Systems and methods for aerosolizing pharmaceutical formulations

• US 6,606,992 B1
• Filed: 05/30/2000
• Issued: 08/19/2003
• Est. Priority Date: 06/30/1999
• Status: Expired due to Term

• Current Assignee: Novartis Pharma AG (Novartis Ag)
• Original Assignee: Nektar Therapeutics Incorporated
• Inventors: Nason, Kevin S., Alston, William W. Jr., Rasmussen, Dennis R., Bakshi, Aneesh, Tuttle, Derrick J., Ward, Brian R. S., Clark, Andrew, Smith, Adrian E., Schuler, Carlos, Paboojian, Steve
• Primary Examiner(s): Lo, Weilun
• Assistant Examiner(s): EREZO, DARWIN P
• Application Number:
  US09/583,312
• Time in Patent Office: 1,176 Days
• Field of Search: 128/203.15, 128/205.13, 128/203.12, 128/203.18, 128/203.21, 128/205.21, 128/203.23, 604/58
• US Class Current: 128/203.15
• 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 15/0036 hollow piercing means
• CPC Class Codes: A61M 15/0051 the dosages being arranged on a tape, e.g. strips
• CPC Class Codes: A61M 15/0068 Indicating or counting the number of dispensed doses or of remaining doses
• CPC Class Codes: A61M 15/0083 Timers
• CPC Class Codes: A61M 15/0091 mechanically breath-triggered
• CPC Class Codes: A61M 15/0093 without arming or cocking, e.g. acting directly on the delivery valve
• CPC Class Codes: A61M 15/0096 Hindering inhalation before activation of the dispenser
• CPC Class Codes: A61M 16/0493 with means for protecting the tube from damage caused by the patient's teeth, e.g. bite block
• CPC Class Codes: A61M 16/0495 with tongue depressors
• CPC Class Codes: A61M 16/0866 Passive resistors therefor
• CPC Class Codes: A61M 16/206 Capsule valves, e.g. mushroom, membrane valves
• CPC Class Codes: A61M 16/208 Non-controlled one-way valves, e.g. exhalation, check, pop-off non-rebreathing valves
• CPC Class Codes: A61M 2202/064 Powder

Abstract

Systems and methods are provided for aerosolizing a pharmaceutical formulation. According to one method, respiratory gases are prevented from flowing to the lungs when attempting to inhale. Then, respiratory gases are abruptly permitted to flow to the lungs. The flow of respiratory gases may then be used to extract a pharmaceutical formulation from a receptacle and to place the pharmaceutical formulation within the flow of respiratory gases to form an aerosol.

Claims

1. A method for aerosolizing a pharmaceutical formulation, the method comprising:

placing a valve within an airway leading to the lungs to prevent respiratory gases from flowing to the lungs when user attempts to inhale, and then abruptly permitting respiratory gases to flow to the lungs by opening the valve when a threshold actuating vacuum caused by the attempted inhalation is exceeded, wherein the threshold actuating vacuum is in a range from about 20 cm H₂O to about 60 cm H₂O; and

using the flow of respiratory gases to extract a pharmaceutical formulation from a receptacle and to place the pharmaceutical formulation within the flow of respiratory gases to form an aerosol.

2. A method as in claim 1 wherein the permitted flow of respiratory gases to the lungs is limited to a rate that is less than a certain rate.

3. A method as in claim 2 wherein the certain rate is about 15 L/min.

4. A method as in claim 2 wherein the certain rate is about 8 L/min.

5. A method as in claim 2 wherein the certain rate is sufficient to permit an inhaled volume that is in the range from about 125 mL to about 1.25 L.

6. A method as in claim 2 wherein the flow limiting step comprises providing feedback when an excessive flow rate is produced to permit a user to adjust their inhalation rate.

7. A method as in claim 2 wherein the flow limiting step comprises regulating the size of the airway leading to the lungs.

8. A method as in claim 7 further comprising regulating the size of the airway with a spring biased ball that is disposed within a tapered opening such that the ball is drawn into the opening as the flow rate increases.

9. A method as in claim 7 further comprising regulating the size of the airway to permit a flow rate greater than the certain rate after a period of time has elapsed.

10. A method as in claim 7 wherein the size of the airway is regulated by an elastomeric membrane having an opening, the size of the opening varying with the flow rate.

11. A method as in claim 10 wherein the elastomeric membrane is an elastomeric duckbill valve.

12. A method as in claim 2 further comprising providing another airway to permit a flow rate greater than the certain rate after a period of time has lapsed.

13. A method as in claim 2 wherein the permitted flow of respiratory gases to the lungs is limited to a rate that is less than the certain rate for a certain period of time.

14. A method as in claim 13 wherein the certain period of time is from about 0.5 seconds to about 5 seconds.

15. A method as in claim 1 wherein the valve comprises an occlusion member having an opening, and a pull through member that is pulled through the opening when the threshold actuating vacuum is produced.

16. A method as in claim 15 wherein the occlusion member comprises an elastomeric membrane, and wherein the pull through member comprises a ball.

17. A method as in claim 1 wherein the pharmaceutical formulation comprises a powdered medicament, and further comprising using the flow of respiratory gases to deagglomerate the extracted powder.

18. A method as in claim 1 wherein the receptacle comprises a receptacle body having a chamber which holds the pharmaceutical formulation, and further comprising placing the receptacle in a position in communication with the airway.

19. A method as in claim 1 wherein the threshold actuating vacuum is in a range from about 40 cm H₂O to about 60 cm H₂O.

20. A method as in claim 1 wherein the valve comprises a bistable member and wherein the bistable member moves from a first stable position to a second stable position when the threshold actuating vacuum is exceeded.

21. A method as in claim 1 wherein the pharmaceutical formulation is extracted downstream of the valve.

22. A method for administering a pharmaceutical formulation, the method comprising:

providing an inhalation device comprising a housing having a first opening to ambient air, a second opening to ambient air, a valve between said openings, and a mouthpiece at one of said openings;

preventing respiratory gases from flowing to the lungs when a user attempts to inhale through said mouthpiece;

permitting a first predetermined volume of respiratory gases to flow to the lungs, said first volume being sufficient to transport substantially all of a unit dose of a pharmaceutical formulation contained within the inhalation device out of the device and into the respiratory tract of a patient; and

permitting a second volume of respiratory gases to flow to the lungs.

23. A method as in claim 22 wherein the flow of respiratory gases is permitted by opening said valve when a threshold actuating vacuum by the attempted inhalation is exceeded.

24. A method as in claim 23 wherein said threshold actuating vacuum is from about 20 cm H₂O to about 60 cm H₂O.

25. A method as in claim 23 wherein said threshold actuating vacuum is greater than about 40 cm H₂O.

26. A method as in claim 22 wherein said first predetermined volume of respiratory gases is in the range from 125 mL to 1.25 L.

27. A method as in claim 22 further comprising regulating the flow of respiratory gases at a first flow rate until said first predetermined volume of respiratory gases flows through said device.

28. A method as in claim 27 wherein the first flow rate is less than 15 L/min.

29. A method as in claim 27 further comprising regulating the flow of said second volume of respiratory gases at a second flow rate.

30. A method as in claim 22 wherein the valve comprises a bistable member and wherein the bistable member moves from a first stable position to a second stable position when a threshold actuating vacuum is exceeded.

31. A method as in claim 22 wherein the pharmaceutical formulation is downstream of the valve.

32. An aerosolization device comprising:

a housing defining an airway;

a coupling mechanism adapted to couple a receptacle containing a pharmaceutical formulation to the airway; and

a valve to prevent respiratory gases from flowing through the airway until a threshold actuating vacuum is exceeded at which time the valve opens to permit respiratory gases to flow through the airway and to extract the pharmaceutical formulation from the receptacle to form an aerosol wherein the threshold actuating vacuum of the valve is in a range from about 20 cm H₂O to about 60 cm H₂O.

33. A device as in claim 32 further comprising a regulation system to regulate the flow of respiratory gases through the airway.

34. A device as in claim 33 wherein the regulation system is configured to limit the flow to a rate that is less than about 15 L/min.

35. A device as in claim 34 further comprising a flow integrator that is configured to open another airway in the housing after a certain period of time or a certain inhaled volume.

36. A device as in claim 34 wherein the regulation system limits the flow to a rate that is less than about 15 L/min for a certain period of time or for a certain inhaled volume.

37. A device as in claim 33 wherein the regulation system comprises a feedback mechanism to provide information related to the rate of flow of the respiratory gases.

38. A device as in claim 37 wherein the feedback mechanism comprises a whistle in communication with the airway.

39. A device as in claim 33 wherein the regulation system comprises a flow restrictor disposed in the airway, the flow restrictor defining an orifice sized to limit the flow of respiratory gases through the airway.

40. A device as in claim 39 wherein the flow restrictor comprises an elastomeric membrane to modulate the size of the airway.

41. A device as in claim 40 wherein the elastomeric membrane is an elastomeric duckbill valve that closes as the flow rate of the respiratory gases increases.

42. A device as in claim 39 wherein the flow restrictor comprises a spring biased ball that is drawn into a tapered opening as the flow rate of the respiratory gases increases.

43. A device as in claim 39 wherein the flow restrictor is adjustable to vary the rate of flow of respiratory gases through the airway.

44. A device as in claim 43 wherein the regulation system further comprises a control system to adjust the flow restrictor.

45. A device as in claim 44 wherein the control system is configured to limit the flow to a certain rate for a certain period of time or for a certain inhaled volume and then to adjust the flow restrictor to permit an increased flow of respiratory gases through the airway.

46. A device as in claim 32 wherein the valve comprises an occlusion member having an opening, and a pull through member that is pulled through the opening when the threshold actuating vacuum is produced.

47. A device as in claim 46 wherein the occlusion member comprises an elastomeric membrane, and wherein the pull though member comprises a ball.

48. A device as in claim 32 further comprising a deagglomeration mechanism disposed in the airway downstream of the receptacle to deagglomerate the extracted pharmaceutical formulation.

49. A device as in claim 32 wherein the valve is adapted to be disposed within the receptacle.

50. A device as in claim 32 wherein the device is adapted to removably receive the receptacle.

51. A device as in claim 32 wherein the threshold actuating vacuum is in a range from about 40 cm H₂O to about 60 cm H₂O.

52. A device as in claim 32 wherein the valve comprises a bistable member and wherein the bistable member moves from a first stable position to a second stable position when the threshold actuating vacuum is exceeded.

53. A device as in claim 32 wherein the valve is positioned so that the pharmaceutical formulation is extracted downstream of the valve.

54. A method for aerosolizing a pharmaceutical formulation, the method comprising:

placing a valve within an airway leading to the lungs to prevent respiratory gases from flowing to the lungs when a user attempts to inhale, and then abruptly permitting respiratory gases to flow to the lungs by opening the valve when a threshold actuating vacuum caused by the attempted inhalation is exceeded, wherein the threshold actuating vacuum is in a range from about 20 cm H₂O to about 60 cm H₂O; and

using the flow of respiratory gases to extract a pharmaceutical formulation from a receptacle and to place the pharmaceutical formulation within the flow of respiratory gases to form an aerosol.

wherein the receptacle comprises a penetrable portion above a chamber which holds the pharmaceutical formulation, and further comprising penetrating the penetrable portion to expose the pharmaceutical formulation.

55. An aerosolization device comprising:

a housing defining an airway;

a coupling mechanism adapted to couple a receptacle containing a pharmaceutical formulation to the airway; and

a valve to prevent respiratory gases from flowing through the airway until a threshold actuating vacuum is exceeded at which time the valve opens to permit respiratory gases to flow through the airway and to extract the pharmaceutical formulation from the receptacle to form an aerosol, wherein the threshold actuating vacuum of the valve is in a range from about 20 cm H₂O to about 60 cm H₂O,

wherein the device comprises a member adapted to penetrate a penetrable portion of the receptacle to expose the pharmaceutical formulation.