Inhalation device

Abstract

The disclosure describes an inhaler having a dosing chamber in which medicament is aerosolized with a vibrator piezoelectric transducer. A spacer is provided between a face of the transducer and a wall of the dosing chamber.

Claims

1. An inhalation device comprising a dosing chamber configured for holding a dry powder pharmaceutical, and a vibrator for interaction with the dosing chamber to aerosolize the pharmaceutical, the inhalation device comprising: a spacer comprising an inner surface and an outer surface, the inner surface forms a through-hole in a center portion of the spacer, wherein the spacer is substantially circular in plan, the spacer is located around a perimeter of a face of the vibrator between the face of the vibrator and a bottom wall of the dosing chamber such that an air space is created by the through-hole in the center portion between the inner surface, the face of the vibrator and the bottom wall of the dosing chamber, wherein the spacer is a metal plate, and comprises a plurality of tabs that are coupled to a side of the vibrator, and wherein a stand-off sleeve is placed over the spacer and the vibrator to increase the air space and to stabilize the spacer.

2. The device of claim 1, wherein the vibrator comprises a piezo transducer assembly.

3. The device of claim 1, wherein the stand-off sleeve is formed of a biaxially-oriented polymer material.

4. The device of claim 1, wherein the spacer is segmented with one or more gaps.

5. A method for arranging a vibrator in a dry powder inhaler device, having a dosing chamber configured to hold the dry powder, said method comprising: positioning a spacer having an inner surface and an outer surface, the inner surface forms a through-hole in a center portion of the spacer, wherein the spacer is substantially circular in plan, around a perimeter of a face of the vibrator between the face of the vibrator and a bottom wall of the dosing chamber, wherein an air space is created by the through-hole in the center portion between the inner surface, the face of the vibrator and the bottom wall of the dosing chamber, wherein the spacer is a metal plate, and comprises a plurality of tabs that are coupled to a side of the vibrator, and wherein a stand-off sleeve is placed over the spacer and the vibrator to increase the air space and to stabilize the spacer.

6. The method of claim 5, wherein the vibrator comprises a piezo transducer.

7. The method of claim 5, wherein the stand-off sleeve is formed of a polymer material.

Description

(1) Further features and advantages of the present invention will be seen from the following detailed description, taken in conjunction with the accompanying drawings, wherein:

(2) FIG. 1 is a cross-sectional view of a piezoelectric actuator made in accordance with the present invention;

(3) FIG. 2 is a perspective view of a vibrator or transducer with a spacer element in accordance with the present invention;

(4) FIG. 3 is a perspective view showing details of a spacer element in accordance with the present invention; and

(5) FIG. 4 is a perspective view, partially in cross-section, showing a tension mechanism, transducer, a dose chamber, a spacer sleeve and a tension ring in accordance with the present invention.

(6) As used herein the term dosing chamber is intended to comprise a blister pack in which a pharmaceutical is held, for aerosolization and delivery to a patient as described, for example, in U.S. Pat. Nos. 5,694,920; 6,026,809; 6,142,146; 6,152,130; 7,334,577; 7,080,644; 7,810,495; 7,950,390; 8,322,338; 8,573,202; 7,318,434; 7,779,837; 8,474,452; 8,439,033 and U.S. Published Application 2011/0000481, the contents of which are incorporated herein by reference. The dosing chamber also may comprise a dosing chamber into which a controlled quantity of a pharmaceutical is introduced for aerosolization and delivery to a patient or a combined reservoir and dosing chamber configured to contain multiple doses of a pharmaceutical material as described, for example in PCT Application PCT/US2011/020252, the contents of which are incorporated herein by reference.

(7) As used herein, a pharmaceutical may comprise a dry powder pharmaceutical or a liquid pharmaceutical.

(8) The terms vibrator, transducer and piezo are all used interchangeably throughout this application.

(9) Referring to FIGS. 1-4 of the drawings, a vibrator or transducer assembly 10 in accordance with the present invention comprises a rigid cylindrical case 12 formed of, for example aluminum, that is closed at one end by a wall 13. A piezoelectric ceramic disc 14 is located within cylinder 12 on wall 13. A positive lead wire 16 is affixed to the inside surface of the piezoelectric disc 14 and a circuit board 15. Disc 14 is adhered to an interior surface of wall 13 using a silicone adhesive 18 to provide strain relief and an environmental seal. A negative lead line 20 is also attached to the circuit board 15, which in turn is encased or potted within a silicone adhesive 18.

(10) Although this configuration protects the piezo from external contamination, the bond between the ceramic piezo and the metal housing limits the amount of mechanical displacement that is possible. This places a restriction on the performance of the aerosol generator. It would be highly desirable to remove this restriction. The challenge is to provide more displacement to aerosolize the medication via synthetic jetting from a dosing chamber, without stressing the bond or the piezo, potentially damaging both. Thus, it is desirable to increase the resultant effect of the displacement of the piezo without compromising the overall robustness of the design.

(11) It was discovered that providing a small, essentially closed air space between a face of the vibrator or transducer and a wall of the dosing chamber 40, substantially increases performance. This was achieved by placing a small metal spacer 22 as shown in FIGS. 2-3, over the face of the vibrator or transducer assembly. The spacer creates an air gap between the transducer face and bottom membrane of the dosing chamber. It is believed that the interaction between the air gap and the film can cause the film to vibrate with a combination of modes. One mode resembles that of the transducer: a simple drum skin mode. Relative motion of the transducer and film in this mode compresses and expands the air, so that it acts like an axial spring. The other mode resembles a ripple; it has several wavelengths across the diameter of the film and can occur at a much larger amplitude than the drum skin mode. These ripples may be conducive to fluidizing the powder and increasing performance both in terms of how quickly jetting is established and the rate and extent of exiting the formulation from the dosing chamber.

(12) Referring in particular to FIG. 3, the spacer 22 comprises a generally flat disc having a plurality (preferably 3) of downwardly extending tabs 24 which are friction fitted over the wall 18 of the aluminum case 12. Tabs 24 also may be adhered to the case 12, e.g. using an adhesive or solder. Spacer 22 preferably is round, and has one or more gaps 30 in its circular path.

(13) Alternatively, as shown in FIG. 4 in order to further increase the air space and better stabilize the spacer 22, a tension and stand-off ring 26 may be fitted around the outer periphery of the aluminum case 12. Ring 26 preferably is formed of a resiliently deformable material, preferably a polymer material, more preferably a biaxially-oriented polyester material. In a preferred embodiment ring 26 is formed of a biaxially-oriented polyester film such as Melinex, which is available from Tekra, a division of EIS, Inc. of New Berlin, Wis. Ring 26 serves the multiple purposes of stabilizing and holding spacer 22 to the aluminum case 12, increasing the size of the air gap between the face of the vibrator or transducer and a wall of the dosing chamber, and sealing the vibrator or transducer to the wall of the dosing chamber.

(14) The drive circuit for driving the vibrator or transducer in accordance with the present invention may comprise a conventional transducer drive circuit. For example, the drive circuit that is used may comprise a drive circuit as described in our aforesaid U.S. patent application Ser. No. 12/392,686, the contents of which are incorporated herein by reference.

(15) For example, as described in our aforesaid U.S. patent application Ser. No. 12/392,686, the transducer receives power from power supply 10. Field effect transistors comprise an electronic switch that is opened and closed at the primary resonance frequency of the transducer. Alternatively, the drive circuit may be constructed with a single transistor. An inductor stores energy when the electronic switch is closed. When the electronic switch is open, all of the energy in the inductor is transferred to the transducer. A diode effectively disconnects the inductor from the transducer after the energy of the inductor has been transferred to the transducer, thereby insuring the maximum energy transfer during a cycle.

(16) Other waveforms may also be used. The primary requirement is that the drive waveform produces sufficient harmonic energy such that a secondary resonant frequency of the piezoelectric transducer is excited whereby a mechanical oscillation at the secondary resonance occurs. It also is possible to generate a waveform comprising two sinusoidal signals at two different frequencies corresponding to the primary and a secondary resonance frequency of the transducer. Any signal that has sufficient energy at both the primary and a secondary resonance frequency such that significant mechanical motion of the transducer face is created at both frequencies creates the motion of the piezoelectric transducer face that has the desired effect.

(17) In an embodiment of the present invention, the dry powder pharmaceutical may comprise an active pharmaceutical ingredient, optionally further comprising a carrier. The carrier may be lactose.

(18) In an embodiment, the active pharmaceutical ingredient may be an antiviral compound; a bronchodilator, optionally selected from a long acting muscarinic antagonist (LAMA) or a long-acting beta.sub.2-agonist (LABA); and/or a corticosteroid.

(19) Examples of appropriate antiviral compounds include MDT-637, ribavirin, palivizumab, RSV-IGIV, ALN-RSV01, BMS-433771, RFI-641, RSV604, BTA9881, TMC-353121, MBX-300, YM-53403, RV568, a RSV-F Particle Vaccine, and derivatives or pharmaceutically acceptable salts thereof.

(20) Examples of appropriate LAMAs include glycopyrronium, dexpirronium, tiotropium, oxybutynin, ipratropium, darifenacin, and derivatives or pharmaceutically acceptable salts thereof.

(21) Examples of appropriate LABAs include formoterol, salmeterol, indacaterol, olodaterol, bambuterol, and derivatives or pharmaceutically acceptable salts thereof.

(22) Examples of appropriate corticosteroids include budesonide, fluticasone, beclomethasone, flunisolide, triamcinolone, ciclesonide, loteprednol, fluorometholone, and derivatives or pharmaceutically acceptable salts thereof.

(23) In a further aspect, the invention comprises an inhaler of the first aspect for use in treating a respiratory disease.

(24) In an embodiment, the respiratory disease is selected from chronic obstructive pulmonary disease (COPD), asthma, acute bronchitis, acute respiratory distress syndrome (ARDS), emphysema, chronic bronchitis and respiratory syncytial virus.

(25) It should be emphasized that the above-described embodiments of the present device and process, particularly, and preferred embodiments, are merely possible examples of implementations and merely set forth for a clear understanding of the principles of the invention. Many different embodiments of the invention described herein may be designed and/or fabricated without departing from the spirit and scope of the invention. For example, by placing a stand-off sleeve over the end of the transducer assembly, the metal spacer on the face of the vibrator or transducer assembly may be eliminated. Alternatively, the spacer element may be an integral part of the transducer assembly. All these and other such modifications and variations are intended to be included herein within the scope of this disclosure and protected by the following claims. Therefore the scope of the invention is not intended to be limited except as indicated in the appended claims.