[0001] This invention relates to an indicator apparatus and method for determining at least an approximate fill level, or remaining fill, of a metered dose inhaler (MDI), or, more specifically, of the metered dose inhaler canister.

BACKGROUND

[0002] Metered-dose inhalers (MDIs) are medication delivery devices that can deliver a pharmaceutical formulation including one or more pharmaceutically active compounds ("active ingredients") to a human or other mammalian patient.

[0003] Typically the pharmaceutical formulation is delivered by the MDI as unit doses in the form of an aerosol. Each actuation of the MDI delivers one unit dose. The unit dose is expelled by the MDI and can be taken into the body of the patient on inhalation, via the nose or mouth. The pharmaceutical formulation can be delivered to or via the respiratory tract, notably to the lungs, of the patient on inhalation.

[0004] The MDI includes a metering valve which is configured to ensure that each dose of the pharmaceutical formulation expelled by the MDI is the same, within permitted tolerances. In particular, each dose should include the same amount of the active ingredient(s). Generally, the metering valve is configured to dispense a constant volume of the pharmaceutical formulation on each actuation of the MDI.

[0005] Metered-dose inhalers are typically used for the treatment of respiratory infections and disorders including respiratory tract infections, obstructive lung disease, inflammatory lung disease and chronic obstructive pulmonary disease. Asthma treatment is a particularly common use of MDIs.

[0006] MDIs may be used to deliver various types of active ingredients as appropriate to the medical condition of the patient being treated including, by way of example, bronchodilators (β ₂ agonists and anticholinergics) and corticosteroids.

[0007] A metered-dose inhaler typically includes a canister and an actuator housing. The canister is a closed vessel provided with a metering valve and which in use contains a pharmaceutical (therapeutic) formulation, which generally includes one or more active ingredients and propellant such as a liquefied gas propellant. The formulation may also include various other components, such as stabilizing excipients.

[0008] A typical MDI canister can comprise a cylindrical body portion having a base wall at one end. An end of the cylindrical body portion distal from the base wall can include a neck in which is mounted a metering valve. The body portion and neck can be made from aluminium or steel, typically by deep drawing. The metering valve can include a valve stem extending outwardly from the canister through which valve stem the pharmaceutical formulation is dispensed.

[0009] The canister may be positioned in an actuator housing, which may typically include an approximately cylindrical body portion into which the canister is received and a discharge nozzle or sleeve, often called a "valve stem block" which communicates with a discharge opening. The discharge opening may be a mouthpiece opening or nosepiece opening, as appropriate to the delivery mode and is configured accordingly. When the canister is fully received in the body portion to achieve its operational configuration, a portion of the length of the valve stem of the metering valve is received in the discharge sleeve.

[0010] For actuation of the MDI to dispense the unit dose, the user presses the base of the canister to urge the canister forwardly into the actuator housing which causes the valve stem to be depressed partially into the container. This depression of the valve stem results in the discharge of the unit dose of the pharmaceutical formulation through the valve stem and the discharge sleeve and consequently through the discharge opening for delivery to the patient. On release of the canister by the user, the valve stem is biased to return to its initial position.

[0011] A metered-dose inhaler contains enough of the pharmaceutical formulation in the canister for a certain number of actuations, equating to a certain number of unit doses. The number of doses is determined by the supplier of the MDI to ensure that for each actuation of the MDI within that number of doses, the patient consistently receives the same unit dose of the pharmaceutical active. However, the inhaler may continue to operate after the determined number of actuations has been reached. This carries the significant risk that for such "excess" actuations, the amount of pharmaceutical active being delivered to the patient may not be correct and in particular may be insufficient. Many patients (notably children and the elderly) can find it very difficult (and in practical terms can find it impossible) accurately to maintain an on-going count of the number of actuations (and thus the number of doses) used or delivered in order to ensure that the determined number of doses is not exceeded.

[0012] Although efforts have been made to provide mechanical dose counters, these dose counters can add significant cost and materials to the device and can be inaccurate. Mechanical dose counters may not be able to differentiate events when a dose is actually delivered as compared with other events, such as when a metered-dose inhaler is dropped on the ground or otherwise experiences movement that does not press the metering valve sufficiently for a dose to be delivered. Hence mechanical dose counters have not gained widespread acceptance from healthcare providers.

[0013] Electro-mechanical and electronic dose counters have also been proposed but have yet to achieve a sufficiently low cost and sufficiently high reliability. In particular, the problem of false counts (such us when the MDI is accidentally dropped) has not been resolved and difficulties persist and providing a power source which is suitably compact and cheap and which can reliably provide power throughout the full service life of the MDI.

[0014] Embodiments of the invention seek to provide an alternative to mechanical or electrical dose counters by which a user can determine, at least to a reasonable approximation, the quantity of pharmaceutical formulation (which equates to the number of doses) remaining in the canister of a metered dose inhaler. Embodiments of the invention can also provide a user with an indication that the pharmaceutical formulation in the canister of a metered dose inhaler is approaching exhaustion, that is, the quantity of the pharmaceutical formulation within the canister has reached a level at which the canister (or the whole MDI) will shortly need to be replaced. In accordance with some preferred embodiments, the said quantity is determined by an apparatus which can be one or more of: inexpensive, mechanically uncomplicated, robust and easy for a patient or other person to operate.

BRIEF SUMMARY OF THE DISCLOSURE

[0015] In accordance with a first aspect of the present invention there is provided an apparatus for determining a quantity of a pharmaceutical formulation in a metered dose inhaler canister, the apparatus comprising:

a support assembly including a support element and a canister receiving element supported by the support element, said support assembly defining a pivot about which the canister receiving element is free to pivot with respect to the support element,

a biasing element of said support assembly configured such that the centre of gravity of the canister receiving element is not coincident with the pivot, and

a measurement component configured for determining a rest angle of said canister receiving element with the canister received therein when supported by the support element.

[0016] In some preferred embodiments the canister receiving element can comprise a metered dose inhaler actuator housing in which the canister is received.

[0017] In some preferred embodiments the metered dose inhaler actuator housing can be separable by a user from the support element and replaceable by the user in or on the support element. Such separation and replacement can be without damage to, or alteration of the functional capability of, the said housing or support element.

[0018] In some preferred embodiments the canister receiving element with the canister received therein can pivot about a substantially horizontal axis.

[0019] In some preferred embodiments the support element can include a pivot rod or bar and the actuator housing can include a mounting formation configured to receive at least a portion of said pivot rod or bar such that the canister receiving element pivots about said pivot rod or bar.

[0020] In some preferred embodiments said formation can comprises a bore formed integrally with the actuator housing.

[0021] In some preferred embodiments , when the canister receiving element is supported by the support element, said pivot rod or bar can be arranged substantially perpendicular to a longitudinal axis of said canister when received in said canister receiving element.

[0022] In some preferred embodiments the actuator housing can include a pivot rod or bar and the support element can include at least one mounting formation configured to support at least a portion of said pivot rod or bar such that the canister receiving element pivots about the longitudinal axis of said pivot rod or bar.

[0023] In some preferred embodiments said measurement component can include a graphical, alphabetical or numerical scale arranged adjacent to the canister receiving element.

[0024] In some preferred embodiments the measurement component can pivot about the pivot of the support assembly.

[0025] In some preferred embodiments

the canister receiving element can comprise a base wall portion, at least one canister retaining formation extending at a first side of said base wall portion and a stabilising portion arranged at an opposed second side of said base wall portion, said base wall portion comprising at said second side a concave surface

the support element can comprise an upstanding bar or rod having an upper end, the canister receiving element can be mounted on said bar or rod with said concave surface in contacting relation with said bar or rod upper end, and

the stabilising portion can be configured such that the centre of gravity of the canister receiving element is below said upper end of the bar or rod. [0026] In some preferred embodiments said stabilising portion can comprise a skirt portion extending downwardly from said base wall.

[0027] In some preferred embodiments said biasing element can be mounted to, or integral with, said skirt portion. [0028] In some preferred embodiments said measurement component can includes a graphical, alphabetical or numerical scale arranged adjacent to the canister receiving element in fixed relation to the upright bar or rod.

[0029] According to a second aspect of the present invention there is provided a method of determining a quantity of a pharmaceutical formulation in a metered dose inhaler canister, the method comprising:

pivotaly supporting a canister receiving element in which said metered dose inhaler canister is retained on a pivot of a support element to form a support assembly comprising the canister receiving element and the support element, the support assembly including a biasing element configured such that the centre of gravity of the canister receiving element is not coincident with the pivot,

allowing the canister receiving element to pivot freely about said pivot

allowing the canister receiving element to achieve a rest position,

determining, at least approximately, a quantity of a pharmaceutical formulation in a metered dose inhaler canister on the basis of said rest angle.

BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Embodiments of the invention are further described hereinafter with reference to the accompanying drawings, in which:

Figures 1A, 1 B and 1 C show respectively an apparatus according to one embodiment of the invention where the canister contains different amounts of

pharmaceutical formulation. In Figure 1 A, the canister contains the highest amount of pharmaceutical formulation, in Figure 1 C the canister contains the lowest amount of pharmaceutical formulation and in Figure 1 B the canister contains an amount of pharmaceutical formulation intermediate that of the canister in Figures 1A and 1 C;

Figures 2A and 2B show an apparatus according to another embodiment of the invention;

Figure 3 shows an apparatus according to still another embodiment of the invention;

Figures 4A to 4C show respective parts of an apparatus according to a yet further embodiment of the invention and Figure 4D shows that apparatus in assembled form; Figures 5A to 5D show the apparatus of Figure 4D where the canister contains different amounts of pharmaceutical formulation. In Figure 5D, the canister contains the highest amount of pharmaceutical formulation, in Figure 5A the canister is empty or substantially empty, in Figure 5C the canister contains a lesser amount of pharmaceutical formulation than the canister of Figure 5D and in Figure 5B the canister contains a lesser amount of pharmaceutical formulation than the canister in Figure 5C;

Figure 5E shows a measurement component suitable for use with the apparatus of Figures 4A to 4D and 5A to 5D and

Figure 6 is an exploded view of a typical metered dose inhaler canister and actuator housing for oral drug delivery.

DETAILED DESCRIPTION

[0031] Referring initially to Figure 6 which shows in exploded view by way of general example a typical representation of a metered dose inhaler canister 912 and an actuator housing 914 configured for oral drug administration, as known in the art. The canister 912 can comprise a side wall 912A and a base wall 912B which together define a substantially cylindrical internal void in which a pharmaceutical formulation can be contained. An end of the canister 912 opposite to the base wall 912B can include a neck 912C in which is retained a metering valve. A valve stem 912D of the valve extends outwardly from the canister.

[0032] The actuator housing 914can include a body portion 914A and a mouthpiece 914M. The canister 912 is received into a void 914V of the actuator hosing which is shaped to retain the canister 912. The void 914V can be approximately cylindrical. Body portion can also be approximately cylindrical, but can take other forms. For example the body portion 914A can have a front face 914F which is relatively flatter than the remainder of the body portion 914R. Actuator housing 914 can further include a discharge nozzle or sleeve 914D, often called a "valve stem block" which communicates with a discharge opening 914P. The discharge opening can be in a mouthpiece 914M opening. When the canister 912 is fully received in the body portion to achieve its operational configuration, a portion of the length of the valve stem 912D of the metering valve can be received in the discharge sleeve 914D.

[0033] to Figures 1A, 1 B and 1C an apparatus 10 according to an embodiment of the invention includes a support assembly 11 comprising a support element in the form of a handle 16 and a canister receiving element in the form of an actuator housing 14. A canister 12 is, in use of the apparatus 10, received within the actuator housing 14. Canister 12 can be received into a body portion 12B of the actuator housing in

conventional manner.

[0034] Actuator housing 14 can advantageously be functionally (in terms of metered dosing of pharmaceutical formulation) and, in most respects, structurally similar to actuator housings of conventional metered dose inhalers. It is not, however, an essential requirement of the invention that the actuator housing is either functionally or structurally similar to such conventional actuator housings.

[0035] Thus, in a typical arrangement the actuator housing can include a body portion into which the canister 12 is received and a discharge nozzle or sleeve, often called a "valve stem block" which communicates with a discharge opening. The discharge opening can be in a mouthpiece opening 14M (shown in Figure 1 with a closure cap in place) or nosepiece opening, as appropriate to the delivery mode and is configured accordingly. When the canister is fully received in the body portion to achieve its operational configuration, a portion of the length of the valve stem of the metering valve can be received in the discharge sleeve.

[0036] In some preferred embodiments the actuator housing 14 can be configured to cooperate in a conventional manner with a metered dose inhaler canister, so that the MDI operates to deliver a metered dose of pharmaceutical formulation in a way familiar to patients. The canister 12 can be of conventional construction, as commonly used in metered dose inhalers, such as that described in relation to Figure 6. Thus in some preferred embodiments a typical MDI canister suitable for use with the apparatus of the invention can comprise a cylindrical body portion having a base wall at one end. An end of the cylindrical body portion distal from the base wall can include a neck in which is mounted a metering valve. In some preferred embodiments, the body portion and neck can be made from aluminium or steel, typically by deep drawing. Other materials for forming the canister are not excluded, provided that the canister formed from such other materials can meet regulatory requirements for pharmaceutical products and devices. The metering valve can include a valve stem extending outwardly from the canister through which valve stem the pharmaceutical formulation is dispensed.

[0037] The actuator housing 14 of Figures 1A, 1 B and 1C differs from a conventional actuator housing in additionally including a pivot structure 18 about which the actuator housing including the canister 12 can pivot. The selection of an appropriate pivot structure is not particularly constrained provided that the actuator housing can pivot freely in order for a measurement to be made of the quantity of pharmaceutical formulation contained in the canister, as further described below. [0038] As shown in the illustrated embodiment, the actuator housing 14 can include an upstanding portion such as a wall 22 which can define a bore or passage. The bore or passage can be a through bore or passage or a blind bore or passage. In variations, two co-linear bores or passages can be provided, the respective openings of which are at opposed sides of upstanding portion 22.

[0039] The said bore or passage can receive a pivot rod or bar 18R about which the actuator housing 14 can pivot. The pivot rod or bar 18R can be a single pivot rod or bar, or can be in the form of discrete pivot rod portions, each respective pivot rod portion being received in the bore or passage from a respective end thereof, or, in the case of the co- linear bores noted above, each respective pivot rod portion can be received in a respective co-linear bore or passage.

[0040] The pivot rod or bar 18R can be attached to the handle 16. In some

embodiments, the pivot rod or bar 18R can be formed integrally with the handle 16.

Handle 16 can be grasped in a user's hand or fingers so that the actuator housing is suspended from the handle 16 via the pivot rod or bar 18R. Since the actuator housing 14 can pivot on pivot rod or bar 18R, the actuator housing 14 with the canister 12 therein can move about the pivot until it adopts a stationary or rest condition. In the rest condition, the centre of gravity of the actuator housing 14 with the canister 12 therein lies in a vertical plane which includes the pivot axis. The actuator housing is configured (such as by the choice of location of the pivot) so that the centre of gravity of the actuator housing 14 with the canister 12 received therein is not coincident with the pivot. In many constructions, no special or complex measures are required in order to achieve the condition that the centre of gravity of the actuator housing 14 with the canister 12 received therein is not coincident with the pivot since this can simply be an inherent characteristic of the shape and construction of the actuator housing 14. Hence a biasing element to achieve this condition can be an inherent or intrinsic property or characteristic of the actuator housing 14 arising from the particular construction of the actuator housing 14. If required, however, a separate biasing element can be applied to or included within the actuator housing. In one example, the biasing element can be a weight.

[0041] One preferred location of the pivot, as illustrated in Figures 1A to 1C can be at a front side of the body portion 14B of the actuator housing 14, that is, at the same side as dispensing outlet (e.g. mouthpiece) 14M. Other locations for the pivot are possible, such as at the "heel" 14H of the actuator housing, accepting that with the pivot in such a location a retaining component or device could be needed to retain the canister 12 in the actuator housing against the action of gravity. [0042] In one preferred arrangement the pivot rod or bar 18R (or the respective pivot rod portions) is (are) arranged to be perpendicular to, and, in some embodiments, non- intersecting with, a longitudinal axis 24 of the canister 12 when the canister is received in the actuator housing 14. In some particularly preferred arrangements, the pivot rod or bar 18R (or the respective pivot rod portions) is (are) arranged to be substantially parallel to a tangent to the side wall 12S of the canister 12 when the canister is received in the actuator housing 14.

[0043] In one convenient arrangement, and as illustrated in Figures 1A to 1C, the handle 16 can be formed integrally with the pivot rod or bar 18R (or the respective pivot rod portions). Conveniently, the handle 16 can be formed from a relatively stiff wire which can be shaped by bending, such as at corner 16C.

[0044] If required, handle 16 can be separated from the actuator housing 14, such as by deflection or resilient deformation of the handle 16 until the pivot rod or bar 18R (or the respective pivot rod portions) is (are) displaced from the bore or passage. Removal of the handle 16 can be advantageous to facilitate normal use of the MDI, that is, for dispensing medicament (the pharmaceutical formulation) to a patient. The handle can subsequently be replaced in similar manner. Removal and replacement of the handle can be effected multiple times without damage to, or modification of, the actuator housing 14 or the handle 16.

[0045] In some preferred embodiments of the invention, apparatus 10 can be provided with an attached or integral measurement component configured for determining a rest angle of the canister receiving element with the canister received therein. The

measurement component can be attached to or integral with the support element or the canister receiving element. In other preferred embodiments, the measurement component can be provided separately from the support element or the canister receiving element. In some preferred embodiments, the measurement component can be a numerical, alphabetical, alphanumeric or graphical scale or indicator.

[0046] The said scale or indicator can provide a user with information as to the angle of inclination of the canister receiving element with the canister received therein when in its rest position, that is, the rest angle of the canister receiving element with the canister received therein. The rest position is achieved when the canister receiving element with the canister received therein is supported by the support component and allowed to pivot freely until it freely adopts a stationary position, which is the rest position.

[0047] Noting that the centre of gravity of the canister receiving element with the canister received therein is not coincident with the pivot, the rest position of the canister receiving element with the canister received therein is dependent on the quantity of the pharmaceutical formulation (remaining) in the canister. The rest position is achieved when the centre of gravity of the canister receiving element with the canister received therein is below the pivot and in the vertical plane containing the pivot axis. The position of the centre of gravity of the canister receiving element with the canister received therein changes with changes in the quantity of the pharmaceutical formulation contained in the canister 12. It follows that a different position of the centre of gravity leads to a different rest angle. Thus by using the scale or indicator to assess the angle of the canister receiving element with the canister received therein in its rest position, the user is provided with information relating to the quantity of the pharmaceutical formulation in the canister.

[0048] Figures 1 A, 1 B and 1 C are illustrative of this effect. In Figure 1 A, the canister 12 contains a relatively higher amount of pharmaceutical formulation, such as for example about 15ml. In Figure 1 B, the canister 12 contains a lesser amount of pharmaceutical formulation, such as for example about 10ml. Comparison of Figures 1A and 1 B shows that the actuator housing 14 with the canister 12 received therein adopts different rest positions. In Figure 1A, the angle of inclination of the actuator housing 14 with respect to the vertical is greater than the angle of inclination of the actuator housing 14 in Figure 1 B, reflecting the lesser amount of pharmaceutical formulation contained in the canister 12 of Figure 1 B. Similarly, comparison of Figures 1 B and 1C shows that the actuator housing 14 with the canister 12 received therein adopts different rest positions. In Figure 1 B, the angle of inclination of the actuator housing 14 with respect to the vertical is greater than the angle of inclination of the actuator housing 14 in Figure 1 C, reflecting the lesser amount of pharmaceutical formulation contained in the canister 12 of Figure 1C.

[0049] The scale or indicator 20 is, in some preferred embodiments, mounted or positioned to adopt a consistent position (which position can be an angular position) for each angular measurement of the canister receiving element with the canister received therein. In this way consistency between successive measurements can be achieved.

[0050] In some preferred embodiments, the scale or indicator 20 is mounted or positioned immediately adjacent the canister receiving element with the canister received therein, in particular, immediately adjacent the actuator housing 14. The user can then make a consistent comparison between a part of the canister receiving element with the canister received therein (in particular the actuator housing 14) and the scale or indicator. In the embodiment illustrated in Figures 1A to 1 C the user can make a comparison between the scale or indicator and an adjacent generally linear part of the actuator housing 14. Such linear part can be a part of the approximately cylindrical body portion 14B, in particular of a front potion (that is, at the same side as dispensing outlet 14M) of the actuator housing 14. In other configurations, scale or indicator 20 can be positioned so that a comparison can be made by a user between the scale or indicator 20 and a generally linear part of a rear potion (that is, at the same side as heel 14H) of the actuator housing 14.

[0051] In some preferred arrangements the scale or indicator 20 can be attached to the support element (e.g. handle) 16 and in other arrangements the scale or indicator 20 can be attached to the canister receiving element (e.g. actuator housing) 14. Where the scale or indicator 20 is attached to the canister receiving element (e.g. actuator housing) 14, the scale 20 can be freely moveable with respect to the canister receiving element. Where the scale or indicator 20 is attached to the canister receiving element (e.g. actuator housing) 14, preferably the scale or indicator 20 is removable from said canister receiving element 14 to facilitate normal use of the MDI and subsequently re-attachable to the canister receiving element. The steps of removal and re-attachment of the scale or indicator 20 can be performed multiple times without damage to, or modification of, the scale or indicator 20 or the support assembly 11.

[0052] In some preferred arrangements the scale or indicator 20 is pivotal ly attached to the support element 16.

[0053] In some preferred arrangements, scale or indicator 20 can pivot about the same pivot axis as the canister receiving element. Desirably, the scale or indicator 20 can in effect hang freely from the pivot axis. Conveniently the scale or indicator 20 can hang freely from the pivot bar or rod 18R. Thus when a measurement is to be taken from the scale or indicator 20, the scale of indicator 20 consistently can adopt its own rest condition, which is always the same between successive measurements. More particularly the scale or indicator 20 is not then influenced or affected by the angular position about the pivot axis of the canister receiving element 14 or of the support element (handle) 16.

[0054] As noted, measurement component 20 can be a scale or indicator which can be graphical, alphabetical or numerical, or a mixture of these. A graphical scale is illustrated in Figures 1A to 1 C. In these Figures, measurement component 20 comprises a substrate which is preferably substantially planar. The substrate is divided into zones 20-1 , 20-2 and 20-3 which are visually differentiated such as by having different shading and/or different colouring. For example, zone 20-1 can be coloured in a green colour, zone 20-2 can be coloured in an orange colour and zone 20-3 can be coloured in a red colour. When the canister has a fill of the pharmaceutical formulation at or near to its as-manufactured fill level, the scale 20 can be configured so that the actuator housing 14 with the canister 12 received therein is, in the rest position, adjacent to the green zone 20-1. A user can thus be confident that the canister 12 contains a good supply of pharmaceutical formulation, sufficient for delivering a relatively high number of doses. Such a condition is illustrated in Figure 1A. When the canister has a fill of the pharmaceutical formulation which is reduced (by virtue of successive actuations or the MDI) to - for example - about half its as- manufactured fill level, the scale 20 can be configured so that the actuator housing 14 with the canister 12 received therein is, in the rest position, adjacent to the orange zone 20-2. A user can thus be confident that the canister 12 contains a good supply of pharmaceutical formulation, sufficient for delivering a moderate number of doses but is warned that the MDI may need replacing relatively soon. Such a condition is illustrated in Figure 1 B.

When the canister has a fill of the pharmaceutical formulation which is reduced (by virtue of successive actuations of the MDI) to - for example - about one third or one quarter or less than its as-manufactured fill level, the scale 20 can be configured so that the actuator housing 14 with the canister 12 received therein is, in the rest position, adjacent to the red zone 20-3. A user can thus be advised that the canister 12 contains a limited supply of pharmaceutical formulation, sufficient for delivering a relatively small number of doses and is warned that the MDI will need replacing within a short time period. Such a condition is illustrated in Figure 1C.

[0055] Use of the apparatus of the invention can be simple for many patients, including those who may suffer a physical impairment. Firstly, the user fits the support element 16 to the canister receiving element 14, if not already so fitted. More specifically with reference to the embodiment of Figures 1A to 1 C, the user fits the handle 16 to the actuator housing 14. Generally, the canister 12 will already be in the actuator housing 14, but if not, the user places the canister 12 in the actuator housing. The user then suspends the canister receiving element 14 by the handle 16 so that the canister receiving element 14 is not in contact with any other surface or structure and is therefore free to move about its pivot. Most preferably, the user should take care to suspend the canister receiving element 14 so that the pivot axis is held substantially horizontally. The canister receiving element with the canister received thereon can thus settle to its rest position, at which time the user can take a reading from the scale or indicator 20.

[0056] It is noted that it is not a primary objective of embodiments of the present invention to provide a user with a fully quantitative measure of the number of doses remaining in the canister 12. That is, the user does not need to determine an exact quantity of the pharmaceutical formulation in the canister. Rather, embodiments of the present invention seek to provide the user with a more general indication as to the remaining quantity of the pharmaceutical formulation in the canister and to give the user adequate advanced warning if such quantity is low. The user can then take appropriate steps to replace the MDI, or to carry a spare MDI which is available to use when

(according to the manufacturer's recommendations) the first MDI is exhausted. [0057] An alternative embodiment of an apparatus according to the invention is illustrated with reference to Figures 2A and 2B. The apparatus 210 of Figures 2A and 2B is similar in its principles of operation to that of Figures 1A to 1 C and corresponding parts are given the same reference numbers, except for the addition of the prefix "2". By way of example, the canister numbered 12 in Figures 1 A-C is numbered as canister 212 in Figures 2A and 2B.

[0058] Referring now to Figures 2A and 2B, the support element 216 in the illustrated embodiment can cooperate with a supporting element or fixture in order to achieve a stable supporting position. In some preferred embodiments the support element can comprise a stand or the like configured to stand or rest on a generally horizontal supporting surface 204 such as a table, shelf, worktop or the like. In the illustrated embodiment stand 216 is represented by a simple box, but in other embodiments more robust and/or aesthetically pleasing constructions for stand 216 can be used. In some preferred embodiments, the support element 216 functions primarily to provide a stable support for a pivot rod or bar 218R to which a canister receiving element 214 can be pivotally mounted. The pivot rod or bar 218R can be mounted at a first end 218RM in fixed relation to the stand 216 can and extend outwardly from the stand 216 to an opposed free end 218RX. In some preferred embodiments, pivot rod or bar 218R is arranged substantially horizontally. In some preferred embodiments, the stand support element 216 can be configured such that when the support element 216 cooperates with the supporting element of fixture, the pivot rod or bar 218R is arranged substantially horizontally. More especially, the stand 216 can be configured such that when the stand 216 is arranged on a substantially horizontal surface 204, the pivot rod or bar 218R extends substantially horizontally from the stand 216.

[0059] Embodiments of the apparatus 210 can further include a measurement component which is typically and conveniently in the form of a scale or indicator 220. Scale or indicator 220 can be fixedly mounted to (e.g. affixed to) the stand 216. In some preferred embodiments, however, the scale or indicator 220 can be pivotally mounted to the stand 216. Advantageously, the scale or indicator 220 can be arranged to hang from a pivot support 218S which can be pivot rod or bar 218R. Desirably, the scale or indicator 220 can pivot about the same pivot axis as the canister receiving element.

[0060] Embodiments of the apparatus 210 further include a canister receiving element 214 which can be of similar construction to canister receiving element 14 of Figures 1A to 1 C. In particular, canister receiving element can be an actuator housing 214 of a metered dose inhaler. Actuator housing 214 can preferably be functionally (in terms of metered dosing of pharmaceutical formulation) and, in most respects, structurally similar to actuator housings of conventional metered dose inhalers. It is not, however, an essential requirement of the invention that the actuator housing 214 is either functionally or structurally similar to such conventional actuator housings.

[0061] In some preferred embodiments however the actuator housing 214 can be configured to cooperate with a conventional metered dose inhaler canister (such as the canister 14 discussed in relation to Figure 6), so that the MDI operates in a way familiar to patients. Thus in typical arrangements according to this embodiment, canister receiving element 214 can in most respects be the same as a conventional and widely known metered dose inhaler actuator housing, with the additional inclusion of mounting means suitable to allow the actuator housing 214 to be pivotally mounted to the pivot bar or rod 218R. Preferably such means can be configured such that the actuator housing 214 is pivotally suspended from the pivot bar or rod 218R. In some embodiments, such mounting means can be, for example, one or more hooks, loops or eyes mounted to the actuator housing 214 which can receive or otherwise pivotally engage the pivot bar or rod 218R.

[0062] In some preferred configurations the mounting means can comprise one or more passages or bores into which the pivot bar or rod 218R can be received. A single bore or passage can be a through bore or passage or a blind bore or passage. A blind bore or passage can be advantageous for ensuring that the actuator housing 214 can be mounted to the pivot bar or rod 218R in only one orientation. In variations, two or more co-linear bores or passages can be provided, into each of which the pivot rod or bar 218R can be received. In some preferred embodiments, the actuator housing 14 can include an upstanding portion such as a wall 222 which can define the one or more bores or passages.

[0063] Thus the passage(s) or bore(s) 222 can define with the pivot bar or rod 218R the pivot about which the actuator housing 214 can freely rotate. One preferred location of the passage(s) or bore(s), as illustrated in Figure 2B can be at a front side of the

approximately cylindrical body portion 214B of the actuator housing 214, that is, at the same side as dispensing outlet (e.g. mouthpiece) 214M. Other locations for the passage(s) or bore(s) are possible, such as at the "heel" 214H of the actuator housing, accepting that with the pivot in such a location a retaining component or device could be needed to retain the canister 212 in the actuator housing 214 against the action of gravity.

[0064] In one preferred arrangement, when received into the bore(s) or passage(s) of the actuator housing 214, the pivot rod or bar 218R is arranged to be perpendicular to, and, in some arrangements, non-intersecting with, a longitudinal axis 224 of the canister 212 when the canister is received in the actuator housing 214. In some particularly preferred arrangements, the pivot rod or bar 218R is arranged to be substantially parallel to a tangent to the side wall 212S of the canister 212.

[0065] Actuator housing 214 can be mounted to the pivot rod or bar 218R (by insertion of the pivot rod or bar 218R into the above-mentioned bore or passage) and correspondingly removed therefrom multiple times as required by the user. Such removal and re-mounting can be achieved without modification of, or damage to, the actuator housing 214 or the pivot rod or bar 218R. It can be expected that a user will mount the actuator housing 214 to the pivot rod or bar 218R only when the user desires to make a measurement of the remaining contents of the MDI.

[0066] The manner in which a user can make a measurement of the (remaining) contents of the canister 212 is in its general principles the same as that of the embodiment described in relation to Figures 1A to 1 C. Thus, use of the apparatus 210 of this embodiment can also be simple for many patients, including those who may suffer a physical impairment. Firstly, the user mounts the canister receiving element 214 to the support element 216 to (if not already so mounted). More specifically with reference to the embodiment of Figure 2B, the user mounts the actuator housing 214 to the pivot bar or rod 218R. Generally, the canister 212 will already be in the actuator housing 214, but if not, the user places the canister 212 in the actuator housing. The canister receiving element 214 is thus suspended from the pivot rod or bar 218R so that the canister receiving element 214 (actuator housing 214) is not in contact with any other surface or structure and is therefore free to move about its pivot. In preferred configurations the construction of the stand 216 is such that when the canister receiving element 14 is mounted to the pivot rod or bar 218R the pivot axis is substantially horizontal. In practical terms, the pivot rod or bar 218R can be arranged to be nominally horizontal. Some variation from the horizontal can be acceptable if, for example, the surface on which the stand 216 rests itself varies to some small extent from the horizontal. The canister receiving element 214 with the canister received therein can thus settle to its rest position, at which time the user can take a reading from the scale or indicator 220 in a manner corresponding to that described above in relation to Figures 1A to 1 C. It is noted in this respect that the pivotal suspension of the scale or indicator 220, in accordance with some embodiments of the invention, can be advantageous in ensuring consistency between successive measurements. Thus by pivotally suspending both the scale or indicator 220 and the canister receiving element with the canister therein, both achieve a consistent rest position irrespective of variations in an angle of inclination of the stand 216 such a might be caused if the stand 216 rests on a surface which is not completely horizontal. [0067] Another alternative embodiment of an apparatus according to the invention is illustrated with reference to Figure 3. The apparatus 310 of Figure is similar in its principles of operation to that of Figures 1A to 1 C and 2A and 2B and corresponding parts are given the same reference numbers, except for the addition of the prefix "3". By way of example, the canister numbered 12 of Figure 1A-C is numbered as canister 312 in Figure 3.

[0068] Referring now to Figure 3, apparatus 310 according to an embodiment of the invention includes a support assembly 311 comprising a support element 316 which can be in the form of a stand and a canister receiving element 314 which can be in the form of an actuator housing. The canister receiving element 314 with the canister 312 received therein is pivotally suspended at pivot structure 318 from the support element 316. The actuator housing 314 can be of generally conventional type as discussed in relation to the embodiments above. Support element 316 can be in the form of a stand having a base portion 316B configured to rest stably on a generally horizontal supporting surface such as a table, shelf, worktop or the like. Extending upwardly (with respect to the orientation of the stand in use, as shown for example in Figure 3) from base portion 316B is at least one upright portion 3161).

[0069] Depending from at least one upright 316U is a pivot bar or rod 318R which, for pivotally attaching the stand 316 to the actuator housing 314, can enter a bore or passage formed in the actuator housing in substantially the same manner as described above in relation to pivot bars or rods 18R and 218R. A single upright 316U can be sufficient, but where two uprights 316U are provided each may include an oppositely directed pivot bar or rod 318R configured to enter opposite ends of the same bore or passage, or alternatively, two co-linear bores or passages can be provided with oppositely arranged openings each such bore or passage receiving the pivot rod or bar of a respective upright 316U. In preferred constructions, the bore or passage (or the bores or passages) and the pivot rod(s) or bar(s) 318R are arranged substantially horizontally when the stand is supported on a substantially horizontal surface, so that the actuator housing 314 can pivot about a substantially horizontal axis.

[0070] If required, stand 316 can be separated from the actuator housing 314. Removal of the stand 316 can be advantageous to facilitate normal use of the MDI, that is, for dispensing medicament (the pharmaceutical formulation) to a patient. Where only a single pivot bar or rod 318R is provided (extending from a single upright 316U), the user can simply slide the actuator housing 314 off the pivot rod or bar 318R. Where two pivot rods or bars 318R are used, at least one of the uprights 316U user can be resiliently deformable such that the pivot bar or rod 318R can be removed from the bore or passage by deflection of the respective upright 318U. The actuator housing 314 can subsequently be replaced in the stand 316 in similar manner. Removal and replacement of the actuator housing 314 from the stand 316 can be effected multiple times without damage to, or modification of, the actuator housing 314 or the stand 316.

[0071] Apparatus 310 can further include a measurement component 320 which is conveniently in the form of a scale or indicator. In some preferred arrangements, scale or indicator 320 can be pivotally mounted to the stand 316. Specifically, the scale or indicator can be pivotally suspended from the stand 316. In some preferred arrangements, the scale or indicator 320 can be pivotally suspended from the pivot bar or rod 318R about which the actuator housing 314 also pivots. In other preferred arrangements the pivot from which the scale or indicator 320 is pivotally suspended can be spatially separate from the pivot bar or rod 318R. It is of course advantageous that the scale or indicator 320 is mounted in a location which is close to the actuator housing 314 so that a determination of an angle of inclination of the actuator housing 314 (such angle equating to an indication of the amount of formulation contained in the canister 312) can be made by taking a reading from the scale or indicator 320.

[0072] The manner in which a user can make a measurement of the (remaining) contents of the canister 312 is in its general principles the same as that of the

embodiments described in relation to Figures 1A to 1 C and Figures 2A and 2B. Thus, use of the apparatus 310 of this embodiment can also be simple for many patients, including those who may suffer a physical impairment. Firstly, the user mounts the canister receiving element 314 to the support element 316 to (if not already so mounted). More specifically, the user mounts the actuator housing 314 the pivot bar(s) or rod(s) 318R of the stand 316. Generally, the canister 312 will already be in the actuator housing 314, but if not, the user places the canister 312 in the actuator housing 314. The canister receiving element 314 is thus suspended from the pivot rod(s) or bar(s) 318R so that the canister receiving element 314 (actuator housing 314) is not in contact with any other surface or structure and is therefore free to move about its pivot. In preferred configurations the construction of the stand 316 is such that when the canister receiving element 314 is mounted to the pivot rod(s) or bar(s) 318R the pivot axis is substantially horizontal. Some variation from the horizontal can be acceptable if, for example, the surface on which the stand 316 rests itself varies to some small extent from the horizontal. The canister receiving element 314 with the canister 312 received therein can thus settle to its rest position, at which time the user can take a reading from the scale or indicator 320 in a manner corresponding to that described above in relation to Figures 1A to 1C and Figure 2A and 2B. It is noted in this respect that the pivotal suspension of the scale or indicator 320, in accordance with some embodiments of the invention, can be advantageous in ensuring consistency between successive measurements. Thus by pivotally suspending both the scale or indicator 320 and the canister receiving element 314 with the canister 312 therein, both achieve a consistent rest position irrespective of variations in an angle of inclination of the stand 316 such a might be caused if the stand 316 rests on surfaces which are not completely horizontal.

[0073] A further alternative embodiment of an apparatus according to the invention is illustrated with reference to Figures 4A to 4D and Figures 5A to 5E.

[0074] In the embodiment as illustrated in Figures 4A to 4D, the apparatus 410 for determining a quantity of a pharmaceutical formulation in a metered dose inhaler canister can comprise a support assembly 411 including a support element 416 and a canister receiving element 414 supported by the support element 416. The support assembly 411 can define a pivot structure about which the canister receiving element 414 with the canister 412 received therein is free to pivot with respect to the support element 416. The apparatus 410 can be configured such that the centre of gravity of the canister receiving element 414 with the canister 412 received therein is not coincident with the pivot. The apparatus 410 can further comprise a measurement component 420 configured for determining a rest angle of said canister receiving element 414 with the canister 412 received therein when supported by the support element 416.

[0075] Canister 412 can be a conventional canister as used in a conventional metered dose inhaler, such as the canister 912 discussed above in relation to Figure 6. For the purposes of measurement of the quantity of pharmaceutical formulation contained in the canister 412 with the apparatus 410, the canister is removed from the metered dose inhaler. Typically, as noted in relation to the embodiments described above, in a metered dose inhaler, the canister is contained in an actuator housing. Such actuator housing is not part of the presently described embodiment.

[0076] The canister receiving element 414 of the apparatus 410 can comprise a base wall portion 430, at least one canister retaining formation 432 extending at a first side of said base wall portion 430 and a stabilising portion 434 arranged at an opposed second side 430S of said base wall portion 430. The base wall portion 430 can comprise at said second side 430S a concave (e.g. dished or part-spherical) surface 430C. Said concave surface 430C can extend over substantially the whole of the second side 430S of the base wall portion 430 or can comprise only a part thereof.

[0077] The support element 416 can comprise an upstanding bar or rod 416 having an upper end 416RU. In some preferred embodiments the bar or rod 416R can be arranged substantially vertically in use of the apparatus 410. Bar or rod 416 can conveniently be made from a suitable metal, but other materials such as polymeric materials can also be suitable. Upper end 416RU of bar or rod 416 can be tapered towards a point, the point forming the uppermost limit of the bar or rod 416R. For example, the uppermost end of the bar or rod 416 can be generally conical. In other embodiments, upper end 416RU of bar or rod 416 can have a curved convex shape, such as a domed or part spherical shape.

[0078] In some preferred embodiments, the upstanding bar or rod 416R can be mounted to, or integral with, and can extend from, a base 416B. Base 416B can be relatively heavy and configured to allow the apparatus 410 to stand stably in use on a nominally horizontal surface such as a table, shelf, worktop or the like. In some preferred embodiments the base 416B can conveniently be made from a substantially solid block of a relatively heavy material, such as stone, ceramic materials, a metal or alloy having a density of the same order of magnitude as iron, steel or the like. However, the construction of the base 416B is not particularly limited provided that a stable support in use for the remainder of the apparatus 410 can be achieved.

[0079] In use of the apparatus 410, the canister receiving element 414 can be mounted on said bar or rod 416R with said concave surface 430C in contacting relation with said bar or rod upper end 416RU. The concave surface 430C can serve to ensure a correct location of the upper end 416RU at the second side of the base wall portion 430, which in some embodiments can be at the centre of said second side or in other embodiments can be offset from the centre. The canister receiving element 414 can thus rest on, and be supported only by, said upper end 416RU of the bar or rod 416R. The concave surface 430C and the bar or rod upper end 416RU can thus define a pivot structure about which the canister receiving element 414 with the canister 412 received therein is free to pivot with respect to the support element 416.

[0080] Canister 412 is in use of the apparatus 410 mounted to canister receiving element 414. As noted the canister receiving element 414 includes at least one canister retaining formation 432 configured to retain the canister in or on the canister receiving element. The canister is in some preferred embodiments mounted to the canister receiving element at an opposed side of said base wall portion 430 from the stabilising portion 434. The canister retaining formation can in principle take any form suitable for mounting the canister 412 to the canister receiving element and maintaining the canister during use of the apparatus in such mounted configuration. In one convenient arrangement the canister retaining formation can comprise a substantially annular wall upstanding from said base wall portion 430. The upstanding substantially annular wall can define an internal well into which the canister can be received such that the base of the canister is juxtaposed with a face of the base wall portion 430 which is opposed to said concave face 430C. The upstanding substantially annular wall portion can have an inner annular wall surface of a diameter which, in relation to the diameter of the canister 412, can be such as to retain the canister 412 in the well, in part, by friction between the said wall surface and the outer surface of the canister. Given the location of the canister 412, in use of the apparatus 410 for measurement, above the base wall portion 430, gravity is (also) effective in retaining the canister 412 in its mounted position.

[0081] In preferred constructions the stabilising portion 434 can be configured such that the centre of gravity of the canister receiving element 414 (with the canister 412 received therein) is below said upper end 416RU of the bar or rod 416R. Stated differently, in such embodiments, the centre of gravity of the canister receiving element 414 (with the canister 412 received therein) is below the pivot structure. In convenient arrangements such positioning of the centre of gravity can be achieved by configuring said stabilising portion 434 to extend downwardly (with respect to the configuration of the apparatus 410 in use) away from said base wall portion 430 and concave surface 430C. The stabilising portion 434 can be relatively massive, thereby to ensure that the centre of gravity of the canister receiving element 414 with the canister 412 received therein is below the pivot point, even when the canister 412 is full. Conveniently the stabilising portion can be made from a relatively heavy (dense) material, such as a metal, for example steel. Typically such a downwardly extending part of said stabilising portion can be a downwardly extending side wall portion, extending from a circumference of said base wall portion 430. The side wall portion can extend continuously about said circumference and can extend downwardly to a lower limit or edge without any gap or break.

[0082] Thus in one convenient form said stabilising portion can comprise a continuous, unbroken, skirt portion 434SP extending downwardly from said base wall. The skirt portion 434SP can conveniently be in the form of a substantially cylindrical wall. In other arrangements the skirt portion 434SP can include breaks or gaps. The skirt portion 434SP can thus define a lower side (with respect to base wall portion 430) well 434W bounded by second side of base wall portion 430 (including concave portion 430C) and by an inner face 434J of said skirt portion cylindrical wall. Thus for mounting the canister receiving element 414 to the bar or rod 416R, an upper part of the bar or rod 416R is received into said well 434W until the upper end 416RU of the bar or rod 416R contacts the concave surface portion 430C.

[0083] The apparatus 410 can comprise a biasing element of said support assembly 411 configured such that the centre of gravity of the canister receiving element 414 with the canister 412 received therein is not coincident with the pivot. As noted, the canister receiving element 414 is free to pivot on said bar or rod 416R and the present invention exploits said pivoting action to provide an indication of the quantity of pharmaceutical formulation which is contained from time to time in canister 412. In particular, the rest angle which the canister receiving element 414 adopts when mounted on the bar or rod 416 is indicative of the amount of pharmaceutical formulation contained in the canister 412.

[0084] However if the canister receiving element 414 is entirely rotationally uniform (i.e. is identical along any radius extending in a given plane perpendicular to the longitudinal axis), and if therefore the concave portion 430C is arranged centrally with respect to the base wall portion 430, then a variation in quantity of pharmaceutical formulation contained in the canister 412 will not result in a variation in the rest angle of the canister receiving element 414 (to which the canister 412 is mounted). In this particular case, a variation in the amount of pharmaceutical formulation in the canister will result in a displacement of the centre of gravity of the canister receiving element 414 with the canister 412 retained therein, but such displacement will be along a vertical axis through the pivot and will not therefore result in an angular displacement of the canister receiving element 414.

[0085] It follows that the support assembly 411 should be constructed such that a variation in the amount of pharmaceutical formulation in the canister will result in a displacement of the centre of gravity of the canister receiving element 414 with the canister 412 retained therein which displacement includes a radial component either towards or away from said vertical axis through the pivot. It is noted that in a rest condition of the canister receiving element 414 with the canister 412 retained therein when supported on the pivot, the centre of gravity lies on the vertical axis through the pivot. A change in the amount of pharmaceutical formulation contained in the canister 412 which causes a radial displacement of the centre of gravity effectively creates a turning moment so that the canister receiving element 414 with the canister 412 retained therein is displaced about the pivot until the centre of gravity again lies on the said vertical axis.

[0086] Hence some non-uniformity, bias or eccentricity is provided in or on the canister receiving element 414, or in its mounting to the pivot (upper end 416RU). In practical terms, such non-uniformity or eccentricity can have the consequence that, in embodiments of the invention, the rest position of the canister receiving element 414, when the canister is not mounted thereto, is inclined with respect to the vertical, or, stated differently, the longitudinal axis of the canister receiving element 414 is non-vertical (and preferably is slightly offset from the vertical) when the canister receiving element 414 is mounted to the bar or rod 416. Typically an offset from the vertical of less than 5°, such as about 2° can be suitable. [0087] In some embodiments, for providing such non-uniformity or eccentricity a biasing element can be provided on, or as a part or characteristic of, the canister receiving element 414. In some embodiments the said biasing element can be an inherent characteristic of the canister receiving element 414 such as a locally thickened or thinned or absent wall region of the skirt portion 434SP. In other arrangements, the biasing element can be a discrete component, such as a small weight, attached to the canister receiving element 414, such as to the skirt portion 434SP.

[0088] In further embodiments the biasing element can be achieved by positioning the concave portion 430C of the base wall portion 430 eccentrically (i.e. other than centrally) with respect to the base wall portion 430. The pivot between the canister receiving element 414 and the bar or rod 416 is thus offset from the longitudinal axis of the canister receiving element 414.

[0089] In further embodiments the biasing element can be achieved by configuring the canister retaining formation 432 such that the longitudinal axis of the canister 412 when received in the canister retaining formation 432 is offset from the longitudinal axis of the canister receiving element 414. In this embodiment the concave portion 430C of the base wall portion 430 can be (but is not essentially) positioned centrally with respect to the base wall portion 430. In this latter configuration, the pivot between the canister receiving element 414 and the bar or rod 416 can thus be coincident with the longitudinal axis of the canister receiving element 414.

[0090] Referring now also to Figures 5A to 5D, differences in the rest angle of the canister receiving element 414 (with the canister 412 mounted thereto) when mounted to the bar or rod 416R can be seen. In Figures 5A to 5D respectively different quantities of pharmaceutical formulation are contained in the canister 412. Figure 5A shows the angular position of the canister receiving element 414 when an empty or substantially empty, canister 412 is mounted thereto. Figures 5B to 5D show the angular position of the canister receiving element when canisters containing progressively higher amounts of pharmaceutical formulation are mounted thereto. In the specific embodiment illustrated, and by way of example only, the canister 412 in Figure 5B contains 5ml of pharmaceutical formulation, the canister 412 in Figure 5C contains 10ml of pharmaceutical formulation and the canister 412 in Figure 5D contains 15ml of pharmaceutical formulation. It can be seen from Figures 5A to 5D that a higher amount of pharmaceutical formulation contained within the canister 412 results in a greater angle of inclination of the canister receiving element 414 (with the canister 412 mounted thereto) with respect to the vertical. Thus, a user can judge the approximate amount of the contents of the canister 412 by the rest angle which the canister receiving element 414 (with the canister 412 mounted thereto) adopts. The user can be warned that the contents (i.e. the pharmaceutical formulation) of the canister 412 will run out after a relatively small number of further doses as the rest angle of the canister receiving element approaches the vertical.

[0091] To assist the user in determining the quantity of the contents (pharmaceutical formulation) within the canister 412, a measurement component 420 such as a scale or indicator can be provided. In the example for Figures 5A to 5D, the scale or indicator is a graduated scale (which only for ease of illustration is a metal ruler). The scale or indicator 420 can usefully be mounted to the base 416B. A pointer or the like (shown schematically as a solid white arrow 421 W) can be provided on the canister receiving element 414 to facilitate reading of the scale 420.

[0092] In one alternative configuration, the scale or indicator 420 can be a graphical, alphabetical or alphanumeric scale. Such a scale can be mounted in an upright configuration similar to the position of numerical or graduated scale 421W. In one variation, a scale (being a numerical scale, an alphabetical scale, an alphanumeric scale or a graphical or graduated scale) can be mounted to an upper surface of the base portion 416B and may conveniently arranged substantially parallel thereto. One example of such a scale 420, which for the purposes of illustration is a graphical scale, is shown in Figure 5E. In Figure 5E the scale 421 T includes a plurality of (in this case, three) visually differentiated areas or zones 421 T-1 , 421 T-2 and 421 T-3. For example, area 420T-1 can be coloured green, area 420T-2 can be coloured orange and area 420T-3 can be coloured red. The scale 421 can be positioned such that a user can take a reading in accordance with the angle of the canister receiving element 414 and such that if said reading corresponds to the green area (421T-1 ), the user is reassured that a high quantity of pharmaceutical formulation remains in the canister 412, and, if said reading corresponds to the orange area (421 T-2) the user is advised that a significant amount of the

pharmaceutical formulation has been used up, and, if said reading corresponds to the red area (421 T-3) the user is warned that the amount of pharmaceutical formulation is low and that the metered dose inhaler will very soon be in need of replacement. A pointer or the like (shown schematically as a dashed white arrow 421 X) can be provided on the canister receiving element 414 to facilitate reading of the scale 421 T.

[0093] It is further noted that it is not a primary objective of embodiments of the present invention of the type illustrated in Figures 4 and 5 of the present invention to provide a user with a fully quantitative measure of the number of doses remaining in the canister 412. That is, the user does not need to determine an exact quantity of the pharmaceutical formulation in the canister. Rather, embodiments of the present invention seek to provide the user with a more general indication as to the remaining quantity of the pharmaceutical formulation in the canister and to give the user adequate advanced warning if such quantity is low. The user can then take appropriate steps to replace the MDI, or to carry a spare MDI which is available to use when (according to the manufacturer's

recommendations) the first MDI is exhausted.

[0094] Throughout the description and claims of this specification, the words "comprise" and "contain" and variations of them mean "including but not limited to", and they are not intended to (and do not) exclude other moieties, additives, components, integers or steps. Throughout the description and claims of this specification, the singular encompasses the plural unless the context otherwise requires. In particular, where the indefinite article is used, the specification is to be understood as contemplating plurality as well as singularity, unless the context requires otherwise.

[0095] Features, integers, characteristics, compounds, chemical moieties or groups described in conjunction with a particular aspect, embodiment or example of the invention are to be understood to be applicable to any other aspect, embodiment or example described herein unless incompatible therewith. All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and/or steps are mutually exclusive. The invention is not restricted to the details of any foregoing embodiments. The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.

[0096] The reader's attention is directed to all papers and documents which are filed concurrently with or previous to this specification in connection with this application and which are open to public inspection with this specification, and the contents of all such papers and documents are incorporated herein by reference.