Devices and methods for nebulizing fluids for inhalation

• US 20030150446A1
• Filed: 01/07/2003
• Published: 08/14/2003
• Est. Priority Date: 01/07/2002
• Status: Active Grant

• Current Assignee: Novartis Pharma AG (Novartis Ag)
• Original Assignee: Aerogen, Inc. (Nektar Therapeutics)
• Inventors: Patel, Rajan, Klimowicz, Michael A.
• Granted Patent: US 7,360,536 B2
• Time in Patent Office: Days
• US Class Current: 128/200.14
• CPC Class Codes: A61M 11/005 using ultrasonics spraying or atomising liquids using ultrasonic vibrations in general B05B17/06
• CPC Class Codes: A61M 11/007 Syringe-type or piston-type sprayers or atomisers
• CPC Class Codes: A61M 15/0065 Inhalators with dosage or measuring devices A61M15/0028 takes precedence; dosage devices incorporated in aerosol cans B65D83/52
• CPC Class Codes: A61M 15/0066 with means for varying the dose size
• CPC Class Codes: A61M 15/0085 using ultrasonics spraying or atomising liquids using ultrasonic vibrations in general B05B17/06
• CPC Class Codes: A61M 2016/0021 with a proportional output signal, e.g. from a thermistor
• CPC Class Codes: A61M 2016/0024 with an on-off output signal, e.g. from a switch
• CPC Class Codes: A61M 2205/50 with microprocessors or computers
• CPC Class Codes: A61M 2205/583 by visual feedback
• CPC Class Codes: A61M 2205/584 having a color code
• CPC Class Codes: A61M 2205/8206 battery-operated
• CPC Class Codes: B05B 17/0646 Vibrating plates, i.e. plates being directly subjected to the vibrations, e.g. having a piezoelectric transducer attached thereto

Abstract

A nebulizer comprising an aerosol generator and a titration mechanism comprising a dosing mechanism, a screw assembly, a plunger and an actuator, wherein the dosing mechanism is rotatably mounted in the nebulizer and the plunger is mounted in the nebulizer to travel along a longitudinal axis substantially perpendicular to the plane of rotation of the dosing mechanism. The actuator is mounted to the nebulizer to travel in the direction of the longitudinal axis. The screw mechanism allows the rotation of the dosing mechanism to fix a variable distance of travel of the plunger based on the selected dose, without moving the plunger longitudinally. This allows the user to verify and if necessary correct the selected dose prior to any drug being released from the vial. Operation of the actuator causes longitudinal movement, through the screw mechanism, to the plunger. The actuator always moves a fixed distance along the longitudinal axis, while the plunger always moves a variable distance depending on rotation of the dosing mechanism to a selected dose.

Claims

1. A nebulizer comprising:

a medicine vial assembly containing a medicine fluid;

a reservoir assembly that engages the medicine vial assembly in fluid communication therewith;

an aerosol generator mounted in fluid communication with the reservoir assembly; and

a titration mechanism comprising;

a plunger situated to act upon the medicine vial assembly, a screw assembly mechanically engaged with the plunger, a titration control mechanism mechanically engaged with the screw assembly, and an actuator button situated to act upon the screw assembly to cause linear movement of the plunger;

wherein operation of the titration control mechanism selectively sets the linear distance the plunger will be caused to move when the actuator button is pressed, wherein movement of the plunger causes the plunger to act upon the vial assembly in such a manner so as to displace fluid from the vial assembly into the reservoir assembly, and wherein the fluid in the reservoir assembly can be ejected from the reservoir as a mist by operation of the aerosol generator.

2. The nebulizer of claim 1 wherein the medicine vial assembly further comprises a collar having a tab and the reservoir assembly comprises a detent that interlocks with the tab to hold together the vial assembly and the reservoir assembly.

3. The nebulizer of claim 2 wherein the tab interlocks with the detent to prevent uncoupling and holds the vial assembly and the reservoir assembly together.

4. The nebulizer of claim 1 wherein the medicine vial assembly further comprises a collar having a plurality of tabs and the reservoir assembly comprises a plurality of detents that interlock within the tabs to hold together the vial assembly and the reservoir assembly.

5. The nebulizer of claim 4 wherein the tabs interlock with the detents to hold the vial assembly and the reservoir assembly in mutual assembly with each other.

6. The nebulizer of claim 5 wherein the tabs interlock with the detents to prevent disassembly of the vial assembly and the reservoir assembly once they are assembled together.

7. The nebulizer of claim 1 wherein the reservoir assembly comprises a reservoir and a cannula in fluid communication with the reservoir and wherein the cannula engages in fluid communication with the medicine vial assembly.

8. The nebulizer of claim 7 wherein the reservoir assembly further comprises a channel connecting the cannula with the reservoir in fluid communication.

9. The nebulizer of claim 7 further comprising a valve that opens to permit fluid to move from the medicine vial into the reservoir and closes to prevent reverse flow of fluid from the reservoir to the medicine vial.

10. The nebulizer of claim 1 wherein the medicine vial assembly comprises a moveable portion that may be moved by advancement of the plunger.

11. The nebulizer of claim 2 wherein the medicine vial assembly comprises a vial containing medicine fluid, an opening of the vial and a movable stopper situated within the opening of the vial, wherein the plunger acts on the movable stopper when the actuator button is pressed thereby moving fluid out of the medicine vial.

12. The nebulizer of claim 10 wherein the reservoir assembly comprises a reservoir and a cannula in fluid communication with the reservoir and wherein the cannula is received within the medicine vial assembly.

13. The nebulizer of claim 12 wherein the cannula is received within the medicine vial and wherein movement of the plunger causes fluid to move from the medicine vial through the cannula into the reservoir.

14. The nebulizer of claim 1 wherein the reservoir assembly permanently engages the medicine vial assembly

15. A nebulizer comprising a container containing fluid, a reservoir in fluid communication with the container, an aerosol generator situated to eject fluid from the reservoir as an aerosol, a dose selection mechanism permitting a user to select an amount of fluid to be moved from the container into the reservoir, and an actuator moveably mounted on the nebulizer wherein operation of the actuator by a user causes the selected amount of fluid to be moved from the container into the reservoir.

16. The nebulizer of claim 15 further comprising a plunger moveably mounted in the nebulizer and wherein operation of the actuator moves the plunger to act upon the container and wherein the dose selection mechanism sets the distance of movement of the plunger.

17. The nebulizer of claim 15 further comprising a plunger moveably mounted in the nebulizer and wherein the distance of movement of the plunger is set by operation of the dose selection mechanism and the movement of the plunger is effected by operation of the actuator.

18. The nebulizer of claim 17 wherein the container comprises an opening and a moveable seal friction fit within the opening and wherein the plunger is positioned to act upon the moveable seal when the actuator is operated.

19. The nebulizer of claim 18 wherein the moveable seal is moved through the container by action of the plunger upon it.

20. The nebulizer of claim 19 wherein the container defines a longitudinal axis therein and the stopper is moved through the container in a direction parallel to the longitudinal axis.

22. The nebulizer of claim 15 wherein the dose selection mechanism comprises a knob that is rotatably mounted on the nebulizer, and the degree of rotation sets the distance of movement of the plunger and a visual indicator acted upon by rotation of the knob to provide a visual indication of the amount of fluid displaced by a selected distance of movement of the plunger.

23. The nebulizer of claim 22 wherein the visual indicator comprises a numerical display and numbers from 0 to a predetermined maximum and the numbers each correspond to the amount of fluid that will be displaced by a selected distance of movement of the plunger.

24. The nebulizer of claim 22 wherein the knob is rotatably mounted to rotate in a plane substantially perpendicular to the longitudinal axis of the container

25. The nebulizer of claim 22 wherein the knob is rotatably mounted to rotate circumferentially with respect to the longitudinal axis of the container.

26. The nebulizer of claim 20 further comprising a retainer that releasably captures the actuator when the actuator is fully moved a distance from an initial position to a predetermined actuation position.

27. The nebulizer of claim 26 further comprising a release mechanism operable to release the retainer to allow the actuator to return to an initial position from a predetermined actuation position.

28. The nebulizer of claim 27 further comprising a reset mechanism that resets the visual indicator from a selected fluid amount indication to a zero indication.

29. The nebulizer of claim 28 further wherein the release mechanism and the reset mechanism are linked together such that operation of the release mechanism causes operation of the reset mechanism to reset the visual indictor.

30. The nebulizer of claim 23 wherein the dose selection mechanism comprises an electronically operable numerical display and electronic circuitry responsive to rotation of the knob.

31. The nebulizer of claim 29 wherein the dose selection mechanism comprises an electronically operable numerical display and an electronic circuitry responsive to rotation of the knob such that rotation of the knob to select a particular distance of movement of the plunger causes the numerical display to display a value corresponding to the amount of fluid that will be displaced by a selected distance of movement of the plunger.

32. The nebulizer of claim 31 wherein the electronic circuitry is responsive to operation of the release mechanism such that operation of the release mechanism causes the numerical display to be reset to an initial numerical value.

21. The nebulizer of claim 21 wherein the actuator is moveably mounted to move in a direction substantially parallel to the longitudinal axis of the container.

33. A method of delivering a nebulized fluid for inhalation, comprising:

providing an aerosol generator;

providing a container containing a fluid to be nebulized;

providing a reservoir in fluid communication with the container and with the aerosol generator;

providing a moveable member positioned to act upon the container in a manner to displace fluid therefrom providing a screw assembly operable through a range of operating positions situated to act upon the moveable member to selectively limit the distance of movement of the moveable member;

selecting a distance of movement of the of the moveable member by operating the screw assembly to a selected operating position;

moving the moveable member through the selected distance of movement to displace fluid from the container into the reservoir; and

operating the aerosol generator to eject fluid from the reservoir as a nebulized fluid for inhalation.

34. The method of claim 33 wherein the container defines a longitudinal axis and the moveable member is moveable in a direction substantially parallel to the longitudinal axis.

35. The method of claim 34 further providing a visual indicator linked to the screw assembly such that operation of the screw assembly causes a visual indication corresponding to the distance of movement the moveable member can move for a selected position of operation of the screw assembly.

36. The method of claim 35 wherein the visual indicator is one of a liquid crystal display and a light emitting diode and the visual indicator is linked to the screw assembly by an electronic circuitry such that operation of the screw assembly causes the visual indicator to display one of a range of numerical values that corresponds to the distance of movement of the moveable member for a selected position of operation of the screw assembly.

37. The method of claim 35 wherein each of the numerical values corresponds to a precalculated fluid volume to be displaced from the container by movement of the moveable member a distance based on a selected position of operation of the screw assembly.

38. The method of claim 35 wherein the step of selecting a distance of movement of the of the moveable member by operating the screw assembly to a selected operating position is carried out by selecting a position of operation of the screw assembly based on a displayed numerical value.

39. The method of claim 33, further providing a selection knob linked to the screw assembly and a visual indicator linked to the selection knob such that operation of the selection knob causes operation of the screw assembly and operation of the visual indicator.

40. A nebulizer comprising:

a container containing fluid, a reservoir in fluid communication with the container, an aerosol generator situated to eject fluid from the reservoir as an aerosol, a dose selection mechanism permitting a user to select an amount of fluid to be moved from the container into the reservoir, and an actuator moveably mounted on the nebulizer wherein operation of the actuator by a user causes the selected amount of fluid to be moved from the container into the reservoir.

41. The nebulizer of claim 40 further comprising a plunger moveably mounted in the nebulizer and wherein the distance of movement of the plunger is set by operation of the dose selection mechanism and the movement of the plunger is effected by operation of the actuator.

42. The nebulizer of claim 40 wherein the container defines a longitudinal axis therein and the stopper is moved through the container in a direction parallel to the longitudinal axis.

43. The nebulizer of claim 40 wherein the actuator is moveably mounted to move in a direction substantially parallel to the longitudinal axis of the container.

44. The nebulizer of claim 40 wherein the dose selection mechanism comprises a knob that is rotatably mounted on the nebulizer, and the degree of rotation sets the distance of movement of the plunger and a visual indicator acted upon by rotation of the knob to provide a visual indication of the amount of fluid displaced by a selected distance of movement of the plunger.

45. The nebulizer of claim 40 wherein the visual indicator comprises a numerical display and numbers from 0 to a predetermined maximum and the numbers each correspond to the amount of fluid that will be displaced by a selected distance of movement of the plunger.

46. The nebulizer of claim 40 wherein the knob is rotatably mounted to rotate in a plane substantially perpendicular to the longitudinal axis of the container.

47. The nebulizer of claim 40 wherein the knob is rotatably mounted to rotate circumferentially with respect to the longitudinal axis of the container.

48. The nebulizer of claim 40 further comprising a retainer that releasably captures the actuator when the actuator is fully moved a distance from an initial position to a predetermined actuation position.

49. The nebulizer of claim 48 further comprising a release mechanism operable to release the retainer to allow the actuator to return to an initial position from a predetermined actuation position.

50. The nebulizer of claim 49 further comprising a reset mechanism that resets the visual indicator from a selected fluid amount indication to a zero indication.

51. The nebulizer of claim 50 further wherein the release mechanism and the reset mechanism are linked together such that operation of the release mechanism causes operation of the reset mechanism to reset the visual indictor.

52. A method of delivering a nebulized fluid for inhalation, comprising the steps of:

providing an aerosol generator, a container containing a fluid to be nebulized, a reservoir in fluid communication with the container and with the aerosol generator, a moveable member positioned to act upon the container in a manner to eject fluid therefrom, and a linkage mechanism coupled to the moveable member to selectively control the distance of movement of the moveable member,

selecting a distance of travel of the of the moveable member,

moving the moveable member to eject fluid from the container into the reservoir,

operating the aerosol generator to eject fluid from the reservoir as a nebulized fluid for inhalation.

53. A nebulizer comprising a titration mechanism, a dispensing mechanism aerosol generator;

the titration mechanism comprises;

a housing configured to receive a medicine vial defining a central axis therein,

a plunger movably mounted within the housing to travel to and fro substantially parallel to the central axis of a vial when such a vial is received within the housing,

an actuator button configured to move the plunger when said actuator button is pressed by a user;

a titration control mechanism operable to selectively control the distance of travel of the plunger when the actuator button is pressed, and

wherein the dispensing mechanism comprises;

a cannula, a reservoir comprising a lumen defined by a wall, and a delivery tube in fluid communication between the cannula and the reservoir lumen wherein the cannula is configured to engage in fluid communication with a medicine vial and wherein fluid can be moved from a medicine vial through the cannula and through the delivery tube to the reservoir; and

wherein the aerosol generator is mounted within the lumen wall of the reservoir such that when the aerosol generator is operated, fluid within the reservoir is moved from the reservoir and released therefrom as a mist.

54. The nebulizer of claim 53, wherein the titration control mechanism comprises a numerical indicator capable of providing a numerical value corresponding the distance of travel of the plunger that the titration control mechanism will provide for a selected numerical value provided by the numerical indicator.

55. The nebulizer of claim 54, wherein the numerical indicator is capable of providing a plurality of numerical values corresponding to discrete distances of travel of the plunger that the titration control mechanism will provide for a selected numerical value provided by the numerical indicator.

56. The nebulizer of claim 54, wherein the plurality of numerical values of the numerical indicator are indexed to discrete volumetric amounts corresponding to the volume of fluid displaced by a predetermined distance of travel of the plunger when a vial containing fluid is received within the titration control mechanism housing.

57. The nebulizer of claim 54, wherein the plurality of numerical values of the numerical indicator are indexed to discrete volumetric amounts corresponding to the volume of fluid displaced by a predetermined distance of travel of the plunger when a vial containing fluid is received within the titration control mechanism housing.

58. The nebulizer of claim 53 wherein the titration control mechanism further comprises a screw assembly that allows the plunger to travel a selected distance by a fixed distance of movement of the actuator button.

59. The nebulizer of claim 58, wherein the titration control mechanism comprises a numerical indicator capable of providing a numerical value corresponding the distance of travel of the plunger that the titration control mechanism will provide for a selected numerical value provided by the numerical indicator.

60. A nebulizer comprising:

a titration mechanism;

a vial assembly comprising a vial; and

an aerosol generator;

wherein the vial has a ratio of inside diameter to vial length of between about 1;

3.5 to about 1;

4.5.

61. The nebulizer of claim 60 wherein the ratio is about 1:

3.7 to about 1;

4.2.

62. The nebulizer of claim 60 wherein the ratio is about 1:

3.8 to about 1;

4.0.

63. The nebulizer of claim 60 wherein the ratio is about 1:

3.9.

64. A nebulizer comprising:

a titration mechanism;

a vial assembly comprising a vial; and

an aerosol generator;

wherein the vial has a ratio of inside diameter to vial length of between about 1;

3.0 and about 1;

3.8.

65. The nebulizer of claim 64 wherein the ratio is between about 1:

3.2 to about 1;

3.6.

66. The nebulizer of claim 64 wherein the ratio is between about 1:

3.3 to about 1;

3.5.

67. The nebulizer of claim 64 wherein the ratio is between about 1:

3.4 to about 1;

3.6.

68. The nebulizer of claim 64 wherein the diameter of the vial is about 12 mm and the effective length of the vial is about 38 mm.

69. The nebulizer of claim 64 wherein the diameter of the vial is about 12.0 mm and the effective length of the vial is about 37.7 mm.

70. A nebulizer comprising:

a titration mechanism;

a vial assembly;

and an aerosol generator, the aerosol generator comprising an aerosol element comprising palladium.

71. The nebulizer of claim 70, wherein the aerosol element comprises between about 50% and about 100% palladium.

72. The nebulizer of claim 70, wherein the aerosol element comprises palladium and nickel.

73. The nebulizer of claim 70, wherein the aerosol element consists essentially of palladium.

74. The nebulizer of claim 70, wherein the aerosol element consists of palladium.

75. A nebulizer comprising:

a titration mechanism;

a vial mechanism;

an aerosol generator; and

a switch responsive to inhalation by a user.

76. The nebulizer of claim 75 wherein the switch comprises a sensor to sense a pressure drop.

77. The nebulizer of claim 76, further comprising a mouthpiece and wherein the switch comprises a sensor to sense a pressure drop in the mouthpiece.

78. The nebulizer of claim 75, further comprising a controller, wherein the controller controls operation of the aerosol generator based on the switch responding to inhalation.

79. The nebulizer of claim 78, wherein the controller comprises a timing element.

80. The nebulizer of claim 79, wherein the controller is configured to operate the aerosol generator upon an inhalation and to cease operation of the aerosol generator after a predetermined time.

81. The nebulizer of claim 80, wherein the predetermined time is between about 3 seconds and about 5 seconds.

82. The nebulizer of claim 81, wherein the predetermined time is between about 3.5 seconds and about 4.5 seconds.

83. The nebulizer of claim 81, wherein the predetermined time is about 4 seconds.

84. A nebulizer comprising:

a titration mechanism;

a vial mechanism;

an aerosol generator for generating aerosol from a liquid; and

a switch responsive to the amount of liquid available to the aerosol generator.

85. The nebulizer of claim 84, wherein the aerosol generator comprises a comprises a vibratory aerosolization element and a vibratory element, and wherein the switch senses a change in amplitude of vibration based on a change in the amount of liquid in contact with the aerosolization element.

86. The nebulizer of claim 85, wherein the switch comprises a sensor configured to sense a change in amplitude of vibration of the aerosolization element.

87. The nebulizer of claim 86, further comprising a controller, the controller configured to control operation of the aerosolization element, and wherein the switch comprises the sensor and the control of the controller over the operation of the aerosolization element.

88. The nebulizer of claim 84, wherein the switch is configured to respond to depletion of liquid in contact with the aerosol generator.

89. The nebulizer of claim 88, wherein the switch causes the aerosol generator to cease operation at a predetermined level of liquid depletion.

90. The nebulizer of claim 89, further comprising a controller to control the operation of the aerosol in response to the switch.

91. The nebulizer of claim 84, wherein the switch is configured to respond to the addition of liquid in contact with the aerosol generator.

92. A nebulizer comprising:

a titration mechanism;

a vial mechanism;

an aerosol generator for generating aerosol from a liquid;

a

a first switch configured to respond to the presence of a predetermined minimum amount of liquid available to the aerosol generator; and

a second switch configured to respond to the absence of a predetermined minimum amount of liquid available to the aerosol generator.

93. The nebulizer of claim 92, wherein the aerosol generator comprises a vibratory aerosolization element and a vibratory element, and wherein the first switch and the second switch each comprise a sensor that senses a change in amplitude of vibration based on a change in the amount of liquid in contact with the aerosolization element.

94. The nebulizer of claim 93, wherein the first of the first switch is configured to detect a change in amplitude corresponding to the aerosolization element being first state with an absence of a predetermined amount of liquid in contact with it and the second state with a presence of a predetermined amount of liquid in contact with it, and the second switch is configured to detect a change in amplitude corresponding to the aerosolization element being first in a state with a presence of a predetermined amount of liquid in contact with it and a second state with an absence of a predetermined amount of liquid in contact with it.

95. A nebulizer comprising:

a titration mechanism;

a vial mechanism;

an aerosol generator; and

at least one light, the light providing information to a user on at least one of the operability of the nebulizer and the state of operation of the nebulizer.

96. A nebulizer comprising:

a titration mechanism;

a vial mechanism comprising a vial containing insulin; and

an aerosol generator.

97. The nebulizer of claim 96, wherein the aerosol generator further comprises a vibratory apertured aerosolization element and a vibratory element configured to vibrate the aerosolizatin element.

98. The nebulizer of claim 97, further comprising a reservoir, wherein the aerosolization element comprises a first face and a second face, and wherein the first face faces into the reservoir.

99. The nebulizer of claim 98, wherein the first face is concave.

100. The nebulizer of claim 99, wherein the second face is convex.

101. The nebulizer of claim 97, wherein the apertures are tapered to narrow from the first face toward the second face.

102. A nebulizer comprising:

a titration mechanism;

a vial mechanism;

an aerosol generator; and

a controller to control operation of the aerosol generator.

103. The nebulizer of claim 102, wherein the controller is configured to provide a fixed length of time for operation of the aerosol generator.

104. The nebulizer of claim 103, wherein the fixed time is between about 3 seconds and about 5 seconds.

105. The nebulizer of claim 104, wherein the fixed time is approximately 4 seconds.

106. A method of nebulizing a liquid, comprising:

providing a nebulizer comprising a titration mechanism, a vial mechanism and an aerosol generator;

instructing a user to inhale for B seconds; and

operating the aerosol generator to produce aerosol from the liquid for A seconds, wherein A and B represent real numbers.

107. The method of claim 106, wherein A is less than B.

108. The method of claim 107, wherein A=B−

N.

109. The method of claim 108, wherein N=1.

110. The method of claim 109, wherein B is approximately 5 seconds.

111. The method of claim 110, wherein the liquid is a drug for systemic administration.

112. The method of claim 111, wherein the liquid is insulin.

113. The method of claim 107, wherein the liquid is insulin.

114. The method of claim 108, wherein the liquid is insulin.

115. The method of claim 110, wherein the liquid is insulin.

116. A method of providing aerosolized insulin to a user, comprising:

providing a nebulizer comprising a titration mechanism, a vial mechanism, an aerosol generator, and a reservoir;

operating the titration mechanism to select a dose of insulin for inhalation;

actuating the titration mechanism to displace the selected dose of insulin from the vial mechanism and into the reservoir;

commencing inhalation through the nebulizer;

operating the aerosol generator;

ceasing operation of the aerosol generator while inhalation continues;

ceasing inhalation after cessation of operation of the aerosol generator.

117. A method of aerosolizing a liquid, comprising,

providing a nebulizer comprising an aerosol generator;

providing a titration mechanism in the nebulizer, the titration mechanism comprising a dosing mechanism, a screw mechanism, an actuator and a plunger, the plunger movable along a longitudinal axis within the nebulizer, the actuator movable a fixed distance X along the axis defined by the plunger and the dosing mechanism rotatable in a plane substantially perpendicular to the longitudinal axis;

providing a vial mechanism comprising a vial, the vial having a longitudinal axis and a movable seal movable along the longitudinal axis;

inserting the vial mechanism into the nebulizer such that the longitudinal axis of the vial is substantially parallel to the longitudinal axis of the plunger;

rotating the dosing mechanism to select a dose,

operating the screw mechanism, by rotating the dosing mechanism, to set a variable distance Y of travel of the plunger corresponding to a selected dose without imparting longitudinal travel of the plunger;

moving the actuator longitudinally the fixed distance X to move the plunger longitudinally the selected variable distance Y;

moving the movable stopper the variable distance Y by movement of the plunger the selected variable distance Y;

displacing a volume of liquid, corresponding to the selected dose, from the vial to contact the aerosol generator;

operating the aerosol generator to aerosolize the liquid.

118. The method of claim 117, wherein the aerosol generator comprises an aerosolization element having a first face, a second face and a plurality of apertures therethrough and wherein operating the aerosol generator comprises vibrating the aerosolization element.

119. The method of claim 117, further comprising inserting a reservoir into the nebulizer, and wherein the liquid is displaced from the vial into the reservoir.

120. The method of claim 117, wherein the nebulizer further comprises a reservoir, and wherein the liquid is displaced from the vial into the reservoir.

121. A nebulizer comprising:

a titration mechanism comprising a longitudinally moveable plunger, the movement thereof defining a longitudinal axis, a longitudinally moveable actuator to move the plunger, the movement of the actuator defining a longitudinal axis, and a screw mechanism to set the distance of travel of the plunger;

a rotatably mounted dosing mechanism, the rotation thereof defining an axis of rotation,

a vial mechanism comprising a vial defining a longitudinal access and a moveable seal moveable along the longitudinal access of the vial;

an aerosol generator; and

a controller to control operation of the aerosol generator,

wherein the longitudinal axis of the plunger and the longitudinal axis of the actuator are parallel, and wherein the dosing mechanism is rotatable in a plane substantially perpendicular to the longitudinal axes.

122. The nebulizer of claim 121, wherein the longitudinal axis of the plunger, the longitudinal axis of the actuator and the axis of rotation of the dosing mechanism are substantially coaxial.

123. The nebulizer of claim 122, wherein the axes are coaxial.

124. The nebulizer of claim 122 wherein the longitudinal axis of the vial is coaxial with the axis of rotation of the dosing mechanism.

125. A method of nebulizing a liquid comprising:

providing a titration mechanism comprising a longitudinally moveable plunger, the movement thereof defining a longitudinal axis, a longitudinally moveable actuator to move the plunger, the movement of the actuator defining a longitudinal axis, and a screw mechanism to set the distance of travel of the plunger;

providing a rotatably mounted dosing mechanism, the rotation thereof defining an axis of rotation,

providing a vial mechanism comprising a vial defining a longitudinal access and a moveable seal moveable along the longitudinal access of the vial;

providing an aerosol generator;

providing a controller to control operation of the aerosol generator,

placing the vial-mechanism within the nebulizer such that the longitudinal axis of the vial is substantially coaxial with the axis of rotation of the dosing mechanism;

rotating the dosing mechanism to select a dose;

moving the actuator to move the plunger such that fluid is dispensed from the vial;

operating the aerosol generator to nebulize the liquid.