WO2008027755A2

WO2008027755A2 - Use of electrostatics in an aerosol device

Info

Publication number: WO2008027755A2
Application number: PCT/US2007/076390
Authority: WO
Inventors: Avi Eliahu
Original assignee: Novo Nordisk A/S
Priority date: 2006-08-30
Filing date: 2007-08-21
Publication date: 2008-03-06
Also published as: WO2008027755A3

Abstract

A liquid-based aerosol dispensing system can comprise a nozzle membrane in a dielectric material through which liquid formulation is forced. The dielectric can be supported by a surface that has an opening in the nozzle region known as the nozzle slot. The nozzle slot serves as a conduit for the liquid formulation to enter the air channel. The liquid can exit the nozzles in the form of jets that pass through the nozzle slot into the air channel where they break up into aerosol particles. Liquid that does not form into jets remains on the surface of the nozzle membrane as ooze and does not aerosolize. First and second electrodes can be positioned on two sides of the nozzle slot. A voltage unit can provide a voltage difference between the first and second electrode. The electric field on the dielectric can be produced by the voltage unit and thus can increase the contact angle of ooze droplets and increase system efficiency.

Description

USE OF ELECTROSTATICS TO AFFECT CONTACT ANGLE IN AN AEROSOL DEVICE

Inventor: Avi Eliahu

CLAIM OF PRIORITY

[0001] This application claims priority from the following co-pending application, which is hereby incorporated in its entirety: U.S. Provisional Application No. 60/823,981 entitled: "USE OF ELECTROSTATICS TO AFFECT CONTACT ANGLE IN AN AEROSOL DEVICE", by Avi Eliahu, filed August 30, 2006, (Attorney Docket No. NOVO-01000US0).

BACKGROUND OF INVENTION

[0001] Embodiments of the present invention relate generally to portable aerosol devices, especially portable aerosol devices for the aerosolized delivery of drugs. [0002] Exemplary systems for the aerosolized delivery of drugs can force a liquid containing a drug through nozzles to create jets which break up into aerosol particles which are inhaled by a patient.

[0003] Efficient systemic delivery can involve delivering the aerosol deep into the lung so that the drug can efficiently reach the air/blood exchange membranes and migrate into the circulatory system. Targeting the lung requires careful control of the aerosol particle size in order to bypass the particle filtering and clearing functions of the bronchial airways.

[0004] It is typically desired to produce an aerosol which has relatively small consistent particle sizes with particles within a predetermined size range. In addition, it is desired to produce an aerosol such that measures of aerosol quality, such as particle size and dose emitted are not affected by ambient conditions such as temperature and/or relative humidity. SUMMARY OF INVENTION

[0005] One potential problem with aerosol devices that pass a liquid through nozzles to create an aerosol is that the earliest liquid through the nozzles can be under relatively low pressure such that jetting is not achieved and instead the liquid can come out as liquid ooze that remains on the nozzle surface. [0006] This ooze may never become aerosolized and can thus represent inefficiency in the system. The ooze can also create the requirement for a greater pressure in order for the liquid to penetrate the ooze, otherwise more ooze is created. This problem is exacerbated at low ambient temperatures where the formulation (and the ooze) has a lower viscosity and so an even greater pressure is required to penetrate it. The ooze remains in the device and thus can increase the recommended frequency of cleaning.

[0007] A reduction of the ooze can increase the system efficiency, reduce the required system pressure, reduce the dependency on ambient temperature, and reduce the recommended frequency of cleaning.

[0008] Embodiments of the present invention can create an electric field at the nozzle surface. This electric field can reduce the contact angle of ooze droplets at the nozzle and thus can eliminate or reduce the ooze problem.

BRIEF DESCRIPTION OF THE DRAWINGS [0009] Figure 1 illustrates an exemplary detail of an aerosol delivery unit.

[0010] Figure 2 illustrates an exemplary dosage form of one embodiment.

[0011] Figure 3 illustrates the exemplary aerosol delivery unit of figure 1 with a nozzle region of a dosage form positioned at a nozzle slot.

[0012] Figure 4 illustrates an aerosol delivery unit with an air column unit. [0013] Figures 5A and 5B illustrate the operation of an exemplary embodiment of the present invention.

DETAILED DESCRIPTION

[0014] An electric field applied to a dielectric material can change the contact angle of a liquid on the surface. This phenomenon has been known as EWOD (Electro-Wetting on Dielectric). Such an electric field can be used to increase the contact angle of the ooze on the nozzle surface and thus eliminate or reduce ooze from the system.

[0015] One embodiment of the present invention is a liquid-based aerosol dispensing system 100. The aerosol dispensing system 100 can have a nozzle slot 104 through which liquid jets that form the aerosol pass from the nozzles to the air channel before breaking up into aerosol particles.

[0016] The nozzle slot 104 can be any size or shape. The nozzle slot 104 can be formed in or connected to a wall 106 of an air channel (not shown). The wall 106 can be made of a non-conductive material, such as plastic.

[0017] The nozzle slot 104 can serve as a conduit for a liquid formulation to enter an air channel. The liquid can exit the nozzles in the form of jets that pass through the nozzle slot

104 into the air channel where they break up into aerosol particles. Liquid that does not form into jets remains on the surface of a nozzle membrane as ooze and does not aerosolize. [0018] First and second electrodes 108 and 1 10 can be positioned on opposite sides of the nozzle slot 104. The electrodes 108 and 110 can be made of a conductive material, such as a metal.

[0019] The liquid-based aerosol dispensing system 100 can be a portable unit powered by a battery 102. Different types of batteries can be used. The batteries can be standard sized cells, such as AA size batteries. The batteries can be disposable or rechargeable.

[0020] A voltage unit 112 can produce a voltage difference between the electrodes 108 and 110. The voltage unit 1 12 can convert a relatively low battery voltage difference into a more significant voltage difference using capacitors or other known techniques. This voltage difference can be used to generate an electric field that reduces the contact angle of the ooze on the surface. This can prevent ooze from spreading and thus reduce the amount of ooze through a nozzle that can be positioned at the nozzle slot, such as shown in figure 3 below.

[00211 In one embodiment, there is no conductive path between the first and second electrodes. In one embodiment, a dielectric layer can be used for the nozzle material. The dielectric layer can be any electrically insulative layer, such as Polyimide film like Kapton® available from DuPont. This can allow a static charge to build on the dielectric.

[0022] The voltage difference between the electrodes can be greater than five-hundred volts. In one example, the voltage difference can be a thousand volts or more.

[0023] A liquid formulation can be forced through a nozzle membrane in a dielectric material. The dielectric material can be supported by a clamp surface that has an opening in the nozzle region known as the nozzle slot

[0024] A dosage form 200 can be used. The dosage form 200 can be any type of container for the liquid to be aerosolized.

[0025] In the example of figure 2, the dosage form 200 includes a nozzle region 202 having a dielectric layer with nozzles through which the liquid passes under pressure to form liquid jets, which break up into aerosol particles. The nozzles can be sized to form relatively small aerosol particles. The nozzles in one embodiment are about one micron in diameter at the exit. One embodiment of a dosage form has a seven by sixty-four array of nozzles.

[0026] The dosage form 200 can include a blister 204 to store the liquid to be aerosolized. A peel channel 206 can be used to pass the liquid to the nozzle region 202 under pressure.

Mechanical pressure on the blister 204 can cause the liquid to be forced through the nozzle region 202. [0027] The aerosol generation device of the present invention can be loaded with a disposable dosage form of the type disclosed within U.S. Patents 5,497,763, 5,544,646, 5,660,166 and 5,718,222, all of which are incorporated herein by reference to disclose a aerosol generation device and a disposable container for containing a drug for aerosolized delivery. The dosage form can be part of a strip of dosage forms that can be automatically or manually advanced to replace a used dosage form in position at the nozzle slot. [0028] Figure 3 shows a nozzle region 202 of a dosage form 200 positioned between electrodes 108 and 110 at nozzle slot 104. [0029] Figure 4 shows a liquid based aerosol dispensing unit 400 with an air column unit 402. The aerosol can pass into the air column unit 402 through the nozzle slot 401. The aerosol can then be inhaled by a user through a mouth piece 404.,

[0030] Sensors 406 can be used to check the flow rate and/or other conditions in the air channel unit to time the disbursal of the aerosol into the air column unit. An electrically tripped plunger or other mechanism can push on the blister to produce the aerosol through the nozzle region.

[0031] Microprocessor 408 can be used to initiate the electric field at the nozzle slot before the aerosol is dispensed. The microprocessor 408 can also be part of a control circuit can be designed to monitor inhalation flow rate, total inhale volume, and other parameters, and commence generation of aerosol at a predefined optimal point during the inhalation. [0032] A heating element can be used to heat the liquid before the aersolization as well. A heating element of one embodiment is described in the U.S. Patent 6,845,216, hereby incorporated by reference. Heating the formulation does not eliminate the ooze but can reduce the ooze's viscosity such that it is more easily penetrable. The heating element adds to the energy burden of the device and may affect the usability of the device by increasing the time to dose and the frequency of battery charging or replacement.

[0033] Figure 5A and 5B show the operation of an exemplary embodiment. Dosage form 502 can positioned the nozzle slot 504. In example 5A, the ooze droplet 510 has a relatively small connect angle with the nozzle surface. Electrodes 506 and 508 shown in figure 5B can be used to provide an electric field to produce an ooze droplet 512 with a larger contact angle making it easier for the liquid to be aerosolized.

[0034] Increasing the contact angle can reduce ooze. The reduction of ooze can increase system efficiency, reduce the required system pressure, reduce the system dependence on ambient temperature, and reduce the need for cleaning. [0035] In one embodiment, the electric field can be applied to decrease the contact angle.

Decreasing the contact angle can also reduce system pressure and the dependence on ambient conditions by thinning out the ooze layer.

[0036) The use of the electric field can be a substitute for chemical processing of the nozzle region. Chemical processes performed on the surface of a top dielectric layer, such as plasma_treatments, have succeeded in increasing the contact, but these processes can be expensive and can complicate dosage form production. Additionally, the effect of plasma treatment can be neutralized by some sterilization processes.

[0037] The drug which is released to the patient may be in a variety of different compositions. For example, the drug may be an aqueous solution of drug, i.e., drug dissolved in water and formed into small particles to create an aerosol which is delivered to the patient.

Alternatively, liquid suspensions or dry powders may be used. Alternatively, the drug may be in a solution wherein a low-boiling point propellant is used as a solvent.

[0038] The amount of drug delivered to the patient can vary greatly depending on the particular drug being delivered. A wide range of drugs can be delivered. For example, drugs delivered could be drugs which have a systemic effect e.g., leuprolide, insulin and analogs thereof including monomelic insulin, or morphine; or a local effect in the lungs e.g., Activase, albuterol, or sodium cromoglycate.

[0039] The foregoing description of preferred embodiments of the present invention has been provided for the purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise forms disclosed. Many embodiments were chosen and described in order to best explain the principles of the invention and its practical application, thereby enabling others skilled in the art to understand the invention for various embodiments and with various modifications that are suited to the particular use contemplated. It is intended that the scope of the invention be defined by the claims and their equivalents.

Claims

What is claimed is: 1. A liquid-based aerosol dispensing system comprising: a nozzle slot though which liquid jets for an aerosol pass; a first electrode on a first side of the nozzle slot; a second electrode on a second side of the nozzle slot; and a voltage unit to provide a voltage difference between the first and second electrode.

2. The liquid-based aerosol dispensing system of claim 1, wherein the liquid jets for an aerosol pass through the nozzle slot into an air channel unit.

3. The liquid-based aerosol dispensing system of claims 1 , wherein the air channel unit has a mouthpiece.

4. The liquid-based aerosol dispensing system of claim 1, further comprising a dielectric material with nozzles through which liquid jets pass to the nozzle slot.

5. The liquid-based aerosol dispensing system of claim 4, wherein the dielectric material with nozzles is a part of a nozzle layer of a dosage form, the dosage form storing liquid that is aerosolized through the nozzle region.

6. The liquid-based aerosol dispensing system of claim 1, wherein the voltage unit is powered by a battery.

7. The liquid-based aerosol dispensing system of claim 1, wherein the voltage difference between the first and second electrodes during aerosolization is greater that 500 volts.

8. The liquid-based aerosol dispensing system of claim 1, wherein the liquid jets break up into an aerosol in an air channel unit.

9. The liquid-based aerosol dispensing system of claim 1, wherein the aerosol contains a pharmaceutically active compound.

10. A liquid-based aerosol dispensing system comprising: a nozzle slot though which liquid jets for an aerosol pass; a first electrode on a first side of the nozzle slot; a second electrode on a second side of the nozzle slot; and a voltage unit to provide a voltage difference between the first and second electrode, wherein a dosage form has a dielectric layer with nozzles to dispense the liquid jets that break up into aerosol, and wherein the dosage from is positioned to dispense the liquid jets through the nozzle slot.

1 1. The liquid-based aerosol dispensing system of claims 10, wherein the dosage form stores the liquid that is aerosolized.

12. The liquid-based aerosol dispensing system of claim 10, wherein the liquid jets for an aerosol pass through the nozzle slot into an air channel unit.

13. The liquid-based aerosol dispensing system of claims 10, wherein the air channel unit has a mouthpiece.

14. The liquid-based aerosol dispensing system of claim 10, wherein the voltage unit is powered by a battery.

15. The liquid-based aerosol dispensing system of claim 10, wherein the voltage difference between the first and second electrodes during aerosol izati on is greater that 500 volts.

16. The liquid-based aerosol dispensing system of claim 10, wherein the aerosol contains a pharmaceutically active component.

17. A method comprising: producing a electric field between electrodes at a nozzle slot; and pressurizing a pharmaceutically active compound through nozzles in a dielectric material in the presence of the electric field.

18. The method of claim 17, wherein the voltage difference between the electrodes is greater than 500 volts.

19. The method of claim 17, wherein the dielectric layer is part of a dosage form.

20. The method of claim 17, wherein the aerosol is inhaled by a patient.