WO2008029216A1

WO2008029216A1 - Apparatus and method for aerosol generation using piezo actuators which are controlled independently of each other

Info

Publication number: WO2008029216A1
Application number: PCT/IB2007/002400
Authority: WO
Inventors: Ola Nerbrink
Original assignee: Novo Nordisk A/S
Priority date: 2006-08-30
Filing date: 2007-08-21
Publication date: 2008-03-13

Abstract

A piezo driven aerosolization device is disclosed. Multiple piezo elements or actuators (30,31) are driven independently to drive a porous mesh (10). Liquid is applied to one side of the mesh and is aerosolized on the other. By controlling the phase shift between the piezo elements, backfire can be reduced. Aerosol generation can be optimized.

Description

APPARATUS AND METHOD FOR AEROSOL GENERATION USING PIEZO ACTUATORS WHICH ARE CONTROLLED INDEPENDENTLY OF EACH OTHER

This Application claims priority to U.S. Provisional Application Number 60/841,258, filed August 30, 2006, and European Patent Application No. EP 06122393.9 filed October 17, 2006. The contents of both applications are incorporated herein by reference in their entireties.

BACKGROUND OF THE INVENTION

The invention relates to a method and apparatus for generating aerosol. In one particular embodiment, a mesh is vibrated by actuating multiple piezo actuating elements. The invention is well-suited for aerosolizing drugs, hormones, and medications, such as insulin, for pulmonary delivery, but can be used in other areas and for other purposes.

Aerosols can be generated by mesh technology in a variety of ways. Piezo elements have long been used to vibrate a mesh having a certain pore size. The individual pores are often tapered and have a liquid applied on the wide side of the tapering. The aerosolization occurs from the small side of the tapered hole (See e.g., EP 0718046B1, which is hereby incorporated by reference). While these technologies do create aerosols, they often produce resonance frequencies and create backfire. Backfire occurs at the end of the aerosolization process when the liquid just fills the pores of the mesh and the wide side acts as the aerosol generating part. This has been described and used for the aerosolization of suspensions [see e.g. EP 0732 975 Bl] where the risk of clogging of the mesh is evident due to the size of the suspension particles compared to the small side of the mesh hole. In general, these systems employ a mesh having tapered pores, usually with the large portion of the taper on the bulk liquid side and a narrower taper on the aerosol exiting side.

These prior technologies often offer little ability to control the amplitude of the mesh movement and thus can result in poor control of aerosol generation.

SUMMARY OF THE INVENTION

According to one aspect of the present invention, a mesh with tapered holes is placed with a small bending between two piezo elements that can move longitudinally. The piezo elements are then made to vibrate simultaneously with the same frequency or with a phase shift between them. The tapered holes are preferably oriented with the large portion of the taper on the bulk fluid side and the small portion on the aerosol generating side.

The piezo elements can be made to vibrate longitudinally. This in turn will cause the flexible mesh to vibrate up and down. By controlling the vibration of the elements separately and/or independently, phase shift can be controlled. This in turn can allow for control of the amplitude of the mesh movement. By employing certain phase shifts, backfire can be reduced or eliminated.

For example, one membrane may be driven so that it pushes the membrane inward while the other actuator also pushes inward against the membrane. This will cause the membrane to move up. The actuators can then be activated to move outward thus pulling the membrane down. The "in" and "out" movement of each actuator can be controlled separately to opti- mize aerosol generation and can be varied depending upon numerous parameters, including how much liquid is left in the reservoir.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure Ia is a drawing depicting an embodiment of the present invention in an undriven state. Figure Ib depicts a mesh for use with an embodiment of the present invention. Figure Ic depicts the pores in the mesh of figure Ib.

Figure 2 shows an embodiment of the present invention where the piezo actuators are simultaneously moving inward to drive the mesh

Figure 3 shows wave forms where two piezo actuators are driven in phase. Figure 4 shows wave forms where two piezo actuators are driven out of phase.

DETAILED DESCRIPTION OF THE INVENTION

As is shown in Figure 1 a, a mesh 10 having pores (preferably tapered pores) is oriented between two piezo elements 30, 31. Liquid to be aerosolized is placed below the mesh 10, typically in a reservoir 15. The piezo elements or actuators 30 and 31 are connected to a controller 50. The controller 50 is preferably programmable and can control each element individually. The mesh 10 is preferably oriented in a slightly convex configuration as shown.

The controller 50 can be virtually any voltage wave form controller for example, a waveform generator capable of generating the correct driving waveform. This could be a standard function generator providing sine, triangle, sawtooth etc. waveshapes, but also a so called arbitrary waveform generator which can be programmed to generate any waveform conceivable. A linear amplifier, eg. Piezo Systems' Linear Amplifier model EPA- 104 (Piezo Systems, Inc, Cambridge MA, USA) may be used. This amplifier is designed to handle the high voltage levels and capacitive load of a piezo transducer.

In some embodiments the preferred frequency range for controlling each actuator is between 10khz and lOMhz (preferably 100khz to 1 Mhz).

As is shown in Figure Ib, the mesh 10 is preferably made from stainless steel, plastic materials or other inert metals such as palladium by electroforming or laser drilling etc. The pores 100 are typically tapered so that the entry point for the liquid is large. They may conically taper to a smaller exit diameter, as is shown in Figure Ic. Typical pore dimensions are 0.5 to 5 um preferably (0.5 to 50 um depending on application). The membrane may be square, rectangular, or even circular (for example as two half circle piezo elements bonded to a circular membrane). The membrane can also be made to be disposable and thus eliminate the need for regular cleaning. The membrane can also be made to be removed from the piezo elements without tools to allow a patient to affect changing of membranes. In some embodiments the membrane can be supplied as part of a drug reservoir and placed between the piezos by the user. In other embodiments, the reservoir and membrane may be supplied with the piezos.

As is shown in Figure 2, the piezo elements or piezo actuators 30 and 31 may be driven simultaneously to flex the membrane. The controller can be programmed to control each element individually. This can cause a phase shift and amplitude changes. In some embodiments, it is possible to monitor the amount of liquid remaining. As the volume of liquid decreases, it may be desirable to adjust the vibration of each element to optimize aerosol genera- tion and eliminate backfire. This can be done by having two independent wave form controllers acting on each of the piezo actuators bonded to the mesh. The wave form controller can be either 1 : phase shifted with respect to each other to counteract each other or 2: the amplitude could be adjusted independent of each other to impose counteracting movement on the mesh or 3: combinations of 1 and 2 above.

Figure 3 shows a wave form where the two piezo elements are driven at the same frequency. Figure 4 shows a waveform where the two piezo elements are driven and each is completely out of phase with the other. Of course, the piezo can be driven with various degrees of phase shift to optimize aerosol performance.

The present invention may be embodied in a hand-held portable inhalation device, such as an insulin inhaler. The device may be battery powered and may contain a dosing apparatus to deliver a precise dose to the reservoir 15 for aerosolization. Ln one embodiment, an insulin pen device such as a NovoPen III may be adapted to deliver the insulin or drug of interest to the reservoir. In other embodiments the mesh and reservoir may be part of a blister pack, such as those employed by the Aerx IDMS device as is described in US Patent Nos. 5394866, 5497764, and 5497763, which are hereby incorporated by reference.

Those skilled in the art will recognize various other aspects of this invention. The above disclosure is not intended to be limiting or to be a representation that any device or example discussed herein has actually be constructed. Those of skill in the art will appreciate that the above described invention can be embodied in many ways and the invention is not limited to one particular embodiment.

Claims

What is claimed is:

1. An apparatus for generating an inhalable aerosol comprising: a mesh containing pores and having an aerosol generating side, the mesh defining a general plane, a first piezo actuator associated with the mesh and that vibrates generally longitudinally relative to the general plane, a second piezo actuator associated with the mesh and that vibrates generally longitudinally relative to the general plane, and a controller connected to the first and second piezo actuators; wherein the mesh is located between the first and second piezo actuators and deflects convexly with respect to the aerosol generating side and wherein the controller is configured to independently control each actuator.

2. The apparatus of claim 1, wherein the controller is programmed to drive the first and second actuators in phase during initial aerosol generation for a first period of time, and wherein the program causes the controller to create a phase shift as aerosol generation progresses for a second period of time.

3. The apparatus of claim 2, wherein the program is configured to reduce backfire by independently adjusting the frequency of at least one of the first and second piezo actuators.

4. The apparatus of claim 1, 2, or 3, wherein the mesh has pore diameters in the range of 0.5 to 5 μm.

5. The apparatus of claim 1, 2, or 3, wherein the mesh is detachable relative to the actuators.

6. The apparatus of claim 5, wherein the mesh comprises a plastic material.

7. The apparatus of any of the previous claims, wherein the side of the mesh opposite the aerosol generating side is associated with a reservoir for a fluid.

8. The apparatus of claim 7, wherein the mesh defines a portion of the reservoir.

9. The apparatus of claim 8, wherein the mesh and the reservoir are provided as a unit, the reservoir being pre-filled with a drug formulation.

10. A method of controlling aerosol generation, the method comprising the steps of: a) placing a porous membrane between a first and a second piezo actuator, the membrane defining a general plane, and the piezo actuator being adapted to vibrate generally longitudinally relative to the general plane, b) placing a liquid on one side of the membrane, and c) controlling longitudinal vibration of the first actuator independently of longitudinal vibration of the second actuator in a manner that causes the membrane to flex and thereby generate an aerosol.

11. The method of claim 10, wherein the first and second actuators vibrate out of phase in a manner that minimizes backfire.

12. The method of claim 10, wherein the first and second actuators are vibrated in phase when there are large amounts of liquid to be aerosolized but vibrate out of phase as the liquid supply decreases.

13. A method of creating an aerosol comprising the steps of: a) independently driving a first piezo actuator that vibrates longitudinally corresponding to a general plane, b) independently driving a second piezo actuator that vibrates longitudinally in the general plane, c) independently adjusting the frequency of at least one of the first piezo actuator and the second piezo actuator such that when driven the first and second piezo actuators cause a mesh in a general plane located there between to vibrate, thereby creating an aerosol with reduced backfire.

14. The method of claim 13, wherein the first and second actuators are vibrated in phase for a first period of time and vibrate out of phase for a second period of time.

15. The apparatus of claim 7, wherein the mesh further comprises tapered pores with the large portion of the tapered pore is on the side associated with a reservoir of fluid.

16. The method of claim 10, wherein the side of the mesh opposite the aerosol generating side is associated with a reservoir for a fluid.

17. The method of claim 16, wherein the mesh defines a portion of the reservoir.

18. The method of claim 17, wherein the mesh and the reservoir are provided as a unit, the reservoir being pre-filled with a drug formulation.

19. The method of claim 13, wherein the side of the mesh opposite the aerosol generating side is associated with a reservoir for a fluid.

20. The method of claim 19, wherein the mesh defines a portion of the reservoir.

21. The method of claim 20, wherein the mesh and the reservoir are provided as a unit, the reservoir being pre-filled with a drug formulation.

22. An apparatus for generating an inhalable aerosol comprising: a mesh containing pores and having an aerosol generating side, the mesh defining a general plane, at least one first piezo actuator associated with the mesh and that vibrates generally longitudinally relative to the general plane, at least one second piezo actuator associated with the mesh and that vibrates generally longitudinally relative to the general plane, a controller connected to the at least one first and second piezo actuators programmed to drive the first and second actuators in phase during initial aerosol generation for a first period of time, and wherein the program causes the controller to create a phase shift as aerosol generation progresses for a second period of time; wherein the mesh is located between the at least one first and second piezo actuators and deflects convexly with respect to the aerosol generating side; and wherein the controller is configured to independently control each actuator such that during use the program is configured to reduce backfire by independently adjusting the frequency of at least one of the first and second piezo actuators.