Aerosol drug delivery device incorporating percussively activated heat packages

• US 7,581,540 B2
• Filed: 08/12/2004
• Issued: 09/01/2009
• Est. Priority Date: 08/12/2004
• Status: Active Grant

• Current Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Original Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Inventors: Lei, Mingzu, Munzar, Patrik, Hale, Ron L., Lloyd, Peter M., Solas, Dennis W., Sharma, Krishnamohan, Stracker, Matthew D.
• Primary Examiner(s): Yu; Justine R
• Assistant Examiner(s): MATTER, KRISTEN CLARETTE
• Application Number:
  US10/917,720
• Publication Number:
  US 20060032501A1
• Time in Patent Office: 1,846 Days
• Field of Search: 514/343, 514/169, 514/953, 514/957, 514/965, 514492-505, 424/443, 424 40- 42, 131/194, 131/195, 131270-273, 128/200.14, 128/200.24, 128/202.21, 128/203.12, 128/203.14, 128/203.15, 128/203.17, 128/203.26, 128/203.27, 128/204.13, 128/204.17, 222/330, 126/263
• US Class Current: 128/203.27
• CPC Class Codes: A24F 42/60 Constructional details
• CPC Class Codes: A61M 11/041 using heaters
• CPC Class Codes: A61M 11/047 by exothermic chemical reaction
• CPC Class Codes: A61M 11/048 with a flame, e.g. using a burner
• CPC Class Codes: A61M 15/0031 by bursting or breaking the package, i.e. without cutting or piercing
• CPC Class Codes: A61M 15/0045 using multiple prepacked dosages on a same carrier, e.g. blisters
• CPC Class Codes: A61M 15/0051 the dosages being arranged on a tape, e.g. strips
• CPC Class Codes: A61M 15/06 Inhaling appliances shaped like cigars, cigarettes or pipes
• CPC Class Codes: A61M 2202/064 Powder
• CPC Class Codes: A61M 2205/364 by chemical reaction
• CPC Class Codes: A61M 2205/8268 Fuel storage cells

Abstract

Aerosol drug delivery devices incorporating percussively activated heat packages are disclosed. The heat packages include a percussive igniter and a fuel capable of undergoing an exothermic oxidation-reduction reaction when ignited by the percussive igniter. The drug delivery devices disclosed can be activated by an actuation mechanism to vaporize a thin solid film comprising a drug disposed on the exterior of a hat package. Metal coordination complexes of volatile drugs, and in particular nicotine, from which the drug can be selectively vaporized when heated are also disclosed. The use of aerosol drug delivery devices comprising thin films of nicotine metal salt complexes for the treatment of nicotine craving and for effecting smoking cessation are also disclosed.

Claims

1. A drug delivery device comprising:

a housing defining an airway, wherein the airway comprises at least one air inlet and a mouthpiece having at least one air outlet;

at least one percussively activated heat package disposed within the airway;

at least one drug disposed on the at least one percussively activated heat package; and

a mechanism configured to impact the at least one percussively activated heat package.

2. The drug delivery device of claim 1, wherein the percussively activated heat package comprises:

an enclosure comprising a region capable of being deformed by a mechanical impact;

an anvil disposed within the enclosure;

a percussive initiator composition disposed within the enclosure, wherein the initiator composition is configured to be ignited when the deformable region of the enclosure is deformed; and

a fuel disposed within the enclosure configured to be ignited by the initiator composition.

3. The drug delivery device of claim 1, wherein the drug is disposed on a surface of the heat package as a thin film.

4. The drug delivery device of claim 3, wherein the thickness of the thin film ranges from 0.01 μ

m to 20 μ

m.

5. The drug delivery device of claim 3, wherein the thickness of the thin film ranges from 0.5 μ

m to 10 μ

m.

6. The drug delivery device of claim 3, wherein the thin film comprises a metal coordination complex of a drug.

7. The drug delivery device of claim 6, wherein the metal coordination complex comprises at least one metal salt and at least one drug.

8. The drug delivery device of claim 7, wherein the at least one metal salt is selected from a salt of Zn, Cu, Fe, Co, Ni, Al, and mixtures thereof.

9. The drug delivery device of claim 6, wherein the thin film comprises a metal coordination complex of zinc bromide and nicotine.

10. The drug delivery device of claim 9, wherein the ratio of zinc bromide to nicotine is about 1:

2.

11. The drug delivery device of claim 6, wherein the metal coordination complex is soluble in at least one organic solvent.

12. The drug delivery device of claim 6, wherein the drug is selectively vaporizable from the metal coordination complex when the metal coordination complex comprising the drug is heated to a temperature ranging from 100°

C. to 500°

C.

13. The drug delivery device of claim 1, wherein the drug is vaporized when heated to a temperature of at least 250°

C.

14. The drug delivery device of claim 1, wherein the drug is selected from at least one of the following:

albuterol, alprazolam, apomorphine HCl, aripiprazole, atropine, azatadine, benztropine, bromazepam, brompheniramine, budesonide, bumetanide, buprenorphine, butorphanol, carbinoxamine, chlordiazepoxide, chlorpheniramine, ciclesonide, clemastine, clonidine, colchicine, cyproheptadine, diazepam, donepezil, eletriptan, estazolam, estradiol, fentanyl, flumazenil, flunisolide, flunitrazepam, fluphenazine, fluticasone propionate, frovatriptan, galanthamine, granisetron, hydromorphone, hyoscyamine, ibutilide, ketotifen, loperamide, melatonin, metaproterenol, methadone, midazolam, naratriptan, nicotine, oxybutynin, oxycodone, oxymorphone, pergolide, perphenazine, pindolol, pramipexole, prochlorperazine, rizatriptan, ropinirole, scopolamine, selegiline, tadalafil, terbutaline, testosterone, tetrahydrocannabinol, tolterodine, triamcinolone acetonide, triazolam, trifluoperazine, tropisetron, zaleplon, zolmitriptan, and zolpidem.

15. The drug delivery device of claim 1, wherein the drug is selected from the group consisting of nicotine, pramipexole, and a respiratory steroid.

16. The drug delivery device of claim 15, wherein the respiratory steroid is selected from budesonide, ciclesonide, fluisolide, fluticasone propionate, and triamcinolone acetonide.

17. The drug delivery device of claim 1, wherein the mechanism configured to impact is actuated mechanically, electrically, or by inhalation.

18. The drug delivery device of claim 17, wherein the electrical mechanism to impact comprises:

an airflow sensitive actuator coupled to the airway;

a mechanism coupled to the airflow sensitive actuator configured to activate the heat package; and

wherein the heat package is activated by an airflow in the airway produced by inhaling through the mouthpiece.

19. The drug delivery device of claim 17, wherein an inhalation mechanism configured to impact comprises:

a pressure sensitive diaphragm coupled to the airway;

a pre-stressed spring disposed within the housing configured to impact the percussively activated heat package when released; and

a lever rotatably coupled to the diaphragm and the housing, which upon rotation, releases the spring to impact the percussively activated heat package,

wherein the heat package is activated by an airflow in the airway produced by inhaling through the mouthpiece.

20. The drug delivery device of claim 17, wherein a mechanically actuated mechanism configured to impact comprises:

a manually operated switch;

a pre-stressed spring configured to impact the percussively activated heat package; and

a lever coupled to the switch, which upon actuation, releases the spring to impact the percussively activated heating element.

21. The drug delivery device of claim 17, wherein a mechanically actuated mechanism configured to impact comprises:

a manually operated switch;

a mass configured to impact the percussively activated heat package;

a pre-stressed spring configured to propel the mass;

a lever coupled to the switch, which upon actuation, releases the spring, propelling the mass to impact the percussively activated heat package.

22. The drug delivery device of claim 21, wherein the at least one drug is selected from nicotine, pramipexole, budesonide, cicliesonide, flunisolide, flutuicasone propionate, and triamcinolone acetonide.

23. The drug delivery device of claim 17, wherein the mechanically actuated mechanism configured to impact comprises a mass configured to impact the percussively activated heat package.

24. The drug delivery device of claim 17, wherein the mechanically actuated mechanism configured to impact comprises a rotatable sleeve that stresses and releases a spring when rotated.

25. The drug delivery device of claim 1, wherein an aerosol comprising the drug is formed in the airway when the heat package is activated.

26. The drug delivery device of claim 25, wherein the vapor purity of the drug forming the aerosol is at least 95%.

27. The drug delivery device of claim 1, wherein an air flow through the airway ranges from 10 L/min to 200 L/min.

28. The drug delivery device of claim 1, wherein the device comprises a plurality of percussively activated heat packages.

29. The drug delivery device of claim 28, wherein each of the plurality of heat packages is disposed within a recess.

30. The drug delivery device of claim 29, wherein the device further comprises a mechanism configured to advance actuation to an unactivated heat package.

31. A drug delivery device comprising:

a housing defining an airway, wherein the airway comprises at least one air inlet and a mouthpiece having at least one air outlet;

two or more percussively activated heat packages disposed within the airway;

at least one drug disposed on the percussively activated heat packages;

a mechanical mechanism configured to advance actuation to an unactivated heat package; and

a mechanically actuated mechanism configured to impact the at least one percussively activated heat package.

32. The device of claim 31, wherein the air outlet has a cross sectional area between about 0.01 in² to 1.5 in².

33. The device of claim 32, wherein an air flow through the airway ranges from 10 L/min to 200 L/min.

34. The device of claim 31, wherein the device comprises at least five percussively activated heat packages.

35. The device of claim 34, wherein the device comprises at least ten percussively activated heat packages.

36. The drug delivery device of claim 31, wherein each heat package is disposed within a recess.

37. The drug delivery device of claim 31, wherein the mechanically actuated mechanism configured to impact comprises:

a manually operated switch;

a pre-stressed spring configured to impact the percussively activated heat package; and

a lever coupled to the switch, which upon actuation, releases the spring to impact the percussively activated heating element.

38. The drug delivery device of claim 31, wherein the mechanically actuated mechanism configured to impact comprises:

a manually operated switch;

a mass configured to impact the percussively activated heat package;

a pre-stressed spring configured to propel the mass;

a lever coupled to the switch, which upon actuation, releases the spring, propelling the mass to impact the percussively activated heat package.

39. The drug delivery device of claim 31, wherein the mechanically actuated mechanism configured to impact comprises a mass configured to impact the percussively activated heat package.

40. The drug delivery device of claim 31, wherein the mechanically actuated mechanism configured to impact comprises a rotatable sleeve that stresses and releases a spring when rotated.

41. The drug delivery device of claim 31, wherein the drug disposed on the percussively activated heat packages is disposed as a thin film.

42. The drug delivery device of claim 41, wherein the thin film comprises a metal coordination complex of a drug.

43. The drug delivery device of claim 42, wherein the metal coordination complex comprises at least one metal salt and at least one drug.

44. The drug delivery device of claim 43, wherein the at least one metal salt is selected from a salt of Zn, Cu, Fe, Co, Ni, Al, and mixtures thereof.

45. The drug delivery device of claim 41, wherein the thin film comprises a metal coordination complex of zinc bromide and nicotine.

46. The drug delivery device of claim 45, wherein the ratio of zinc bromide to nicotine is about 1:

2.

47. The drug delivery device of claim 31, wherein the at least one drug is selected from at least one of the following:

albuterol, alprazolam, apomorphine HCl, aripiprazole, atropine, azatadine, benztropine, bromazepam, brompheniramine, budesonide, bumetanide, buprenorphine, butorphanol, carbinoxamine, chlordiazepoxide, chlorpheniramine, ciclesonide, clemastine, clonidine, colchicine, cyproheptadine, diazepam, donepezil, eletriptan, estazolam, estradiol, fentanyl, flumazenil, flunisolide, flunitrazepam, fluphenazine, fluticasone propionate, frovatriptan, galanthamine, granisetron, hydromorphone, hyoscyamine, ibutilide, ketotifen, loperamide, melatonin, metaproterenol, methadone, midazolam, naratriptan, nicotine, oxybutynin, oxycodone, oxymorphone, pergolide, perphenazine, pindolol, pramipexole, prochlorperazine, rizatriptan, ropinirole, scopolamine, selegiline, tadalafil, terbutaline, testosterone, tetrahydrocannabinol, tolterodine, triamcinolone acetonide, triazolam, trifluoperazine, tropisetron, zaleplon, zolmitriptan, and zolpidem.

48. The drug delivery device of claim 31, wherein the at least one drug is selected from the group consisting of nicotine, pramipexole, and a respiratory steroid.

49. The drug delivery device of claim 48, wherein the respiratory steroid is selected from budesonide, ciclesonide, fluisolide, fluticasone propionate, and triamcinolone acetonide.

50. The drug delivery device of claim 31, wherein the at least one drug is selected from nicotine, pramipexole, budesonide, cicliesonide, flunisolide, flutuicasone propionate, and triamcinolone acetonide.

51. A method of delivering a drug to a patient comprising:

providing a drug delivery device comprising;

a housing defining an airway, wherein the airway comprises at least one air inlet and a mouthpiece having at least one air outlet;

at least two or more percussively activated heat package disposed within the airway;

at least one drug disposed on the at least two or more percussively activated heat package; and

a mechanism configured to impact the percussively activated heat packages;

inhaling through the mouthpiece; and

actuating the mechanism configured to impact;

wherein the percussively activated heat package vaporizes the at least one drug to form an aerosol comprising the drug in the airway which is inhaled by the patient.

52. A drug aerosol delivery device comprising:

a housing defining an airway, wherein the airway comprises at least one air inlet and a mouthpiece comprising at least one air outlet;

a plurality of percussively activated heat packages configured to be disposed within the airway;

a thin film comprising at least one drug disposed on each of the percussively activated heat packages; and

a manually operated switch coupled to at least one spring configured to impact at least one percussively activated heat package disposed within the airway,

wherein when actuated, the drug is vaporized to form an aerosol comprising the drug in the airway.