Treatment of breakthrough pain by drug aerosol inhalation

• US 20050126562A1
• Filed: 11/23/2004
• Published: 06/16/2005
• Est. Priority Date: 12/15/2003
• Status: Abandoned Application

• Current Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Original Assignee: Alexza Molecular Delivery Corporation (Grupo Ferrer Internacional SA)
• Inventors: Rabinowitz, Joshua D., Wensley, Martin J., Shen, William W.
• Application Number:
  US10/996,162
• Publication Number:
  US 20050126562A1
• Time in Patent Office: Days
• US Class Current: 128/200.230
• CPC Class Codes: A61J 7/0445 for preventing drug dispensing during a predetermined time period
• CPC Class Codes: A61M 11/041 using heaters
• CPC Class Codes: A61M 11/042 electrical
• CPC Class Codes: A61M 15/00 Inhalators drug delivery in endotracheal tubes A61M16/04
• CPC Class Codes: A61M 15/0003 with means for dispensing more than one drug
• 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 2016/0021 with a proportional output signal, e.g. from a thermistor
• CPC Class Codes: A61M 2202/064 Powder
• CPC Class Codes: A61M 2205/60 with identification means
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids

Abstract

Devices comprising a housing defining an airway, at least one support configured to couple to the airway comprising at least one area selected from a first area and a second area, wherein a first compound is disposed on the first area, and a second compound is disposed on the second area, and wherein the second compound can counteract the pharmacological effects of the first compound; and a mechanism configured to release the first compound into the airway, wherein the device comprises at least one first area and at least one second area are disclosed. Methods of producing an aerosol of a first compound comprising providing at least one first area on which is disposed a first compound, and at least one second area on which is disposed a second compound, providing an airflow over at least a portion of the at least one first area, and releasing the first compound from at least a portion of at least one first area into the airflow, wherein the first compound forms an aerosol in the airflow, are also disclosed. Methods of using the devices and the methods of producing an aerosol are also disclosed.

Claims

1. A device comprising:

a housing defining an airway;

at least one support configured to couple to the airway comprising at least one area selected from a first area and a second area, wherein a first compound is disposed on the first area, and a second compound is disposed on the second area, and wherein the second compound can counteract the pharmacological effects of the first compound; and

a mechanism configured to release the first compound into the airway coupled to the support;

wherein the device comprises at least one first area and at least one second area.

2. The device of claim 1, wherein the mechanism to release does not release the second compound into the airway.

3. The device of claim 1, wherein an aerosol comprising the first compound is formed when the first compound is released into the airway.

4. The device of claim 1, wherein the device comprises more than one airway.

5. The device of claim 1, wherein the support comprises more than one support.

6. The device of claim 1, wherein the support comprises more than one first area.

7. The device of claim 1 wherein the support comprises more than one second area.

8. The device of claim 1, wherein the support comprises more than one first area and more than one second area.

9. The device of claim 8, wherein the more than one first areas are spatially interspersed among the more than one second areas.

10. The device of claim 1, wherein the at least one first area and the at least one second area are disposed on different supports.

11. The device of claim 1, wherein the at least one first area and the at least one second area are disposed on the same support.

12. The device of claim 1, wherein the first compound disposed on the first area and the second compound disposed on the second area are indistinguishable to visual observation.

13. The device of claim 1, wherein the at least one first area and the at least one second area are positionally distinguishable.

14. The device of claim 1, wherein the mechanism configured to release releases the first compound from a single first area into the airway.

15. The device of claim 1, wherein the mechanism configured to release releases the first compound from more than one first area into the airway.

16. The device of claim 1, wherein the mechanism configured to release is selected from a thermal mechanism, a mechanical mechanism, and an acoustic mechanism.

17. The device of claim 16, wherein the thermal mechanism heats the first area from ambient temperature to a temperature ranging from 200°

C. to 600°

C. within 500 msec.

18. The device of claim 16, wherein the thermal mechanism is selected from resistive heating, optical heating, and chemical heating.

19. The device of claim 1, further comprising a power source and a controller.

20. The device of claim 19, wherein the controller controls the time interval between subsequent actuations of the mechanism configured to release.

21. The device of claim 19, wherein the controller controls the amount of first compound released by the mechanism configured to release.

22. The device of claim 19, wherein the controller is adjustable by a patient.

23. The device of claim 1, further comprising an actuation mechanism.

24. The device of claim 1, further comprising a lock-out mechanism.

25. A device comprising:

a housing defining an airway;

a support configured to couple to the airway comprising at least one first area and at least one second area, wherein a first compound is disposed on the at least one first area, and a second compound is disposed on the at least one second area, and wherein the second compound can counteract the pharmacological effects of the first compound; and

a mechanism configured to release the first compound disposed on the at least one first area into the airway.

26. The device of claim 25, wherein the support comprises more than one first area.

27. The device of claim 25, wherein the support comprises more than one second area.

28. A device comprising:

a housing defining an airway;

more than one support configured to couple to the airway comprising at least one first area and at least one second area, wherein a first compound is disposed on the at least one first area, and a second compound is disposed on the at least one second area, and wherein the second compound can counteract the pharmacological effects of the first compound; and

a mechanism configured to release the first compound disposed on the at least one first area into the airway.

29. The device of claim 28, wherein the more than one support comprises more than one first area and more than one second area.

30. A device comprising:

a housing defining an airway;

a first support configured to couple to the airway comprising at least one first area, wherein a first compound is disposed on the at least one first area;

a second support comprising at least one second area, wherein a second compound is disposed on the at least one second area, and wherein the second compound can counteract the pharmacological effects of the first compound; and

a mechanism configured to release the first compound into the airway.

31. The device of claim 30, wherein the first support comprises more than one first area.

32. The device of claim 30, wherein the second support comprises more than one second area.

33. A device comprising:

a housing defining an airway;

more than one first support configured to couple to the airway comprising at least one first area, wherein a first compound is disposed on the at least one first area;

more than one second support comprising at least one second area, wherein a second compound is disposed on the at least one second area, and wherein the second compound can counteract the pharmacological effects of the first compound; and

a mechanism configured to release the first compound into the airway.

34. The device of claim 33, wherein the first support comprises more than one first area.

35. The device of claim 33, wherein the second support comprises more than one second area.

36. A device comprising:

a housing defining an airway;

a support configured to couple to the airway comprising more than one first areas and a second area, wherein a first compound is disposed on the more than one first areas, and a second compound is disposed on the second area, and wherein the second compound can counteract the pharmacological effects of the first compound; and

a mechanism configured to thermally vaporize the first compound disposed on at least one of the first areas into the airway.

37. The device of claim 36, wherein an aerosol comprising the first compound is formed when the first compound is thermally vaporized into the airway.

38. The device of claim 37, wherein the aerosol does not comprise the second compound.

39. The device of claim 37, wherein the aerosol comprises a therapeutically effective amount of the first compound.

40. The device of claim 37, wherein the aerosol exhibits an average mass median aerodynamic diameter ranging from 1 μ

m to 3 μ

m.

41. The device of claim 40, wherein the aerosol exhibits a geometric standard deviation of the log-normal particle size distribution of less than 3.

42. The device of claim 36, wherein at least a portion of at least one of the first areas is disposed within the airway.

43. The device of claim 36, wherein the support is thermally conductive.

44. The device of claim 36, wherein the support comprises stainless steel.

45. The device of claim 36, wherein the support comprises multiple layers.

46. The device of claim 36, wherein the support comprises at least one of a metal foil, a metal plate, a metal shell, and a metal disk.

47. The device of claim 36, wherein the first area comprises a thermally conductive material.

48. The device of claim 36, wherein the first compound comprises a pharmaceutical compound.

49. The device of claim 36, wherein the first compound comprises an opioid analgesic.

50. The device of claim 49, wherein the opioid analgesic compound is selected from at least one of the following:

fentanyl, sufentanyl, remifentanyl, morphine, hydromorphone, oxymorphone, codeine, hydrocodone, oxycodone, meperidine, methadone, nalbuphine, buprenorphine, and buorphanol.

51. The device of claim 36, wherein the second compound comprises an antagonist of an opioid analgesic.

52. The device of claim 36, wherein the first compound comprises at least fentanyl and the second compound comprises at least one fentanyl antagonist compound.

53. The device of claim 52, wherein the at least one fentanyl antagonist compound is selected from naloxone and naltrexone.

54. The device of claim 36, wherein the first compound comprises a thin film.

55. The device of claim 54, wherein the thickness of the thin film is less than 20 μ

m.

56. The device of claim 36, wherein the first compound comprises an abusable substance.

57. The device of claim 36, wherein the first area exhibits properties that facilitate release of the first compound.

58. The device of claim 57, wherein the properties are selected from at least one of the following:

thermal properties, optical properties, electrical properties, physical properties, and mechanical properties.

59. The device of claim 36, wherein the second area exhibits properties that inhibit release of the second compound under conditions in which the first compound is released.

60. The device of claim 59, wherein the properties are selected from at least one of the following:

thermal properties, optical properties, electrical properties, physical properties, and mechanical properties.

61. The device of claim 36, wherein less than 5% of the first compound is degraded during thermal vaporization.

62. The device of claim 36, further comprising a power source and a controller.

63. The device of claim 62, wherein the controller controls the time interval between subsequent actuations of the mechanism configured to release.

64. The device of claim 62, wherein the controller controls the amount of first compound released by the mechanism configured to release.

65. The device of claim 62, wherein the amount of first compound released in a single actuation of the device is adjustable by a patient.

66. The device of claim 36, further comprising an actuation mechanism.

67. The device of claim 66, wherein the actuation mechanism comprises an airflow sensor.

68. The device of claim 67, wherein the actuation mechanism is activated when the velocity of the airflow through the airway exceeds a pre-established threshold.

69. The device of claim 68, wherein the pre-established threshold is at least 1 m/sec.

70. The device of claim 36, further comprising a lock-out mechanism.

71. The device of claim 70, wherein the lock-out mechanism controls the time interval between successive actuations of the mechanism configured to thermally vaporize.

72. The device of claim 36, wherein the mechanism configured to thermally vaporize is selected from resistive heating, optical heating, and chemical heating.

73. The device of claim 36, wherein an airflow is generated through the airway upon inhalation by a patient.

74. The device of claim 36, further comprising at least one airflow control valve operatively connected to the airway.

75. The device of claim 74, wherein the at least one airflow control valve is configured to maintain the airflow rate through the airway to range from 10 L/min to 120 L/min.

76. The device of claim 36, further comprising a mechanism configured to move the support.

77. A method of producing an aerosol of a first compound comprising:

providing at least one first area on which is disposed a first compound, and at least one second area on which is disposed a second compound, wherein the second compound can counteract the pharmacological effects of the first compound;

providing an airflow over at least a portion of the least one first area; and

releasing the first compound from at least a portion of the at least one first area into the airflow;

wherein the first compound forms an aerosol in the airflow.

78. A method of administering a therapeutically effective amount of a first compound to a patient comprising inhaling an aerosol produced by a device comprising:

a housing defining an airway;

at least one support configured to couple to the airway comprising at least one area selected from a first area and a second area, wherein a first compound is disposed on the first area, and a second compound is disposed on the second area, and wherein the second compound can counteract the pharmacological effects of the first compound; and

a mechanism configured to release at least a portion of the first compound into the airway;

wherein the device comprises at least one first area and at least one second area.

79. A method of administering a therapeutically effective amount of at least one first compound to a patient comprising inhaling an aerosol produced using the method comprising:

providing at least one first area on which is disposed a first compound, and at least one second area on which is disposed a second compound, wherein the second compound can counteract the pharmacological effects of the first compound;

providing an airflow over at least a portion of the least one first area; and

releasing the first compound from at least a portion of the at least one first area into the airflow;

wherein the first compound forms an aerosol in the airflow.

80. 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 at least one first compound, wherein the aerosol is produced by a device comprising:

a housing defining an airway;

at least one support configured to couple to the airway comprising at least one area selected from a first area and a second area, wherein a first compound is disposed on the first area, and a second compound is disposed on the second area, wherein the second compound can counteract the pharmacological effects of the first compound; and

a mechanism configured to release the first compound into the airway;

wherein the device comprises at least one first area and at least one second area.

81. 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 at least one first compound, wherein the aerosol is produced by the method comprising:

providing at least one first area on which is disposed a first compound, and at least one second area on which is disposed a second compound, wherein the second compound can counteract the pharmacological effects of the first compound;

providing an airflow over at least a portion of the least one first area; and

releasing the first compound from at least a portion of the at least one first area into the airflow;

wherein the first compound forms an aerosol in the airflow.

82. An aerosol produced using a device comprising:

a housing defining an airway;

at least one support configured to couple to the airway comprising at least one area selected from a first area and a second area, wherein a first compound is disposed on the first area, and a second compound is disposed on the second area, wherein the second compound can counteract the pharmacological effects of the first compound; and

a mechanism configured to release the first compound into the airway;

wherein the device comprises at least one first area and at least one second area.

83. An aerosol produced by the method of:

providing at least one first area on which is disposed a first compound, and at least one second area on which is disposed a second compound, wherein the second compound can counteract the pharmacological effects of the first compound;

providing an airflow over at least a portion of the least one first area; and

releasing the first compound from at least a portion of the at least one first area into the airflow;

wherein the first compound forms an aerosol in the airflow.