WO2002089882A1

WO2002089882A1 - Gauge

Info

Publication number: WO2002089882A1
Application number: PCT/GB2002/002067
Authority: WO
Inventors: Philip Braithwaite
Original assignee: Ml Laboratories Plc
Priority date: 2001-05-10
Filing date: 2002-05-10
Publication date: 2002-11-14
Also published as: GB0111337D0

Abstract

There is described a medicament delivery device which comprises a medicament reservoir, a metering member and a delivery channel characterised in that the metering member is adapted to deliver a preselected dosage of medicament from a range of dosages and the delivery device is provided with an indicator means for gauging the capacity of the medicament reservoir. There is also described an inhaler comprising such a delivery device and a method of treatment related thereto.

Description

Gauge

This invention relates to a novel form of delivery device, a novel method of delivery and a novel method of treatment related thereto.

There is an increased interest in the delivery of powders e.g. powdered medicaments. Such medicaments may be administered orally due to their enteral activity or may be administered orally into the lung, e.g. by inhalation. Increasingly, with certain medicaments, for example, steroids, there may be a desire to administer a relatively high dose on initiation of the therapy but titration downwards to a lower dose following initial control of symptoms. Similarly, if the symptoms recur, there may be a desire to titrate the dose up again.

One example of such desired control is in the delivery of medicaments, e.g. a steroid, in the treatment or alleviation of respiratory disorders, such as asthma.

hi a powder delivery device, for example, a dry powder inhaler (DPI) it is necessary to accurately and reliably deliver a measured amount of powder, e.g. powdered medipament.

Dry powder inhalers are known, such as CLICKHALER, produced by h novata Biomed in the UK. Such a device is described in European Patent No 0 539 469.

One disadvantage with inhalers generally is that they are not suited to administering a variable dosage of medicament. For example, a medical practitioner may wish to vary the dosage of medicament depending upon the severity of, e.g. an asthma attack or due to other extraneous circumstances.

Furthermore, in known inhalers which may be capable of varying the dose of the medicament, the patient may find it difficult to gauge when the inhaler is empty or nearly empty or track how many doses have been taken. We have now found a novel mechanism which is adapted to better monitor the capacity of a reservoir. Indeed the novel mechanism offers the advantage that, inter alia, a patient can ensure that a reservoir is empty and therefore need not unnecessarily discard the delivery device, e.g. an inhaler. Although inhalers, e.g. dry powder inhalers are referred to hereinafter, it should be understood by the skilled man that the present is applicable to any powder delivery device.

Thus according to the invention we provide a medicament delivery device which comprises a medicament reservoir, a metering member and a delivery channel characterised in that the metering member is adapted to deliver a preselected dosage of medicament from a range of dosages and the delivery device is provided with an indicator means for gauging the capacity of the medicament reservoir.

The indicator means is adapted to be moved firom a first position each time that the metering member dispenses a dosage of medicament to a second position and wherein means is provided to indicate the dosage removed and/or the remaining capacity of the reservoir. Thus, the metering member may move from a metering or measuring position to a dispensing position and, in doing so, moves the indicator means from a first position to a second position.

In a preferred embodiment the metering member is provided with engaging means which is adapted to engage either directly or indirectly with the indicator. The size, e.g. the capacity, of the engaging can very depending on the capacity of the metering member. Thus, the size of the metering member engaging means will engage with indicator engaging means and will move the indicator to a greater or lesser degree, ^• depending upon, inter alia, the size of the metering member.

In an especially preferred embodiment the engaging means may comprise a toothed member. Thus, the indicator engaging means may comprise a toothed wheel e.g. a cog. I such a case the metering member means may comprise one or more teeth adapted to engage the cog. Preferably, the number of teeth provided to the metering member may vary depending upon the capacity of the metering member. Thus, there may be a relationship between the capacity and the number of teeth. For example, such a metering member may be provided with 1 tooth for every 10 μg of capacity or 1 tooth for every 100 μg of medicament powder formulation. Thus, for example a metering member may comprise four measuring cups of 10 μg, 20 μg, 30 μg and 40 μg capacity or 100 μg, 200 μg, 300 μg and 400 μg capacity and, respectively 1, 2, 3 and 4 teeth associated with each measuring cup. It should be understood that the dosages referred to herein are intended to be illustrative only and should not be considered limiting. By way of example only, a dispensing member may be provided with a plurality of different sized metering members, e.g. which have a capacity of 10 μg, 20 μg, 30 μg and 40 μg of medicament. In such a case the dispensing member and/or the metering member may be provided with 1 tooth, 2 teeth, 3 teeth and 4 teeth respectively. In an especially preferred embodiment the dispensing member and/or metering member will be provided with a tooth or a plurality of teeth adjacent the metering member, e.g. a metering cup, and substantially no teeth are provided in between the metering member or cup region. Thus, the region between the metering members may be substantially smooth. In this preferred embodiment of the invention, the metering member will engage with the indicator, e.g. the cog, when moving to a dispensing position. Once the powder has been dispensed, the metering member will disengage from the indicator and return, e.g. rotate in the opposite direction, to a metering position. Thus, for example, the metering member may comprise biasing, e.g. a helical spring, to enable the return to occur.

The delivery device of the invention may comprise any conventionally known medicament device. However, the mechanism of the present invention is especially suited for use as an inhaler, including, for example, a DPI, an insufflator and a nebuliser.

By the term inhaler used herein, it is intended to mean any of the aforementioned devices, hi a preferred embodiment, the inhaler of the invention may comprise a DPI. Furthermore, although oral administration is referred to, it would be well understood by the skilled man that the delivery device may be suitable for use in relation to other routes of administration, e.g. nasal administration.

Thus according to the invention we provide a delivery device as hereinbefore described characterised in that the device is an inhaler.

The medicament reservoir may be a bulk reservoir, in which a separate metering mechanism is provided. Such an arrangement is described in International Patent application No. WO 92/00771, which is incorporated herein by reference. Alternatively, if the medicament reservoir comprises unit dosage means, then the medicament reservoir and metering mechanism may comprise a single unit. Such an arrangement is described in European Patent No. 664 239, which is also incorporated herein by reference.

In the invention the inhaler may optionally include a conventionally known breath actuated mechanism. Thus, the counter mechanism of the invention may be actuated separately, simultaneously or sequentially with such breath actuated mechanism.

According to a yet further aspect of the invention we provide a method of treating a patient with a respiratory disorder which comprises administering a therapeutically effective amount of a medicament using an inhaler as hereinbefore described.

According to a further feature of the invention we provide a method of drug delivery to a patient which comprises administering a medicament to a patient suffering a respiratory disorder which comprises administering a therapeutically effective amount of a medicament using an inhaler as hereinbefore described.

The inhaler of the invention is advantageous in that, inter alia, it enables the delivery of dispersions of finely divided forms of medicament and avoids some if the disadvantageous of dosing experienced with some known DPIs. Thus, the inhaler of the invention may comprise a CLIC HALER, such as is described in International Patent application No. WO 92/00771. Alternatively, the inhaler of the invention may comprise a "double chimney" inhaler, such as is described in International Patent application No. WO 01/39823. Thus it should be understood that one advantage provided by the present invention is that a range of preselected dosages may be chosen by a patient within a single device.

A variety of medicaments may be administered by using the inhaler of the invention, such medicaments may have a systemic or non-systemic activity on the patient. Such medicaments are generally (but not limiting) antibiotics, bronchodilators or other anti-asthma drugs. Such medicaments include, but are not limited to β₂-agonists, e.g. fenoterol, formoterol, pirbuterol, reproterol, rimiterol, salbutamol, salmeterol and terbutaline; non-selective beta-stimulants such as isoprenaline; xanthine bronchodilators, e.g. theophylline, aminophylline and choline theophyllinate; anticholinergics, e.g. ipratropium bromide; mast cell stabilisers, e.g. sodium cromoglycate and ketotifen; bronchial anti-inflammatory agents, e.g. nedocromil sodium; and steroids, e.g. beclomethasone dipropionate, fluticasone, budesonide and flunisolide; and combinations thereof.

Specific combinations of medicaments which may be mentioned include combinations of steroids, such as, beclomethasone dipropionate, fluticasone, budesonide and flunisolide; and combinations of to β₂-agonists, such as, formoterol and salmeterol. It is also within the scope of this invention to include combinations of one or more of the aforementioned steroids with one or more of the aforementioned β₂-agonists.

Thus, according to a yet further feature of the invention we provide a method of treating a patient with a respiratory disorder which comprises administering a therapeutically effective amount of a medicament using an inhaler as hereinbefore described. Further medicaments which may be mentioned include systemically active materials, such as, proteinaceous compounds and/or macromolecules, for example, leuprolide and alpha interferon; growth factors, anticoagulants, immunomodulators, cytokines, nucleic acids, hormones, such as insulin human growth hormone and parathyroid hormone.

We also provide the use of an aerosol delivery device of the invention in the manufacture of an medicament delivery device as hereinbefore described.

It is within the scope of this invention to include combinations of any of the aforementioned medicaments.

The invention will now be described by way of example only and with reference to the accompanying drawings, in which; Figure 1 is a schematic representation of a dispensing cone with a small capacity metering member engaging the cog wheel;

Figure 2 is a schematic side view of a dispensing cone and a counter mechanism;

Figure 3 is a further representation of Figure 1;

Figure 4 is a schematic representation of the dispensing cone after dispensing a first dosage;

Figure 5 is schematic representation of a dispensing cone with a large capacity metering member engaging the cog wheel;

Figure 6 is a schematic representation of the dispensing cone after dispensing a first large dosage; and Figures 7-9 are schematic representations of the counter face moving from "full" to

"empty".

Referring to Figure 1, a dispensing system (1) comprises a metering member (2) in the form of a dispensing cone which comprises a frusto conical member. The conical surface (3) is provided with four equally spaced apart metering cups (4, 5, 6 and 7).

The metering cups (4, 5, 6 and 7) have differing, and increasing, capacities to each other. The dispensing cone (2) comprises a peripheral edge (8). The edge (8) is provided with engaging means (9) in the form of teeth (10). The teeth (10) being situated adjacent the metering cups (4, 5, 6 and 7) and the number of teeth (10) being dependent upon the size (capacity) of the metering cups (4, 5, 6 and 7). Thus, metering cup (4) is provided with one peripheral tooth (11), metering cup (5) is provided with two peripheral teeth (12), metering cup (6) is provided with three peripheral teeth (13) and metering cup (7) is provided with five peripheral teeth (14).

The dispensing system (1) is also provided with a counter face (15) which is operably linked to a cog wheel (16). The cog wheel (16) is operably linked to the counter face (15).

Referring to Figure 2, a dispensing cone (2) is provided with a ratchet wheel (20) which is adapted to engage with the cone (20) and the cog wheel (16) and thereby the counter face (15).

Referring to Figures 7 to 9, the counter face (15) is rotatable and comprises a viewing window (17) on its surface (18). The surface (18) is rotatable and comprises a viewing window (17) on its surface (18). The surface (18) is marked with a spiral indicator line (19).

Thus, in use, the dispensing cone (2) is rotated through, e.g. 45°, to dispense a dose of medicament. The rotation of the cone (2) causes the peripheral teeth (10) to engage with and rotate the cog wheel (16). Rotation of the cog wheel (16) causes the counter face (15) to rotate and the spiral indicator line (19) to rotate and effectively move within the viewing window (17). The two teeth (4) engage and therefore rotate the cog (16) and the counter face (15) rotates accordingly.

To select a different dosage the dispensing cone (2) may be disengaged from the cog (16) wheel and rotated until the desired dosage metering cup (4) is selected. When a higher dosage metering cup (7) is selected a greater number of teeth (10) engage the cog wheel (16). Thus when the dispensing cone (2) is actuated by being rotated through 45° the cog wheel (16) and the counter face (15) rotate accordingly.

Thus the spiral indicator hne (19), as seen through the viewing window (17), moves from, e.g. "full" to "empty".

Claims

1. A medicament delivery device which comprises a medicament reservoir, a metering member and a delivery channel characterised in that the metering member is adapted to deliver a preselected dosage of medicament from a range of dosages and the delivery device is provided with an indicator means for gauging the capacity of the medicament reservoir.

2. A medicament delivery device according to claim 1 characterised in that the indicator means is adapted to be moved from a first position each time that the metering member dispenses a dosage of medicament to a second position and wherein means is provided to indicate the dosage removed and/or the remaining capacity of the reservoir.

3. A medicament delivery device according to claim 2 characterised in that the indicator is in a first position when the metering member is in a metering position and the indicator is in a second position when the metering member is in a dispensing position.

4. A medicament delivery device according to claim 1 characterised in that the metering member is provided with engaging means which is adapted to engage either directly or indirectly with the indicator.

5. A medicament delivery device according to claim 4 characterised in that the metering member is adapted to disengage from the indicator after the medicament has been dispensed.

6. A medicament delivery device according to claim 1 characterised in that the size of the engaging means can very depending on the capacity of the metering cup.

7. A medicament delivery device according to claim 4 characterised in that the metering member engaging means engages with indicator engaging means and moves the indicator to a greater or lesser degree depending upon the capacity of the metering member used.

8. A medicament delivery device according to claim 2 characterised in that the metering member engaging means comprises a toothed member.

9. A medicament delivery device according to claim 4 characterised in that the indicator engaging means comprises a toothed wheel.

10. A medicament delivery device according to claim 9 characterised in that the metering member comprises one or more teeth adapted to engage the cog.

11. A medicament delivery device according to claim 9 characterised in that the number of teeth provided to the metering may vary depending upon the capacity of the metering member.

12. A medicament delivery device according to claim 11 characterised in that the metering member is provided with 1 tooth for every 10 μg of capacity.

13. A medicament delivery device according to claim 11 characterised in that the metering member is provided with one tooth for each 100 μg of capacity.

14. A medicament delivery device according to claim 1 characterised in that the device is an oral delivery device.

15. A medicament delivery device according to claim 14 characterised in that the device is an inhaler.

16. A medicament delivery device according to claim 15 characterised in that the inhaler is a DPI.

17. A medicament delivery device according to claim 15 characterised in that the inhaler includes a breath actuated mechanism.

18. A medicament delivery device according to claim 17 characterised in that the gauging mechanism is actuated separately, simultaneously or sequentially with the breath actuated mechanism.

19. A medicament delivery device according to claim 1 characterised in that the medicament is selected from the group, antibiotics, bronchodilators, anti-asthma drugs, such as β₂-agonists; fenoterol, formoterol, pirbuterol, reproterol, rimiterol, salbutamol, salmeterol and terbutaline; non-selective beta-stimulants such as isoprenaline; xanthine bronchodilators; theophylline, aminophylline and choline theophyllinate; anticholinergics such as ipratropium bromide; mast cell stabilisers, such as sodium cromoglycate and ketotifen; bronchial anti-inflammatory agents, such as nedocromil sodium; steroids, such as beclomethasone dipropionate, fluticasone, budesonide and flunisolide; and combinations thereof.

20. A medicament delivery device according to claim 19 characterised in that the combination of medicaments is selected from steroids, such as beclomethasone dipropionate, fluticasone, budesonide and flunisolide; and combinations of to β - agonists, such as, formoterol and salmeterol.

21. A medicament delivery device according to claim 1 characterised in that the medicament is systemically active.

22. A medicament delivery device according to claim 20 characterised in that the medicament is selected from a proteinaceous compound and/or macromolecules, such as hormones and mediators, such as insulin, human growth hormone, leuprolide and alpha interferon; growth factors, anticoagulants, immunomodulators, cytokines and nucleic acids.

23. A medicament delivery device according to claim 1 characterised in that the medicament is a combination selected from a medicament as defined in claim 18 and a medicament as defined in claim 19.

24. A method of administering a medicament which comprises the use of a medicament delivery device according to claim 1.

25. A method of treatment of a patient which comprises the administration of a medicament using an inhaler according to claiml5.

26. A method according to claim 25 characterised in that the disorder is a respiratory disorder.

27. A method of treatment of a patient with a systemic disorder which comprises the administration of a medicament using an inhaler according to claim 15.

28. A delivery device or a method substantially as described with reference to the accompanying examples and drawings.