Delivery of drug amines through an inhalation route

• US 20040009128A1
• Filed: 05/13/2003
• Published: 01/15/2004
• Est. Priority Date: 05/13/2002
• Status: Active Grant

• 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.
• Granted Patent: US 8,003,080 B2
• Time in Patent Office: Days
• US Class Current: 424/46
• 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 11/041 using heaters
• CPC Class Codes: A61M 15/00 Inhalators drug delivery in endotracheal tubes A61M16/04

Abstract

The present invention relates to the delivery of drug amines through an inhalation route. Specifically, it relates to aerosols containing drug amines that are used in inhalation therapy. In one aspect of the present invention, a method of delivering an amine drug in an aerosol form is provided. The method comprises: a) heating a coating, which includes an amine drug salt on a substrate contained in a device to a temperature sufficient to volatilize the amine drug from the coating, b) by said heating, forming an amine drug vapor, and c) during said heating, drawing air through said device, condensing said vapor to form aerosol particles containing less than 10% degradation products of the compound.

Claims

1. A method of selecting an amine drug salt suitable for use in forming a condensation aerosol, comprising

a. dissolving or suspending an amine drug salt in a solvent,

b. coating the suspended or dissolved amine drug salt on a substrate,

c. heating the coated substrate to form a compound vapor,

d. cooling the vapor to form aerosol particles,

e. collecting the aerosol particles,

f. analyzing the collected particles to determine the purity of the aerosol particles;

and

g. selecting the amine drug based on a decomposition index less than 0. 15.

2. The method of claim 1, wherein said substrate is metallic.

3. The method of claim 2, wherein said metallic substrate is aluminum foil or stainless steel.

4. The method of claim 2, wherein said heating is on a hot plate.

5. The method of claim 4, wherein said heating is to a temperature approximately about 300°

C.

6. The method of Claim 1, wherein said heating is resistance heating.

7. The method of claim 6, wherein said heating is to a temperature of approximately about 400°

C.

8. The method of claim 1, wherein the amine drug salt is selected from the group consisting of an antibiotic, anticonvulsant, antidepressant, antiemetic, antihistamine, antiparkinsonian drug, antipsychotic, anxiolytic, a drug for erectile dysfunction, a drug for migraine headache, a drug for the treatment of addiction, a muscle relaxant, a non-steroidal anti-inflammatory, an opioid, or other analgesic.

9. An aerosol comprising an amine drug from an amine drug salt selected by the method of claim 2, wherein said amine drug salt is vaporized and condensed to form amine drug aerosol particles having a mass median aerodynamic diameter between the range of 1 and 3, and has less than 10% amine drug decomposition products.

10. The aerosol of claim 9, wherein said amine drug salt has a molecular weight between 200 to 600.

11. The aerosol of claim 9, wherein said amine drug salt is selected from the group consisting of an antibiotic, anticonvulsant, antidepressant, antiemetic, antihistamine, antiparkinsonian drug, antipsychotic, anxiolytic, a drug for erectile dysfunction, a drug for migraine headache, a drug for the treatment of addiction, a muscle relaxant, a non-steroidal anti-inflammatory, an opioid, or other analgesic.

12. A method of delivering an amine drug in an aerosol form, comprising

a. heating a coating, which includes an amine drug salt on a substrate contained in a device to a temperature sufficient to volatilize the amine drug from the coating,

b. by said heating, forming a amine drug vapor, and

c. during said heating, drawing air through said device, condensing said vapor to form aerosol particles containing less than 10% degradation products of the compound.

13. The method according to claim 12, wherein said coating of amine drug salt has a thickness between about 0.2 and 20 μ

m.

14. The method according to claim 13, wherein said aerosol particles have a mass median aerodynamic diameter between about 1 and 3 microns.

15. The method of claim 14, wherein the amine drug salt is selected from the group consisting of an antibiotic, anticonvulsant, antidepressant, antiemetic, antihistamine, antiparkinsonian drug, antipsychotic, anxiolytic, a drug for erectile dysfunction, a drug for migraine headache, a drug for the treatment of addiction, a muscle relaxant, a non-steroidal anti-inflammatory, an opioid, or other analgesic.

16. The method according to claim 15, wherein said amine drug salt has a molecular weight between 200 to 600.

17. A thermal vapor comprising gas and amine drug aerosol particles,

a. wherein said gas comprises an acid halide vapor, organic acid vapor, or organic acid decomposition product vapor, and

b. wherein said amine drug aerosol particles

i. comprise at least 10 micrograms of an amine drug and less than 10% amine drug decomposition products relative to said total mass of amine drug in the particles, and

ii. have a mass median aerodynamic diameter in the range 1 to 5 micrometers.

18. The thermal vapor of claim 17, wherein said gas further comprises supersaturated drug amine vapor.

19. The thermal vapor of claim 18, wherein said supersaturated drug amine vapor has a temperature of greater than 200°

C.

20. The thermal vapor of claim 17, wherein said drug amine aerosol particles have a mass median aerodynamic diameter in the range 1 to 3 micrometers.

21. The thermal vapor of claim 17, wherein the amine drug is selected from the group consisting of an antibiotic, anticonvulsant, antidepressant, antiemetic, antihistamine, antiparkinsonian drug, antipsychotic, anxiolytic, a drug for erectile dysfunction, a drug for migraine headache, a drug for the treatment of addiction, a muscle relaxant, a non-steroidal anti-inflammatory, an opioid, or other analgesic.

22. A method of forming an effective human therapeutic inhalation dose of drug amine aerosol particles having less than 10% degradation products and a drug amine particle mass median aerodynamic diameter between about 1 and 5 micrometers, comprising

a) providing a drug delivery article comprising a body defining an interior flow-through chamber having upstream and down stream chamber ends and a drug supply unit contained within such chamber, wherein said drug supply unit comprises a heat-conductive substrate coated with a composition comprising at least a therapeutic amount of amine drug salt having a decomposition index less than 0.10;

b) heating said heat-conductive substrate to a temperature of greater than 200°

C. over a period of less than 5 seconds, thereby producing a vapor of a therapeutic dose of said amine drug salt; and

c) flowing a gas through said chamber thereby cooling said vapor to form drug amine aerosol particles.

23. The method according to claim 22, wherein the drug amine salt is a salt selected from the group consisting of an antibiotic, anticonvulsant, antidepressant, antiemetic, antihistamine, antiparkinsonian drug, antipsychotic, anxiolytic, a drug for erectile dysfunction, a drug for migraine headache, a drug for the treatment of addiction, a muscle relaxant, a non-steroidal anti-inflammatory, an opioid, or other analgesic.