GB2310607A - Spacer device for inhalers - Google Patents

Abstract

The spacer, which is for attachment to the mouthpiece of a dry powder inhaler or pressurised MDI, has its own mouthpiece formation at the end remote from attachment and is associated with means for producing a pressure difference within the inhaler/spacer combination relative to ambient air pressure so as to generate a flow of air through the inhaler and achieve effective dose dispersion and delivery. Negative pressure may be generated inside the combination by expanding a transparent bellows which itself forms the spacer or the spacer volume may be changed by means of a piston/seal arrangement or deformable diaphragm. Alternatively, a vacuum chamber or store of pressurised gas may be used to produce the pressure difference.

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.

Spacers for use with such pressurised metered dose inhalers are well known. They usually serve one or two functions: So-called "small volume" spacers are used to reduce 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 5liy) 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.

In a first aspect, the invention is a spacer device adapted for attachment to the mouthpiece of a dry powder inhaler apparatus, said spacer device 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 spacer device is associated with means to produce a pressure difference within the inhaler apparatus/spacer device combination relative to ambient air pressure, 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.

Preferably, the mouthpiece formation on the spacer device is provided with a low resistance one-way valve allowing the patient to inhale from the spacer device but not to exhale into it. This prevents leakage of aerosol to atmosphere and possible hygroscopic agglomeration of aerosol particles.

Preferably, means are provided to control the release of the pressure difference created in the inhaler apparatus/spacer device combination. This may be done, for example, using a patient-operated valve system.

In one preferred embodiment, a negative pressure is generated inside the inhaler apparatus/spacer device combination. This may be produced by a separate chamber, or may be produced in some way by the spacer device itself. For example, the negative pressure may be generated by expanding a chamber such as a bellows, which might itself form the spacer device. The bellows is sealed at one end by the one-way valve in the new patient mouthpiece as already described, and at the other end by a second patientreleasable valve mechanism situated between the dry powder inhaler mouthpiece and the bellows volume.

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

As the patient inhales from the bellows volume, the dispersed medicament particles are inhaled. Large particles deposit within the bellows volume. The patient need not inhale at a fast flow rate, and will also be able to inhale over several breaths if desired. As a result, even children will be able to inhale from the spacer device an effective dose of dispersed particles.

During inhalation, either the bellows is arranged to relax to its contracted condition so that the pressure within the bellows remains at ambient, or air is allowed to flow in to the bellows. One route of entry for such air is through the inlet ports of the dry powder inhaler.

In an alternative version, the patient-releasable valve is closed after the dose is dispensed into the bellows volume and the bellows 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 spacer device to improve medicament dispersion.

If the bellows volume is constructed from essentially transparent material, the patient will be able to see the dispensed and dispersed volume of medicament prior to inhalation, thus reassuring the patient 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 spacer device, or by other mechanisms of changing the volume of the spacer device. 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.

In an alternative embodiment, a similar effect is created using a store of air or gas at a pressure greater than ambient. This has the advantage that a greater energy storage can be achieved in a smaller volume. In this embodiment, an outlet from a high pressure storage volume is connected to the air inlets of the dry powder inhaler. When the patient operates a release valve to release the high pressure volume, it expands through the dry powder inhaler producing a cloud of dispensed and dispersed medicament at the mouthpiece of the dry powder inhaler. This may be collected in a spacer device for inhalation by the patient. As described previously, such a spacer device will feature a patient mouthpiece and may include a one-way valve to allow only inspiration from the spacer device whilst preventing exhalation into it.

The spacer device is ideally manufactured in a transparent material to provide the patient visual feedback of dose dispensing.

For some dry powder inhalers, the airflow paths for dispensing the dose may be separate from additional inlet air ports provided to reduce the resistance to inhalation. In such devices, it may be desirable to allow for high pressure air to be applied to only some of these air inlets, with others being blocked or partially closed. Alternatively, different sources of pressurised air/gas could be applied to the other inlet ports.

A further advantage of this embodiment is that a pre-dried volume of air or gas can be used, thus avoiding any risk of moisture contamination to the metered dose of powder.

The high and low pressure options described above both represent storage of energy to create flow through the dry powder inhaler. It will be clear that there are many and various forms of storing energy to create such flow and those described are given by way of example only. Some alternative forms may be as energy stored in a spring used to move a piston, for example, or even energy stored as pressurised propellant. Clearly, electrical energy could also be used as an energy storage means.

In yet another variant, the two aforementioned techniques are combined to produce both a high and a low pressure. On actuation of the inhaler apparatus, air or gas is caused to circulate through the inlet ports of the dry powder inhaler and out of its mouthpiece. On exiting the mouthpiece, the volume containing dispensed and dispersed medicament is collected in the spacer device and then recirculated through the inlet ports and through the dry powder inhaler dispersion mechanism again. This is continued for as many cycles as desired, with the dispensed dose becoming ever more effectively dispersed. At this point, the patient simply inhales from the spacer device. As previously, fresh air/gas is then allowed to enter to restore the enclosed volume to ambient pressure.Optionally, circulation of the enclosed volume may be continued throughout the act of patient inhalation to maintain dispersion of the fine medicament particles.

This recirculation may be achieved using a small hand pump, such as a bellows or other shape deformable under hand pressure by the patient, and ap.propriate use of one-way valves. Alternatively, recirculation could be provided by a small fan and electric motor, offering the further advantage that turbulence close to the fan blades may assist medicament dispersion.

In an alternative embodiment, the medicament-containing cloud of air/gas is forcibly expelled from the spacer device in single or multiple puffs for the patient to inhale.

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 powered spacer device forms a part of the inhaler apparatus itself, i.e. any inhaler where a dose of medicament is dispensed prior to inhalation.

Claims (10)

1. A spacer device adapted for attachment to the mouthpiece of a dry powder inhaler apparatus, said spacer device 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 spacer device is associated with means to produce a pressure difference within the inhaler apparatus/spacer device combination relative to ambient air pressure, 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.

2. A spacer device as claimed in claim 1 wherein the mouthpiece formation on the spacer device is provided with a low resistance one-way valve allowing a patient to inhale from the spacer device but preventing exhalation into it.

3. A spacer device as claimed in claim 1 or claim 2 wherein means are provided to control the pressure difference created in the inhaler apparatus/spacer device combination.

4. A spacer device as claimed in claim 3 wherein the means to control the pressure difference is a patient-operated valve system.

5. A spacer device as claimed in any preceding claim wherein a negative pressure is generated inside the inhaler apparatus/spacer device combination by expanding a chamber, which itself forms the spacer device.

6. A spacer device as claimed in claim 5 wherein the chamber is a bellows sealable at one end by a one-way valve in the mouthpiece formation and sealable at the other end by a second patient-releasable valve mechanism situated between the inhaler mouthpiece and the bellows volume.

7. A spacer device as claimed in any one of claims 1 to 4 wherein the pressure difference is a combination of both high and low pressure and wherein, in response to actuation of the inhaler apparatus, air or gas is caused to circulate through the inlet ports of the inhaler and out of its mouthpiece to dispense a dose of medicament, said dose being collected in the spacer device and then recirculated through the inlet ports and through the inhaler dispersion mechanism again for as many cycles as desired to achieve effectivesdispersion of the dispensed dose of medicament.

8. A spacer device as claimed in claim 7 wherein circulation of the enclosed volume is continued throughout the act of patient inhalation to maintain dispersion of the medicament.

9. A spacer device as claimed in any preceding claim wherein the spacer device is constructed from transparent material.

10. A spacer device substantially as described herein.