Self-contained heating unit and drug-supply unit employing same

• US 20050079166A1
• Filed: 05/20/2004
• Published: 04/14/2005
• Est. Priority Date: 05/21/2003
• Status: Abandoned Application

• Current Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Original Assignee: Alexza Molecular Delivery Corporation (Grupo Ferrer Internacional SA)
• Inventors: Tom, Curtis, Hale, Ron L., Quintana, Reynaldo J., Myers, Daniel J., Solas, Dennis W., Song, Soonho, Soni, Pravin, Damani, Ramesh
• Application Number:
  US10/850,895
• Publication Number:
  US 20050079166A1
• Time in Patent Office: Days
• US Class Current: 424/122
• CPC Class Codes: A61M 11/00 Sprayers or atomisers specially adapted for therapeutic purposes in general B05B; aerosol containers B65D83/14
• 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 11/048 with a flame, e.g. using a burner
• CPC Class Codes: A61M 15/06 Inhaling appliances shaped like cigars, cigarettes or pipes
• CPC Class Codes: A61M 2016/0021 with a proportional output signal, e.g. from a thermistor
• CPC Class Codes: A61M 2016/0027 pressure meter
• CPC Class Codes: A61M 2202/064 Powder
• CPC Class Codes: A61M 2205/36 related to heating or cooling
• CPC Class Codes: A61M 2205/364 by chemical reaction
• CPC Class Codes: A61M 2205/3653 by Joule effect, i.e. electric resistance
• CPC Class Codes: A61M 2205/8268 Fuel storage cells
• CPC Class Codes: B01B 1/005 Evaporation for physical or chemical purposes; Evaporation apparatus therefor, e.g. evaporation of liquids for gas phase reactions
• CPC Class Codes: B65B 29/10 Packaging two or more different substances isolated from one another in the package but capable of being mixed without opening the package, e.g. forming packages containing a resin and hardener isolated by a frangible partition
• CPC Class Codes: C06B 33/00 Compositions containing particulate metal, alloy, boron, silicon, selenium or tellurium with at least one oxygen supplying material which is either a metal oxide or a salt, organic or inorganic, capable of yielding a metal oxide
• CPC Class Codes: C06B 45/14 a layer or zone containing an inorganic explosive or an inorganic explosive or an inorganic thermic component
• CPC Class Codes: C09K 5/18 Non-reversible chemical reactions
• CPC Class Codes: F23B 2900/00003 Combustion devices specially adapted for burning metal fuels, e.g. Al or Mg
• CPC Class Codes: F23C 2900/99008 Unmixed combustion, i.e. without direct mixing of oxygen gas and fuel, but using the oxygen from a metal oxide, e.g. FeO
• CPC Class Codes: F24V 30/00 : Apparatus or devices using heat produced by exothermal chemical reactions other than combustion
• CPC Class Codes: Y02E 20/34 : Indirect CO2mitigation, i.e. by acting on non CO2directly related matters of the process, e.g. pre-heating or heat recovery

Abstract

Heating units, drug supply units and drug delivery articles capable of rapid heating are disclosed. Heating units comprising a substrate and a solid fuel capable of undergoing an exothermic metal oxidation reaction disposed within the substrate are disclosed. Drug supply units and drug delivery articles wherein a solid fuel is configured to heat a substrate to a temperature sufficient to rapidly thermally vaporize a drug disposed thereon are also disclosed.

Claims

1. A heating unit comprising:

an enclosure; and

a solid fuel capable of undergoing an exothermic metal oxidation-reduction reaction disposed within the enclosure.

2. A heating unit comprising:

an enclosure; and

a solid fuel comprising a metal reducing agent and a metal-containing oxidizing agent disposed within the enclosure.

3. A heating unit comprising:

an enclosure comprising at least one substrate having an exterior surface and an interior surface; and

a solid fuel disposed within the enclosure;

wherein the solid fuel is configured to heat a portion of the exterior surface of the at least one substrate to a temperature of at least 200°

C. within at least 3 seconds following ignition of the solid fuel.

4. The drug supply unit of claim 3, wherein the solid fuel is configured to heat a portion of the exterior surface of the at least one substrate to a temperature of at least 200°

C. within at least 500 milliseconds following ignition of the solid fuel.

5. The drug supply unit of claim 3, wherein the solid fuel is configured to heat a portion of the exterior surface of the at least one substrate to a temperature of at least 200°

C. within at least 250 milliseconds following ignition of the solid fuel.

6. A heating unit comprising:

a sealed enclosure comprising at least one substrate having an exterior surface and an interior surface;

a solid fuel comprising a metal reducing agent and a metal-containing oxidizing agent disposed on a portion of the interior surface of the substrate; and

an impulse absorbing material disposed within the enclosure;

wherein the solid fuel is configured to heat a portion of the exterior surface of the at least one substrate to a temperature of at least 200°

C. within at least 500 milliseconds following ignition of the solid fuel.

7. The heating unit of claim 6, wherein the substrate is selected from a metal, an alloy, and a ceramic.

8. The heating unit of claim 6, wherein the enclosure comprises more than one substrate.

9. The heating unit of claim 6, wherein the substrate is a metal foil.

10. The heating unit of claim 9, wherein the metal foil exhibits a thickness ranging from 0.001 inches to 0.010 inches.

11. The heating unit of claim 6, wherein the sealed enclosure is capable of withstanding an internal pressure of at least 50 psig.

12. The heating unit of claim 6, wherein the sealed enclosure is capable of withstanding an internal pressure of at least 20 psig.

13. The heating unit of claim 6, wherein the metal reducing agent is selected from at least one of the following:

aluminum, zirconium, and titanium.

14. The heating unit of claim 6, wherein the metal-containing oxidizing agent is selected from at least one of the following:

MoO₃, KClO₄, KClO₃ and Fe₂O₃.

15. The heating unit of claim 6, wherein the solid fuel is selected from a composition comprising Zr and MoO₃, and Zr and Fe₂O₃.

16. The heating unit of claim 6, wherein the solid fuel is selected from a composition comprising Al and MoO₃, and Al and Fe₂O₃.

17. The heating unit of claim 6, wherein the amount of metal reducing agent ranges from 60% by weight to 90% by weight of the total dry weight of the solid fuel.

18. The heating unit of claim 6, wherein the amount of metal-containing oxidizing agent ranges from 10% by weight to 40% by weight of the total dry weight of the solid fuel.

19. The heating unit of claim 6, wherein the solid fuel comprises at least one additive material.

20. The heating unit of claim 19, wherein the additive material comprises a binder selected from at least one of the following:

nitrocellulose and polyvinylalcohol.

21. The heating unit of claim 19, wherein the additive material is selected from at least one of the following:

diatomaceous earth, glass beads, and colloidal silica.

22. The heating unit of claim 19, wherein the additive material comprises Laponite®

RDS.

23. The heating unit of claim 6, wherein the metal reducing agent and the metal-containing oxidizing agent comprise powders.

24. The heating unit of claim 23, wherein the powders exhibit a particle size ranging from 100 mesh to 350 mesh.

25. The heating unit of claim 23, wherein the powders exhibit a particle size ranging from 0.1 μ

m to 200 μ

m.

26. The heating unit of claim 6, wherein the solid fuel comprises more than one metal reducing agent.

27. The heating unit of claim 6, wherein the solid fuel comprises more than one metal-containing oxidizing agent.

28. The heating unit of claim 6, wherein the solid fuel is in the form of a thin layer exhibiting a thickness ranging from 0.001 inches to 0.030 inches.

29. The heating unit of claim 6, wherein the solid fuel is in the form of a thin layer exhibiting a thickness ranging from 0.001 inches to 0.005 inches.

30. The heating unit of claim 6, wherein the mass of the solid fuel ranges from 0.01 grams to 1.0 grams.

31. The heating unit of claim 6, wherein the solid fuel adjoins the interior surface of the substrate.

32. The heating unit of claim 6, further comprising a thermal shunt within the enclosure.

33. The heating unit of claim 6, further comprising at least one impulse absorbing material.

34. The heating unit of claim 33, wherein the impulse absorbing material is selected from a porous material, and a fibrous material.

35. The heating unit of claim 6, further comprising at least one getter.

36. The heating unit of claim 6, further comprising at least one igniter.

37. The heating unit of claim 36, wherein the igniter is disposed within the enclosure.

38. The heating unit of claim 36, wherein the igniter comprises a resistive heating element and an initiator composition disposed on the resistive heating element.

39. The heating unit of claim 38, wherein the initiator composition comprises at least one reducing agent and at least one oxidizing agent.

40. The heating unit of claim 39, wherein the reducing agent of the initiator composition is selected from at least one of the following:

aluminum, zirconium, and boron.

41. The heating unit of claim 39, wherein the oxidizing agent of the initiator composition is selected from at least one of the following:

a chlorate of an alkali metal, a chlorate of an alkali earth metal, a perchlorate of an alkali metal, and a perchlorate of an alkali earth metal.

42. The heating unit of claim 39, wherein the oxidizing agent is selected from at least one of the following:

potassium chlorate, and potassium perchlorate.

43. The heating unit of claim 38, wherein the initiator composition comprises at least one additive material.

44. The heating unit of claim 43, wherein the additive material is selected from at least one of the following:

diatomaceous earth, glass beads, and colloidal silica.

45. The heating unit of claim 6, wherein a portion of the external surface of the substrate reaches a temperature of at least 200°

C. within less than 250 milliseconds following ignition of the solid fuel.

46. The heating unit of claim 6, wherein the solid fuel has a burn front with a propagation speed that ranges from 1.5 cm/sec to 50 cm/sec.

47. A drug supply unit comprising:

an enclosure comprising at least one substrate having an exterior surface and an interior surface;

a solid fuel capable of undergoing an exothermic metal oxidation-reduction reaction disposed within the enclosure; and

a drug disposed on a portion of the exterior surface of the substrate.

48. A drug supply unit comprising:

an enclosure comprising at least one substrate having an exterior surface and an interior surface;

a solid fuel comprising a metal reducing agent and a metal-containing oxidizing agent disposed within the enclosure; and

a drug disposed on a portion of the exterior surface of the substrate.

49. A drug supply unit comprising:

an enclosure comprising at least one substrate having an exterior surface and an interior surface; and

a solid fuel disposed within the enclosure, and;

a drug disposed on a portion of the exterior surface of the substrate;

wherein the solid fuel is configured to heat a portion of the exterior surface of the at least one substrate to a temperature sufficient to thermally vaporize the drug within at least 1000 milliseconds following ignition of the solid fuel.

50. The drug supply unit of claim 49, wherein the temperature is at least 200°

C.

51. The drug supply unit of claim 49, wherein the solid fuel is configured to heat a portion of the exterior surface of the at least one substrate to a temperature sufficient to thermally vaporize the drug within at least 800 milliseconds following ignition of the solid fuel.

52. The drug supply unit of claim 49, wherein the solid fuel is configured to heat a portion of the exterior surface of the at least one substrate to a temperature sufficient to thermally vaporize the drug within at least 500 milliseconds following ignition of the solid fuel.

53. The drug supply unit of claim 49, wherein the solid fuel is configured to heat a portion of the exterior surface of the at least one substrate to a temperature sufficient to thermally vaporize the drug within at least 250 milliseconds following ignition of the solid fuel.

54. A drug supply unit comprising:

a sealed enclosure comprising at least one substrate having an exterior surface and an interior surface;

a solid fuel comprising a metal reducing agent and a metal-containing oxidizing agent disposed on a portion of the interior surface of the substrate an impulse absorbing material disposed within the enclosure; and

a drug disposed on a portion of the exterior surface of the substrate;

wherein the solid fuel is configured to heat a portion of the exterior surface of the at least one substrate to a temperature sufficient to thermally vaporize the drug within at least 3 seconds following ignition of the solid fuel.

55. The drug supply unit of claim 54, wherein the drug comprises a pharmaceutically acceptable compound.

56. The drug supply unit of claim 54, wherein the drug comprises a therapeutically effective amount.

57. The drug supply unit of claim 54, wherein the drug comprises a film.

58. The drug supply unit of claim 54, wherein the film is less than 20 μ

m thick.

59. The drug supply unit of claim 54, wherein the drug is in the form of crystals.

60. The drug supply unit of claim 54, wherein the substrate comprise metal foil.

61. The drug supply unit of claim 60, wherein the metal foil comprises stainless steel.

62. The drug supply unit of claim 61, wherein the metal foil has a thickness of less than 0.010 inches.

63. The drug supply unit of claim 54, further comprising an igniter.

64. The drug supply unit of claim 63 wherein the igniter is disposed within the enclosure.

65. The drug supply unit of claim 64 further comprising a getter.

66. A drug supply unit comprising:

a plurality of heating units, each heating unit comprising;

an enclosure comprising at least one substrate having an exterior surface and an interior surface; and

a solid fuel capable of undergoing an exothermic metal oxidation-reduction reaction disposed within the enclosure; and

a drug disposed on a portion of the exterior surface of the at least one substrate forming each heating unit.

67. The drug supply unit of claim 66, wherein each heating unit further comprises an igniter disposed within the enclosure.

86. A method of treating a disease in a patient in need of such treatment comprising administering to the patient an aerosol comprising a therapeutically effective amount of a drug, wherein the aerosol is produced by a device according to any one of claims 66, 68, 69, 70, 75, or 80.

68. A drug delivery device comprising:

a housing defining an airway;

a heating unit comprising;

an enclosure comprising at least one substrate having an exterior surface and an interior surface; and

a solid fuel capable of undergoing an exothermic metal oxidation-reduction reaction disposed within the enclosure;

a drug disposed on a portion of the exterior surface of the substrate, wherein the portion of the exterior surface comprising the drug is configured to be disposed within the airway; and

an igniter configured to ignite the solid fuel.

69. A drug delivery device comprising:

a housing defining an airway;

a heating unit comprising;

an enclosure comprising at least one substrate comprising an exterior surface and an interior surface; and

a solid fuel comprising a metal reducing agent and a metal-containing oxidizing agent disposed within the enclosure;

a drug disposed on a portion of the exterior surface of the substrate, wherein the portion of the exterior surface comprising the drug is configured to be disposed within the airway;

an initiator composition configured to ignite the solid fuel.

70. A drug delivery device comprising:

a housing defining an airway;

a heating unit comprising;

an enclosure comprising at least one substrate having an exterior surface and an interior surface; and

a solid fuel disposed within the enclosure,

a drug disposed on a portion of the exterior surface of the substrate, wherein the portion of the exterior surface comprising the drug is configured to be disposed within the airway; and

an initiator composition configured to ignite the solid fuel;

wherein the solid fuel is configured to heat a portion of the exterior surface of the at least one substrate to a temperature sufficient to thermally vaporize the drug within at least 1000 milliseconds following ignition of the solid fuel.

71. The drug delivery device of claim 70, wherein the temperature is at least 200°

C.

72. The drug delivery device of claim 70, wherein the solid fuel is configured to heat a portion of the exterior surface of the at least one substrate to a temperature sufficient to thermally vaporize the drug within at least 800 milliseconds following ignition of the solid fuel.

73. The drug delivery device of claim 70, wherein the solid fuel is configured to heat a portion of the exterior surface of the at least one substrate to a temperature sufficient to thermally vaporize the drug within at least 500 milliseconds following ignition of the solid fuel.

74. The drug delivery device of claim 70, wherein the solid fuel is configured to heat a portion of the exterior surface of the at least one substrate to a temperature sufficient to thermally vaporize the drug within at least 250 milliseconds following ignition of the solid fuel.

75. A drug delivery device comprising:

a housing defining an airway;

a heating unit comprising;

a sealed enclosure comprising at least one substrate having an exterior surface and an interior surface;

a solid fuel comprising a metal and a metal-containing oxidizer disposed on a portion of the interior surface of the substrate; and

an impulse absorbing material disposed within the enclosure;

a drug disposed on a portion of the exterior surface of the substrate, the portion of the exterior surface comprising the drug configured to be disposed within the airway;

an igniter configured to ignite the solid fuel, wherein the igniter is disposed within the enclosure; and

a mechanism configured to activate the igniter;

wherein the solid fuel is configured to heat a portion of the exterior surface of the at least one substrate to a temperature sufficient to thermally vaporize the drug within at least 1000 milliseconds following ignition of the solid fuel.

76. The drug delivery device of claim 75, wherein the solid fuel is configured to burn in the direction of the airflow.

77. The drug delivery device of claim 75, wherein the solid fuel is configured to burn in the direction opposite the airflow.

78. The drug delivery device of claim 75, wherein the solid fuel is configured to burn in a direction normal to the airflow.

79. The drug delivery device of claim 75, wherein the mechanism configured to activate the igniter is selected from a mechanism for producing an electric current, a mechanism for producing electromagnetic radiation, and a mechanism for producing a percussive force.

80. A drug delivery device comprising:

a housing defining at least one airway;

a plurality of heating units, each unit comprising;

an enclosure comprising at least one substrate having an exterior surface and an interior surface; and

a solid fuel capable of undergoing an exothermic metal oxidation-reduction reaction disposed within the enclosure;

a drug disposed on a portion of the exterior surface of the at least one substrate of each heating unit, wherein the portion of the exterior surface comprising the drug is configured to be disposed within the at least one airway; and

an igniter configured to ignite the solid fuel.

81. The drug delivery device of claim 80, further comprising a mechanism to move the portion of the exterior surface of the substrate comprising the drug of each of the plurality heating units into the airway.

82. The drug delivery device of claim 80, further comprising a mechanism configured to activate the igniter.

83. A method of producing an aerosol of a drug comprising:

providing an airflow over the drug disposed on a portion of an exterior surface of a substrate forming a drug supply unit, wherein the drug supply unit comprises;

a heating unit comprising;

an enclosure comprising the substrate; and

a solid fuel capable of undergoing an exothermic metal oxidation-reduction reaction disposed within the enclosure;

the drug disposed on a portion of the exterior surface of the substrate, wherein the portion of the exterior surface comprising the drug is disposed within the airway; and

an igniter configured to ignite the solid chemical fuel; and

activating the igniter to thermally vaporize the drug;

wherein the aerosol comprising the drug is formed in the airflow.

84. A method of treating a disease in a patient in need of such treatment comprising administering to the patient an aerosol comprising a therapeutically effective amount of a drug, wherein the aerosol is produced by the method according to claim 83.

85. The method of claim 84, wherein administering is selected from inhalation, nasal ingestion, and topical application.