office: 1,035 Days
• US Class Current: 1/1
• 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 composition for delivery of loxapine comprising a condensation aerosol

a) wherein the condensation aerosol is formed by heating a thin film of loxapine thereof to produce a vapor, wherein said film is a solid and condensing the vapor to form a condensation aerosol comprising loxapine;

b) wherein the condensation aerosol comprises particles that are characterized by less than 10% loxapine degradation products by weight;

c) wherein the condensation aerosol has an MMAD of less than 5 microns.

2. A kit for delivering a condensation aerosol, the kit comprising:

a) a thin film of a loxapine composition comprising loxapine, on a solid support, wherein said film is a solid, and

b) a device for providing the condensation aerosol, wherein the condensation aerosol is formed by heating the loxapine composition to produce a vapor, and condensing the vapor to form a condensation aerosol comprising loxapine,

wherein the condensation aerosol comprises particles that are characterized by less than 10% loxapine degradation products by weight,

wherein the condensation aerosol has an MMAD of less than 5 microns.

3. A loxapine supply article comprising:

a substrate having a surface;

a layer of loxapine applied to the substrate surface, the layer of loxapine having a select thickness and a select surface area, the select thickness providing less than 10% degradation of loxapine and the select surface area providing a therapeutically effective loxapine dosage upon vaporization of the layer of loxapine, wherein said layer of loxapine is a solid.

4. A method of administering loxapine of a type administered orally or by injection in combination with a solvent or excipient to a patient for inhalation by the patient comprising:

a) determining a therapeutically effective dose of loxapine for administration as a condensation aerosol by inhalation by a patient;

b) providing a volume of loxapine sufficient to provide the therapeutically effective dose upon vaporization on a substrate without any excipient or solvent, wherein the loxapine is in solid form;

c) vaporizing loxapine;

d) condensing loxapine to produce a condensation aerosol; and

e) delivering the condensation aerosol to a patient for inhalation.

5. A method of making a condensation aerosol from loxapine of the type administered orally or by injection in combination with a solvent or excipient to a patient for inhalation by the patient comprising:

a) determining a therapeutically effective dose of loxapine for administration as a condensation aerosol by inhalation by a patient;

b) providing a volume of loxapine sufficient to provide the therapeutically effective dose upon vaporization on a substrate without any excipient or solvent, wherein the loxapine is in solid form;

c) vaporizing loxapine; and

d) condensing loxapine to produce a condensation aerosol.