WO2000044425A1

WO2000044425A1 - Dispenser

Info

Publication number: WO2000044425A1
Application number: PCT/EP1999/009735
Authority: WO
Inventors: Stanley George Bonney
Original assignee: Glaxo Group Ltd
Current assignee: Glaxo Group Ltd
Priority date: 1999-01-30
Filing date: 1999-12-10
Publication date: 2000-08-03
Anticipated expiration: 2001-07-30
Also published as: AU3036700A; GB9901988D0

Abstract

There is provided a dispenser for dispensing medicament comprising a housing (101), locatable within said housing (101), a container (102) having an outlet member (103), wherein said container (102) is movable relative to the housing (101) to enable dispensing therefrom; and an actuation indicator (120) for detecting movement of the container (102) relative to the housing (101), wherein said actuation indicator (120) is on a carrier sleeve (110) which is mountable on the exterior of the housing (101) and separable therefrom, with the proviso that the actuation indicator (120) is not an inductive displacement transducer including one or more inductive elements, wherein said container (102) is comprised of, or has attached thereto a component comprised of, a material capable of disturbing the magnetic field creatable by the flow of electric current in said one or more inductive elements. There is also provided a system for training patients in the use of the dispenser.

Description

Dispenser

The present invention relates to an actuation recorder for recording the actuation profile of an inhalation device. In particular, the invention relates to an actuation recorder for use with a metered dose inhaler by means of which medicament contained in an aerosol container may be administered to a patient.

It is well known to treat patients with medicaments contained in an aerosol, for example, in bronchodilator therapy. It is also known to use for such therapy, medicaments which are contained in an aerosol and are administered to a patient by means of an inhalation device comprising a tubular housing or sleeve in which the aerosol container is located and an outlet tube leading out of the tubular housing. The aerosol containers used in such inhalation devices are designed to deliver a predetermined dose of medicament upon each actuation by means of an outlet valve member at one end which can be opened either by depressing the valve member while the container is held stationary or by depressing the container while the valve member is held stationary. In the use of such devices, the aerosol container is placed in the tubular housing with the outlet valve member of the container communicating via a support with the outlet tube, for example a nozzle or mouthpiece. When used for dispensing medicaments, for example in bronchodilation therapy, the housing is then held by the patient in a more or less upright condition and the mouthpiece or nozzle of the inhalation device is placed in the mouth or nose of the patient. The aerosol container is pressed towards the support to dispense a dose of medicament from the container which is then inhaled by the patient.

It may be understood that effective delivery of medicament to the patient using an inhalation device as described above is to an extent dependent on the patient's ability to co-ordinate the actuation of the device (e.g. firing of the aerosol) with the taking of a sufficiently strong inward breath. The required coordination can present difficulties to some patients, with the risk that these patients do not receive the appropriate dose of medicament. It is, thus, desirable to provide a means for the patient to monitor their correct usage of the inhalation device. Such means might be designed for everyday usage, or for use in a system for training patients in the correct usage of the inhalation device.

Various training systems have been described in the prior art. These typically involve the use of customised inhalers or apparatus incorporating or connected to various means for providing the patient with information about their correct (or incorrect) usage of the inhaler. Examples of such customised inhalers or apparatus include the inhaler described in W093/12823 which incorporates various sensors and microprocessors; the inhalation apparatus described at US- A-4,495,944 which includes various visual indicators to guide the patient; the biofeedback and training evaluation system described at US-A-4,984,158; and the apparatus and visual display method described at US-A-5, 333,106.

A disadvantage associated with' the use of such customised inhalers and apparatus is that the patient is trained with this customised equipment but then takes home and uses a standard inhalation device which is likely to have different shape, size, look and feel characteristics. In essence, therefore, the training system trains the patient to use the customised equipment rather than the inhalation device that will be taken home for everyday use.

The Applicants have now found that this disadvantage may be overcome by the use of a training device and system which is employed as an add-on to a standard inhalation device. The patient may thus be trained in the use of a device which is identical to (or indeed is) the device they take home with them after the training session for everyday use.

According to one aspect of the present invention there is provided a dispenser for dispensing medicament comprising a housing; locatable within said housing, a container having an outlet member, wherein said container is movable relative to the housing to enable dispensing therefrom; and an actuation indicator for detecting movement of the container relative to the housing, wherein said actuation indicator is on a carrier sleeve which is mountable on the exterior of the housing and separable therefrom; with the proviso that the actuation indicator is not an inductive displacement transducer including one or more inductive elements, wherein said container is comprised of, or has attached thereto a component comprised of, a material capable of disturbing the magnetic field creatable by the flow of electric current in said one or more inductive elements.

Suitably, the housing has a tubular portion, the container is movable within said tubular portion and said carrier sleeve is shaped for receipt by the tubular portion. Preferably, the carrier sleeve is snugly receivable by the tubular portion of the housing.

Suitably, both ends of the carrier sleeve are open. The first end opening enables mounting of the sleeve on the tubular portion. The second end opening enables the user to access the container for movement relative to the housing.

Suitably, one or more guide elements are provided to the tubular portion and/or the carrier sleeve to guide the receipt of the carrier sleeve by the tubular portion. The guide elements may for example, be mechanical guides such as tongue and groove arrangements. The guide elements may also for example, be visual guides such as colour coding arrangements.

Suitably, a first end of the tubular portion has a lip to prevent over-receipt of the carrier sleeve. Preferably, the lip and the leading end of the carrier sleeve are shaped to be engagable.

Suitably, the container is an aerosol container. Preferably, the dispenser as a whole is of the known metered dose inhaler type which delivers metered doses of medicament from a pressurised aerosol canister.

Suitably, the container is not in physical contact with, or mechanically coupled to, the actuation indicator. The movement of the container relative to the housing is thus, detected by a non-contact sensing technique.

In aspects of the present invention, the actuation indicator detects the movement of the container relative to the housing by means of a sensing technique selected from the group consisting of optical sensing, magnetic sensing or sensing using detection of capacitative effects. Optical sensing may be used to detect movement of the container relative to the housing by providing the container with a patterned outer surface, for example strips in a barcode type arrangement, and locating an optical sensor on the housing so that it points towards the patterned surface. Movement of the container relative to the housing alters the amount of the light source which reflects back into the optical sensor as the beam passes over the patterned surface. The strips may be arranged so that the direction of movement of the container can be detected.

Magnetic sensing may be used to detect the movement of the container relative to the housing by the use of a magnetic switch device. A reader is located on the sleeve and magnetic material positioned on the outer surface of the container. Movement of the can relative to the housing results in interruption of the magnetic signal of the magnetic material. Alternatively, a hall effect device can be used whereby a semiconductor measures the strength of the magnetic field of the magnetic material on the container.

Detection of capactitative effects may be used to detect movement of the container by adding a conductive sleeve to the housing. On actuation of the dispenser, movement of the container relative to the conductive sleeve results in a change in capacitance which can be measured.

Suitably, the housing is provided with an outlet, preferably in the form of a mouthpiece.

Suitably, the dispenser comprises a passage through which dispensed doses may pass from the container to said outlet.

Suitably, the container provides measured doses.

Suitably, the dispenser additionally comprises a tube connectable to a pressure transducer for measurement of pressure within the housing.

Suitably, the dispenser is actuable in response to the inward breath of a user. According to another aspect of the present invention there is provided a system for training users in the operation of a dispenser comprising a dispenser as described hereinabove in communication with a visual display unit capable of visually indicating actuation.

According to a further aspect of the present invention there is provided an actuation indicating device for use with a dispenser comprising a housing and a container which is movable relative to said housing, said actuation indicating device comprising a carrier sleeve which is mountable on the exterior of the housing of the dispenser and separable therefrom; and on said carrier sleeve, an actuation indicator for detecting movement of the container relative to the housing; with the proviso that the actuation indicator is not an inductive displacement transducer including one or more inductive elements, wherein said container is comprised of, or has attached thereto a component comprised of, a material capable of disturbing the magnetic field creatable by the flow of electric current in said one or more inductive elements.

Suitably, the actuation indicator detects the movement of the container relative to the housing by means of a sensing technique selected from the group consisting of optical sensing, magnetic sensing and sensing using detection of capacitative effects. Examples of the use of these sensing techniques are provided above.

Suitably, a tube connectable to a pressure transducer is provided to the carrier sleeve.

The actuation indicating device and dispenser is suppliable as a kit of parts.

The dispenser is used for dispensing medicament.

A dispenser according to the invention will now be described with reference to the accompanying drawings in which:

Fig. 1 is a sectional view of a known dispensing device; Fig. 2 is a side view of a kit of parts comprising a standard metered dose inhaler and an actuation indicating device in accord with the present invention;

Fig. 3 is a side view of the assembled kit of parts of Fig. 2.

Fig. 4 is a schematic representation of a- system in accord with the present invention;

Fig. 5 is a perspective view of a training system in accord with the present invention.

The standard metered dose inhaler shown in Fig 1 comprises a tubular housing 1 in which an aerosol container 2 can be located. The housing is open at one end (which will hereinafter be considered to be the top of the device for convenience of description) and is closed at the other. An outlet 3 leads laterally from the closed end of the housing 1. In the embodiment illustrated, the outlet 3 is in the form of a mouthpiece intended for insertion into the mouth of the patient but it may, if desired, be designed as a nozzle for insertion into the patient's nostril.

The aerosol container 2 has an outlet valve stem 4 at one end. This valve member can be depressed to release a measured dose from the aerosol container or, alternatively, the valve stem 4 can be fixed and the main body of the container can be moved relative to the valve member to release the dose.

As shown clearly in Fig 1 , the aerosol container 2 is located in the housing 1 so that one end protrudes from its open top. Spacer ribs (not shown) may be provided inside the housing to hold the external surface of the container 2 spaced from the internal surface of the housing 1. A support 5 is provided at the lower end of the housing 1 and has a passage 6 in which the valve stem 4 of the aerosol container 2 can be located and supported. A second passage 7 is provided in the support 5 and is directed towards the interior of the outlet 3.

Thus, when the parts are in the positions shown in Fig 1 , the protruding portion of the aerosol container 2 can be depressed to move the container relative to the valve stem 4 to open the valve and a dose of medicament contained in the aerosol will be discharged through the passage 7 and into the outlet 3 from which it can be inhaled by a patient. One dose will be released from the aerosol container each time it is fully depressed.

Fig. 2 shows a kit of parts comprising a standard metered dose dispenser (essentially identical to that shown in Fig. 1 ) and an actuation indicating device in accord with the present invention. The metered dose inhaler comprises a tubular housing 101 containing an aerosol container 102 and having an outlet 103 in the form of a mouthpiece. A lip 108 is provided to the exterior of the tubular housing 101 at the end of the tubular housing 101 which is closest to the outlet 103.

The actuation indicating device is seen to comprise a hollow tubular sleeve 110, which is sized and shaped to be Snugly receivable by the exterior of the tubular housing 101 of the dispenser. In the received position it may be seen that the leading end 112 of the sleeve 110 abuts the lip 108 on the exterior of the housing 101. In an improvement herein the leading end 112 of the sleeve 110 and the lip 108 are shaped for ease of engagement with each other.

The sleeve 110 is provided with an inductive element in the form of coil 120, which is tightly wrapped therearound. The inductive coil 120 is connectable as the inductive element in an electronic oscillator (not shown). The sleeve is also provided with a flexible tube 130, which is connectable to means for the measurement of pressure profile. The inductive coil 120 uses inductance to measure the position of the container relative to the housing. Since the inductive coil 120 measures the relative proximity of the container 102 to the housing 101 it may also be thought of as an inductive proximity detector. Fig. 3 shows the kit of parts of Fig. 2 in assembled form.

On actuation of the dispenser, the aerosol container 102 is moved relative to the housing 101 and hence relative to the inductive coil 120. This movement is detectable by the inductive coil 120 since it causes a change in the inductance of the coil such that the circuit oscillates at a different frequency. The actuation indicating devices of Fig 2 and Fig 3 are also provided with a first tube 130 positioned within the mouthpiece 103 wherein the first tube 130 is connectable to a first pressure transducer (not shown) for the measurement of pressure drop thereacross and hence, enabling measurement of airflow as the patient inhales. The first pressure transducer relies for measurement on the use of the housing 101 and aerosol container 102 as a resistance element and deriving the pressure across this resistance as the patient inhales.

A second tube may also be provided to the devices of Fig 2 and Fig 3 for the measurement by connection to a second pressure transducer (not shown) of the pressure profile on propelled release of medicament from the aerosol container 102. Subtracting therefrom the profile obtained from the first pressure transducer allows for the provision, of a flat baseline for the release profile even in the presence of a pressure fluctuations resulting from the patients inhalation through the mouthpiece 103. Alternatively, a differential pressure sensor could be used to subtract one pressure measurement from the other.

The inductive coil 120 and pressure transducers are each connectable to processing circuitry, which in turn is connectable to electronic computation or information storage means. A typical system is represented schematically in Fig 4.

The use of visual display means is of particular utility in the training of patients in the correct operation of the dispenser, since the actuation profile, inhalation profile and release profile may be visually represented. Fig. 5 shows a suitable training system in which the dispenser is connected to processing means 140. The processing means 140 are in turn connected to a visual display unit 150 having a display screen 160 on which are represented traces for the release 162, inhalation 164 and actuation 166 profiles.

The use of electronic computational and storage means is of particular utility in the comparison of pressure release profiles of different dispensers

Whilst the present invention has been described in detail in respect of a metered dose inhaler actuatable manually by the patient it will be appreciated that other actuation mechanisms can be substituted. In particular, the use of a breath operated inhaler in which the actuation is assisted, and is responsive to, preferably triggered by, the inward breath of the patient, is also envisaged.

The dispenser of the invention is suitable for dispensing medicament, particularly for the treatment of respiratory disorders. Appropriate medicaments may thus be selected from, for example, analgesics, e.g., codeine, dihydromorphine, ergotamine, fentanyl or morphine; anginal preparations, e.g., diltiazem; antiallergics, e.g., cromoglycate, ketotifen or nedocromil; antiinfectives e.g., cephalosporins, penicillins, streptomycin, sulphonamides, tetracyclines and pentamidine; antihistamines, e.g., methapyrilene; anti- inflammatories, e.g., beclomethasone dipropionate, fluticasone propionate, flunisolide, budesonide, rofleponide, mometasone furoate or triamcinolone acetonide; antitussives, e.g., noscapine; bronchodilators, e.g., ^' albuterol, salmeterol, ephedrine, adrenaline, fenoterol, formoterol, isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine, pirbuterol, reproterol, rimiterol, terbutaline, isoetharine, tulobuterol, or (-)-4-amino-3,5-dichloro-α-[[[6-[2-(2-pyridinyl)ethoxy] hexyl]methyl] benzenemethanol; diuretics, e.g., amiloride; anticholinergics, e.g., ipratropium, tiotropium, atropine or oxitropium; hormones, e.g., cortisone, hydrocortisone or prednisolone; xanthines, e.g., aminophylline, choline theophyllinate, lysine theophyllinate or theophylline; therapeutic proteins and peptides, e.g., insulin or glucagon. It will be clear to a person skilled in the art that, where appropriate, the medicaments may be used in the form of salts, (e.g., as alkali metal or amine salts or as acid addition salts) or as esters (e.g., lower alkyl esters) or as solvates (e.g., hydrates) to optimise the activity and/or stability of the medicament.

Preferred medicaments are selected from albuterol, salmeterol, fluticasone propionate and beclomethasone dipropionate and salts or solvates thereof, e.g., the sulphate of albuterol and the xinafoate of salmeterol.

Medicaments can also be delivered in combinations. Preferred formulations containing combinations of active ingredients contain salbutamol (e.g., as the free base or the sulphate salt) or salmeterol (e.g., as the xinafoate salt) in combination with an anti-inflammatory steroid such as a beclomethasone ester (e.g., the dipropionate) or a fluticasone ester (e.g., the propionate).

It will be understood that the present disclosure is for the purpose of illustration only and the invention extends to modifications, variations and improvements thereto.

The application of which this description and claims form part may be used as a basis for priority in respect of any subsequent application. The claims of such subsequent application may be directed to any feature or combination of features described therein. They may take the form of product, method or use claims and may include, by way of example and without limitation, one or more of the following claims:

Claims

CLAIMS:

1. A dispenser for dispensing medicament comprising

a housing;

locatable within said housing, a container having an outlet member, wherein said container is movable relative to the housing to enable dispensing therefrom; and

an actuation indicator for detecting movement of the container relative to the housing,

characterised in that said actuation indicator is on a carrier sleeve which is mountable on the exterior of the housing and separable therefrom

with the proviso that the actuation indicator is not an inductive displacement transducer including one or more inductive elements,

wherein said container is comprised of, or has attached thereto a component comprised of, a material capable of disturbing the magnetic field creatable by the flow of electric current in said one or more inductive elements.

2. A dispenser according to claim 1 , wherein the housing has a tubular portion, the container is movable within said tubular portion and said carrier sleeve is shaped for receipt by the tubular portion

3. A dispenser according to claim 2, wherein the carrier sleeve is snugly receivable by the tubular portion of the housing.

4. A dispenser according to either of claims 2 or 3, wherein one or more guide elements are provided to the tubular portion and/or the carrier sleeve to guide the receipt of the carrier sleeve by the tubular portion.

5. A dispenser according to any of claims 2 to 4, wherein a first end of the tubular portion has a lip to prevent over-receipt of the carrier sleeve. _{nΛ IΛ Λ Λ}-_ 00/44425

12

6. A dispenser according to claim 5, wherein said lip and the leading end of the carrier sleeve are shaped for relative engagement.

7. A dispenser according to any of claims 1 to 6, wherein the container is an aerosol container.

8. A dispenser according to any of claims 1 to 7, wherein said actuation indicator detects the movement of the container relative to the housing by means of a sensing technique selected from the group consisting of optical sensing, magnetic sensing and sensing using detection of capacitative effects.

9. A dispenser according to any of claims 1 to 8, wherein the housing is provided with an outlet, preferably in the form of a mouthpiece.

10. A dispenser according to claim 9, comprising a passage through which dispensed doses may pass from the container to said outlet.

11. A dispenser according to any of claims 1 to 10, wherein said container provides measured doses.

12. A dispenser according to any of claims 1 to 11, additionally comprising a tube connectable to a pressure transducer for measurement of pressure within the housing.

13. A dispenser according to any of claims 1 to 12, actuable in response to the inward breath of a user.

14. A system for training users in the operation of a dispenser comprising a dispenser according to any of claims 1 to 13 in communication with a visual display unit capable of visually indicating actuation of the dispenser.

15. An actuation indicating device for use with a dispenser comprising a housing and a container which is movable relative to said housing, said actuation indicating device comprising

RECTIFIED SHEET (RULE 91) ISA/EP a carrier sleeve which is mountable on the exterior of the housing of the dispenser and separable therefrom; and

on said carrier sleeve, an actuation indicator for detecting movement of the container relative to the housing;

16. An actuation indicating device according to claim 15, wherein said actuation indicator detects the movement of the container relative to the housing by means of a sensing technique selected from the group consisting of optical sensing, magnetic sensing or sensing using detection of capacitative effects.

17. An actuating indicating device according to either of claims 15 to 16, wherein a tube connectable to a pressure transducer is provided to the carrier sleeve.

18. Kit of parts comprising an actuating device according to any of claims 15 to 17 and a dispenser comprising a housing and a container which is movable relative to said housing.

19. Use of a dispenser according to any of claims 1 to 13 for dispensing medicament.