Rapid-heating drug delivery article and method of use

• US 7,645,442 B2
• Filed: 08/04/2003
• Issued: 01/12/2010
• Est. Priority Date: 05/24/2001
• Status: Active Grant

• Current Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Original Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Inventors: Song, Soonho, Tom, Curtis, Hale, Ron L., Lloyd, Peter M., Quintana, Reynaldo J., Rabinowitz, Joshua D., Myers, Daniel J., Wensley, Martin J., Solas, Dennis W., Lu, Amy
• Primary Examiner(s): Haghighatian; Mina
• Application Number:
  US10/633,876
• Publication Number:
  US 20070028916A1
• Time in Patent Office: 2,353 Days
• Field of Search: 424/45, 424/46, 424/434, 424/489, 424/499, 128/200.14, 128/200.24, 128/203.15, 514/958
• US Class Current: 424/45
• 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 11/041 using heaters
• CPC Class Codes: A61M 11/042 electrical
• CPC Class Codes: A61M 11/047 by exothermic chemical reaction
• CPC Class Codes: A61M 15/002 with air flow regulating means
• 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 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: 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

A device, method, and system for producing a condensation aerosol are disclosed. The device includes a chamber having an upstream opening and a downstream opening which allow gas to flow through the chamber, and a heat-conductive substrate located at a position between the upstream and downstream openings. Formed on the substrate is a drug composition film containing a therapeutically effective dose of a drug when the drug is administered in aerosol form. A heat source in the device is operable to supply heat to the substrate to produce a substrate temperature greater than 300° C., and to substantially volatilize the drug composition film from the substrate in a period of 2 seconds or less. The device produces an aerosol containing less than about 10% by weight drug composition degradation products and at least 50% of the drug composition of said film.

Claims

1. A device for producing a condensation aerosol comprising

(a) a chamber comprising an upstream opening and a downstream opening, the openings allowing gas to flow therethrough

(b) a heat-conductive substrate, the substrate located at a position between the upstream and downstream openings,

(c) a drug composition film on the substrate, the film comprising a therapeutically effective dose of a drug when the drug is administered in aerosol form

(d) a heat source for supplying heat to said substrate to produce a substrate temperature greater than 300°

C., and to substantially volatilize the drug composition film from the substrate in a period of 2 seconds or less, and

(e) means for producing an air flow across the substrate producing aerosol particles by condensation,

wherein the device produces a condensation aerosol containing about 10% or less by weight drug composition degradation products and at least 50% of the drug composition of said film.

2. The device of claim 1, further comprising a mechanism for initiating said heat source.

3. The device of claim 1, wherein said substrate has an impermeable surface.

4. The device of claim 1, wherein said substrate has a contiguous surface area of greater than 1 mm² and a material density of greater than 0.5 g/cc.

5. The device of claim 1, wherein the film has a thickness between 0.05 and 20 microns.

6. The device of claim 5, wherein the thickness of the film is selected to allow the drug composition to volatilize from the substrate with about 5% or less by weight drug composition degradation products.

7. The device of claim 6, wherein the drug composition is one that when vaporized from a film on an impermeable surface of a heat conductive substrate, the aerosol exhibits an increasing level of drug composition degradation products with increasing film thicknesses.

8. The device of claim 5, wherein said drug composition comprises a drug selected from the group consisting of the following, and a film thickness within the range disclosed for said drug:

(1) alprazolam, film thickness between 0.1 and 10 μ

m;

(2) amoxapine, film thickness between 2 and 20 μ

m;

(3) atropine, film thickness between 0.1 and 10 μ

m;

(4) bumetanide film thickness between 0.1 and 5 μ

m;

(5) buprenorphine, film thickness between 0.05 and 10 μ

m;

(6) butorphanol, film thickness between 0.1 and 10 μ

m;

(7) clomipramine, film thickness between 1 and 8 μ

m;

(8) donepezil, film thickness between 1 and 10 μ

m;

(9) hydromorphone, film thickness between 0.05 and 10 μ

m;

(10) loxapine, film thickness between 1 and 20 μ

m;

(11) midazolam, film thickness between 0.05 and 20 μ

m;

(12) morphine, film thickness between 0.2 and 10 μ

m;

(13) nalbuphine, film thickness between 0.2 and 5 μ

m;

(14) naratriptan, film thickness between 0.2 and 5 μ

m;

(15) olanzapine, film thickness between 1 and 20 μ

m;

(16) paroxetine, film thickness between 1 and 20 μ

m;

(17) prochlorperazine, film thickness between 0.1 and 20 μ

m;

(18) quetiapine, film thickness between 1 and 20 μ

m;

(19) sertraline, film thickness between 1 and 20 μ

m;

(20) sibutramine, film thickness between 0.5 and 2 μ

m;

(21) sildenafil, film thickness between 0.2 and 3 μ

m;

(22) sumatriptan, film thickness between 0.2 and 6 μ

m;

(23) tadalafil, film thickness between 0.2 and 5 μ

m;

(24) vardenafil, film thickness between 0.1 and 2 μ

m;

(25) venlafaxine, film thickness between 2 and 20 μ

m;

(26) zolpidem, film thickness between 0.1 and 10 μ

m;

(27) apomorphine HCl, film thickness between 0.1 and 5 μ

m;

(28) celecoxib, film thickness between 2 and 20 μ

m;

(29) ciclesonide, film thickness between 0.05 and 5 μ

m;

(30) eletriptan, film thickness between 0.2 and 20 μ

m;

(31) parecoxib, film thickness between 0.5 and 2 μ

m;

(32) valdecoxib, film thickness between 0.5 and 10 μ

m;

(33) fentanyl, film thickness between 0.05 and 5 μ

m.

9. The device of claim 1, wherein said heat source substantially volatilizes the drug composition film from the substrate within a period of less than 0.5 seconds.

10. The device of claim 1, wherein said heat source comprises an ignitable solid chemical fuel disposed adjacent to an interior surface of the substrate, wherein the ignition of said fuel is effective to vaporize the drug composition film.

11. The device of claim 1, wherein said heat source for supplying heat to said substrate produces a substrate temperature greater than 350°

C.

12. A method for producing a condensation aerosol comprising (a) heating to a temperature greater than 300°

C. a heat-conductive substrate having a drug composition film on the surface, the film comprising a therapeutically effective dose of a drug when the drug is administered in aerosol form;

(b) substantially volatilizing the drug composition film from the substrate in a period of 2 seconds or less, and

(c) flowing air across the volatilized drug composition, under conditions to produce a condensation aerosol containing less than 10% by weight drug composition degradation products and at least 50% of the drug composition in said film.

13. The method of claim 12, wherein said substrate has an impermeable surface.

14. The method of claim 12, wherein said substrate has a contiguous surface area of greater than 1 mm² and a material density of greater than 0.5 g/cc.

15. The method of claim 12, wherein the film has a thickness between 0.05 and 20 microns.

16. The method of claim 15, wherein the thickness of the film is selected to allow the drug composition to volatilize from the substrate with about 10% or less by weight drug composition degradation products.

17. The method of claim 16, wherein the drug composition is one that when vaporized from a film on an impermeable surface of a heat conductive substrate, the aerosol exhibits an increasing level of drug composition degradation products with increasing film thicknesses.

18. The method of claim 12, wherein said drug composition comprises a drug selected from the group consisting of the following, and a film thickness within the range disclosed for said drug:

(1) alprazolam, film thickness between 0.1 and 10 μ

m;

(2) amoxapine, film thickness between 2 and 20 μ

m;

(3) atropine, film thickness between 0.1 and 10 μ

m;

(4) bumetanide film thickness between 0.1 and 5 μ

m;

(5) buprenorphine, film thickness between 0.05 and 10 μ

m;

(6) butorphanol, film thickness between 0.1 and 10 μ

m;

(7) clomipramine, film thickness between 1 and 8 μ

m;

(8) donepezil, film thickness between 1 and 10 μ

m;

(9) hydromorphone, film thickness between 0.05 and 10 μ

m;

(10) loxapine, film thickness between 1 and 20 μ

m;

(11) midazolam, film thickness between 0.05 and 20 μ

m;

(12) morphine, film thickness between 0.2 and 10 μ

m;

(13) nalbuphine, film thickness between 0.2 and 5 μ

m;

(14) naratriptan, film thickness between 0.2 and 5 μ

m;

(15) olanzapine, film thickness between 1 and 20 μ

m;

(16) paroxetine, film thickness between 1 and 20 μ

m;

(17) prochlorperazine, film thickness between 0.1 and 20 μ

m;

(18) quetiapine, film thickness between 1 and 20 μ

m;

(19) sertraline, film thickness between 1 and 20 μ

m;

(20) sibutramine, film thickness between 0.5 and 2 μ

m;

(21) sildenafil, film thickness between 0.2 and 3 μ

m;

(22) sumatriptan, film thickness between 0.2 and 6 μ

m;

(23) tadalafil, film thickness between 0.2 and 5 μ

m;

(24) vardenafil, film thickness between 0.1 and 2 μ

m;

(25) venlafaxine, film thickness between 2 and 20 μ

m;

(26) zolpidem, film thickness between 0.1 and 10 μ

m;

(27) apomorphine HCl, film thickness between 0.1 and 5 μ

m;

(28) celecoxib, film thickness between 2 and 20 μ

m;

(29) ciclesonide, film thickness between 0.05 and 5 μ

m;

(30) eletriptan, film thickness between 0.2 and 20 μ

m;

(31) parecoxib, film thickness between 0.5 and 2 μ

m;

(32) valdecoxib, film thickness between 0.5 and 10 μ

m; and

(33) fentanyl, film thickness between 0.05 and 5 μ

m.

19. The method of claim 12, wherein said substantially volatilizing the film is complete within a period of less than 0.5 seconds.

20. An assembly for use in a condensation aerosol device comprising

(a) a heat-conductive substrate having an interior surface and an exterior surface;

(b) a drug composition film on the substrate exterior surface, the film comprising a therapeutically effective dose of a drug when the drug is administered in aerosol form, and

(c) a heat source for supplying heat to said substrate to produce a substrate temperature greater than 300°

C. and to substantially volatilize the drug composition film from the substrate in a period of 2 seconds or less wherein the device produces a condensation aerosol containing about 10% or less by weight drug composition degradation products and at least 50% of the drug composition of said film.

21. The assembly of claim 20, wherein said substrate has an impermeable surface.

22. The assembly of claim 20, wherein said substrate surface has a contiguous surface area of greater than 1 mm² and a material density of greater than 0.5 g/cc.

23. The assembly of claim 20, wherein the film has a thickness between 0.05 and 20 microns.

24. The assembly of claim 23, wherein the thickness of the film is selected to allow the drug composition to volatilize from the substrate with about 5% or less by weight drug composition degradation products.

25. The assembly of claim 24, the drug composition is one that when vaporized from a film on an impermeable surface of a heat conductive substrate, the aerosol exhibits an increasing level of drug composition degradation products with increasing film thickness.

26. The assembly of claim 20, wherein said drug composition comprises a drug selected from the group consisting of the following, and a film thickness within the range disclosed for said drug:

(1) alprazolam, film thickness between 0.1 and 10 μ

m;

(2) amoxapine, film thickness between 2 and 20 μ

m;

(3) atropine, film thickness between 0.1 and 10 μ

m;

(4) bumetanide film thickness between 0.1 and 5 μ

m;

(5) buprenorphine, film thickness between 0.05 and 10 μ

m;

(6) butorphanol, film thickness between 0.1 and 10 μ

m;

(7) clomipramine, film thickness between 1 and 8 μ

m;

(8) donepezil, film thickness between 1 and 10 μ

m;

(9) hydromorphone, film thickness between 0.05 and 10 μ

m;

(10) loxapine, film thickness between 1 and 20 μ

m;

(11) midazolam, film thickness between 0.05 and 20 μ

m;

(12) morphine, film thickness between 0.2 and 10 μ

m;

(13) nalbuphine, film thickness between 0.2 and 5 μ

m;

(14) naratriptan, film thickness between 0.2 and 5 μ

m;

(15) olanzapine, film thickness between 1 and 20 μ

m;

(16) paroxetine, film thickness between 1 and 20 μ

m;

(17) prochlorperazine, film thickness between 0.1 and 20 μ

m;

(18) quetiapine, film thickness between 1 and 20 μ

m;

(19) sertraline, film thickness between 1 and 20 μ

m;

(20) sibutramine, film thickness between 0.5 and 2 μ

m;

(21) sildenafil, film thickness between 0.2 and 3 μ

m;

(22) sumatriptan, film thickness between 0.2 and 6 μ

m;

(23) tadalafil, film thickness between 0.2 and 5 μ

m;

(24) vardenafil, film thickness between 0.1 and 2 μ

m;

(25) venlafaxine, film thickness between 2 and 20 μ

m;

(26) zolpidem, film thickness between 0.1 and 10 μ

m;

(27) apomorphine HCl, film thickness between 0.1 and 5 μ

m;

(28) celecoxib, film thickness between 2 and 20 μ

m;

(29) ciclesonide, film thickness between 0.05 and 5 μ

m;

(30) eletriptan, film thickness between 0.2 and 20 μ

m;

(31) parecoxib, film thickness between 0.5 and 2 μ

m;

(32) valdecoxib, film thickness between 0.5 and 10 μ

m; and

(33) fentanyl, film thickness between 0.05 and 5 μ

m.

27. The assembly of claim 20, wherein said heat source substantially volatilizes the drug composition film from the substrate within a period of less than 0.5 seconds.

28. The device of claim 20, wherein said heat source comprises an ignitable solid chemical fuel disposed adjacent to the interior surface of the substrate, wherein the ignition of said fuel is effective to vaporize the drug composition film.