WO1997031668A1

WO1997031668A1 - Power spacer

Info

Publication number: WO1997031668A1
Application number: PCT/GB1997/000562
Authority: WO
Inventors: Raymond John Bacon
Original assignee: Norton Healthcare Limited
Priority date: 1996-02-29
Filing date: 1997-02-28
Publication date: 1997-09-04
Also published as: GB2310607A; AU2223297A; GB9604294D0

Abstract

A vessel adapted for attachment to the mouthpiece of a dry powder inhaler is provided with its own mouthpiece formation at the end thereof remote from its point of attachment to the inlet in use. The vessel is associated with means to produce a negative pressure within the inhaler/vessel combination relative to ambient air pressure. The pressure difference serves to generate a flow of air through the inhaler at a flow rate sufficient to achieve effective dose dispersion and delivery of the dry powder medicament. Preferably, the mouthpiece formation on the vessel is provided with a low resistance one-way valve allowing a patient to inhale from the vessel but preventing exhalation into it. In a preferred variant, the negative pressure is generated inside the inhaler/vessel combination by expanding a chamber, such as a bellows, which may constitute a spacer. The bellows is preferably partly transparent.

Description

POWER SPACER

The present invention relates to medicament dispensing devices of the type used for dispensing discrete amounts of a medicament to be entrained in an air or gas stream. In particular the invention is concerned with devices of the dry powder metered dose inhaler type which are well known in the art of medicine for the treatment of respiratory complaints such as asthma.

The use of portable metered dose inhalers has become increasingly widespread in recent years owing to the fact that they enable the patient to administer an accurate dose of medicament when required. This is particularly useful for ambulant patients including those whose respiratory difficulties manifest themselves suddenly.

A standard pressurised metered dose inhaler consists of three main parts: a pressurised canister, an actuator body and a mouthpiece. The pressurised canister contains a mixture of active drug and propellant and is usually formed from a deep drawn aluminium cup portion having a lid portion crimped thereto which carries a metering valve assembly.

So-called "spacers" for use with such pressurised metered dose inhalers are well known. It is generally understood by persons skilled in the art that a spacer is a collection vessel, the purpose of which is the containment for a finite period of a drug or particle cloud dispensed from an inhaler apparatus. The drug or particle cloud may have associated excipient/diluent. One purpose of containment is to allow the characteristics of the cloud to alter prior to user inhalation so that the inspired dose is more effective. Another effect of containment is to capture the dispensed medicament in a fixed space from which it can be withdrawn by the user over a period of time. Without containment, the dispensed cloud is quickly dissipated by ambient air currents.

So-called "small volume" spacers are known to assist in the reduction of oropharyngeal deposition, particularly in cases where the medicament is a strong glucocorticosteroid formulation. The purpose of the spacer is to reduce local side effects in the mouth {eg oral Candida, etc). This is achieved by reducing the proportion of large particulate matter entering the mouth. Unless they are trapped before inspiration, large particles (typically having a mean diameter greater than about 5μm) are likely to be deposited in the oropharyngeal region rather than in the bronchial tubes. Large volume spacers serve a similar function but, in addition, reduce the need for accurate coordination between inhalation and actuation of the inhaler.

Inhalers are also known for the administration of a metered dose of medicament in dry powder form. A dry powder inhaler also consists of three main parts: a powder storage zone, a surrounding body and a mouthpiece. Most dry powder inhalers are regarded as breath actuated because dose administration occurs as a result of inhalation by the user. However, this does not address the problem of reducing the number of large particles that may be deposited in the oropharyngeal region. Placement of a small volume spacer, optionally fitted with one or more impaction surfaces, on the front end of a dry powder inhaler has been described in International Patent Application No. WO 93/18811 . However, it is thought that this may affect the inhalation characteristics of the device. Furthermore, the characteristics of the dispersion systems used in many dry powder inhalers may mean that a simple small volume spacer attached to the inhaler does not reduce the amount of large particulate matter adequately. As far as the Applicant is aware, the combination of a dry powder inhaler with a small volume spacer is not common practice at the date of the present invention.

A further problem with dry powder inhalers is that, in order to achieve effective powder dispersion, the patient has to inhale at a reasonable flow rate against a significant restriction. Sufficient energy must be expended to cause breakup of the powder into fine particles. In other words, the patient must be able to exert a certain amount of power by inhalation in order for the dry powder inhaler to function effectively. If the patient is unable to inhale at a fast enough rate through the device, the usual result is either incomplete dose dispensing and/or ineffective dose dispersion into the range of fine particle sizes considered necessary for effective therapy. For this reason, all current proprietary dry powder inhalers are regarded as unsuitable for children under about five years of age. Many young children are unable to generate the minimum flow rate through the device for achievement of an effective dose dispersion and delivery.

In addition, in severe episodes of some respiratory complaints, a patient may be unable to inhale effectively against a substantial resistance or to inhale a substantial volume in a single inspiratory manoeuvre.

A further problem with some dry powder inhalers is that the patient is unable to see, hear, taste or feel the dose being delivered. This can lead to patient anxiety about whether or not a dose has been delivered and, according to some literature, may lead to patients taking extra doses in an attempt to gain some reassurance that they have taken their medication.

It is an object of the present invention to provide a system for dry powder inhalers that will reduce oropharyngeal deposition. It is a further object of the invention to render such devices more easily useable by patient groups who otherwise may have difficulty using such devices in an optimal fashion. These groups include children, and patients undergoing severe attacks or episodes of diseases such as asthma. It is yet another object of this invention to provide visual feedback to the patient that a dose of medicament has been dispensed and is available for inhalation. It is a still further object of the present invention to provide means to improve the dispersion of a metered dose of medicament into so-called respirable particles, thereby enabling an effective therapeutic dose to be achieved with a smaller actual dispensed dose of medicament.

The invention is a vessel adapted for attachment to the mouthpiece of a dry powder inhaler apparatus, said vessel having its own mouthpiece formation at the end thereof remote from its point of attachment to a dry powder inhaler apparatus in use; characterised in that said vessel includes means operable to generate a negative pressure relative to ambient air pressure within the inhaler apparatus/vessel combination, said pressure difference serving to generate a flow of air through the inhaler apparatus at a flow rate sufficient to achieve effective dose dispersion and delivery into the vessel. In one preferred embodiment, the negative pressure may be generated by expanding a chamber, such as a bellows. The vessel may be a spacer device, or it may be in a collapsed form which is capable of expansion into a spacer device. The expansible chamber or bellows may itself be constituted by the spacer device.

Preferably, means are provided to control the release of the pressure difference created in the inhaler apparatus/vessel device combination. This may be done, for example, using a user-operated valve system. Typically, the user will be the patient requiring the medicament, but some patients, such as the seriously infirm and very young children, may be assisted by another person in the use of their inhalation apparatus. The term "user" is therefore adopted throughout the present specification wherever such a possibility exists.

The mouthpiece formation on the vessel may be provided with a low resistance one-way valve allowing the patient to inhale from the vessel but not to exhale into it. This prevents leakage of aerosol to atmosphere and possibly hygroscopic agglomeration of aerosol particles. The other end may be sealed by a second user-releasable valve mechanism situated between the dry powder inhaler mouthpiece and the vessel interior.

In operation, the vessel is attached to the dry powder inhaler mouthpiece and expanded with both valves closed. This creates an enclosed volume at negative pressure relative to ambient. Once extended, the user-releasable valve mechanism is opened at the dry powder inhaler mouthpiece by the user. This causes a flow of air through the dry powder inhaler similar to the flow created by patient inspiration. The dose is dispensed and distributed as a cloud of dispersed particles into the enclosed volume of the vessel. The patient is then able to inhale easily from the vessel mouthpiece as the air pressure in the vessel becomes equilibrated with the outside air.

As the patient inhales from the vessel, the dispersed medicament particles are inhaled. Large particles deposit within the vessel. The patient need not inhale at a fast flow rate, and is also able to inhale over several breaths if desired. As a result, even children are able to inhale from the vessel an effective dose of dispersed particles. During inhalation, either the vessel is arranged to relax to a contracted condition so that the pressure within the vessel remains at ambient, or air is allowed to flow into the vessel interior. One route of entry for such air is through the inlet ports of the dry powder inhaler. In an alternative version, the user-releasable valve is closed after the dose is dispensed into the vessel and the vessel is then arranged to be compressed to cause the dispersed dose to be emitted gently from the patient mouthpiece, either as one or several puffs. This might be useful for administering aerosols to intubated patients. There may be a further dispersion nozzle at the patient mouthpiece of the vessel to improve medicament dispersion.

If the vessel is at least partially constructed from essentially transparent material, the user will be able to see the dispensed and dispersed volume of medicament prior to inhalation, thus reassuring the user that a dose has been dispensed and is available for inhalation.

It will be apparent to persons skilled in the art that a similar effect can be achieved by a variety of mechanisms, such as an additional vacuum chamber attached to the vessel, or by other mechanisms of changing the volume of the vessel. This could be achieved, for example, using a piston and a sliding seal or rolling seal, or by utilising another deformable shape or volume, such as a diaphragm.

It will also be clear that such a device could be an add-on device or could be an integral part of a dry powder inhaler or even a pressurised metered dose inhaler. Although the invention has been described above with particular reference to its applicability to dry powder inhalers, it may be equally applicable to other forms of inhaler in which a dose of medicament is metered, or provided in a single metered dose format. The concept of the power spacer is intended to include both add-on devices, whether generic or specific to a particular inhaler, and integral devices, where the power spacer device forms a part of the inhaler apparatus itself, i.e. any inhaler where a dose of medicament is dispersed prior to inhalation.

Claims

1. A vessel adapted for attachment to the mouthpiece of a dry powder inhaler apparatus, said vessel having its own mouthpiece formation at the end thereof remote from its point of attachment to a dry powder inhaler apparatus in use; characterised in that said vessel includes means operable to generate a negative pressure relative to ambient air pressure within the inhaler apparatus/vessel combination, said pressure difference serving to generate a flow of air through the inhaler apparatus at a flow rate sufficient to achieve effective dose dispersion and delivery into the vessel.

2. A vessel as claimed in claim 1 wherein the means for generating negative pressure inside the inhaler apparatus/vessel combination is an expansible chamber.

3. A vessel as claimed in claim 1 or claim 2 wherein the vessel is a spacer device.

4. A vessel as claimed in claim 3 wherein the spacer device itself constitutes the expansible chamber.

5. A vessel as claimed in claim 2 or claim 4 wherein the means to generate a negative pressure relative to ambient air pressure is biasing means operable between an actuating condition and a relaxed condition, said relaxed condition of the biasing means corresponding to an expanded condition of said chamber.

6. A vessel as claimed in claim 5 wherein said biasing means is a spring having stored energy in said actuating condition, said stored energy being releasabie by a user.

7. A vessel as claimed in claim 2 and any one of claims 4 to 6 wherein the expansible chamber comprises a bellows.

8. A vessel as claimed in any preceding claim wherein means are provided to control the pressure difference created in the inhaler apparatus/vessel combination.

9. A vessel as claimed in claim 8 wherein the means to control the pressure difference is a user-operated valve system.

10. A vessel as claimed in any preceding claim wherein the mouthpiece formation on the vessel is provided with a low resistance one-way valve allowing a user to inhale from the vessel but preventing exhalation into it.

11. A vessel as claimed in claim 2 and any one of claims 4 to 10 wherein the expansible chamber is sealable at one end by a one-way valve in the mouthpiece formation and sealable at the other end by a second user-releasable valve mechanism situated between the inhaler mouthpiece and the chamber volume.

12. A vessel as claimed in any preceding claim wherein at least a portion of the vessel is constructed from transparent material.