Abstract:
The present disclosure relates to a dose indicator for a pressure-actuated metered dose inhaler (pMDI) device. In an embodiment, the dose indicator comprises a chassis element having a viewing portion, a display element located within the chassis element, a resilient deformable element, and an indexing element having an axis, translation of the indexing element along its axis from a first position to a second position causing deformation of the resilient deformable element in the same direction as translation of the indexing element resulting in generally greater displacement of portions of the resilient deformable element nearer to the axis relative to portions thereof further from the axis, the displacement of the portions of the resilient deformable element in the same direction as translation of the indexing element inducing indexing of the display element from a current position to a subsequent position relative to the viewing portion of the chassis element.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application claims the benefit of United Kingdom Patent Application No. 1215917.4, filed Sep. 6, 2012, which is incorporated herein by reference in its entirety. 
       TECHNICAL FIELD OF THE INVENTION 
       [0002]    The present invention relates to improvements in or relating to dose indicators, and is more particularly, although not exclusively, concerned with dose indicators for pressure-actuated metered dose inhaler (pMDI) devices. 
       BACKGROUND TO THE INVENTION 
       [0003]    Patients that need to use inhalers, such as pMDI devices, regularly have long had the need to be able to monitor their inhaler usage, and regulators of medicines have started to specify that some indication of when an inhaler is reaching the end of its recommended number of actuations as well as when it has reached or exceeded that number is integrated into the inhaler product. Dose counters (providing an accurate count of the number of doses remaining) and dose indicators (providing an indication of the number of doses remaining) have been proposed for use with inhalers. Yet, to date not many of the proposed dose counters or indicators for pMDIs have reached the market in a pMDI product. In most dose counters and dose indicators, the display is typically advanced each time the inhaler device is used, and it is particularly important that they do not undercount the number of dispensed doses as, in extreme cases, the patient may rely on the count shown on the pMDI device to receive life-saving medication. In dose counters or dose indicators, it may be acceptable for advancement of the display to be triggered (initiated) before or after the dose has been delivered, so long as it is practically impossible for the patient to trigger it without dispensing a dose. However, some of these dose counters or dose indicators are designed to require electronics which increases the cost, prevents the user from washing the device, may have battery life issues and, in the case of dose counters, may have difficulty obtaining regulatory approval for their use. In addition, many of these dose counters and/or dose indicators are complex requiring large numbers of small mechanical parts which gives rise to high costs, difficulties in assembly, and the requirement for complex dimensional tolerances. The added cost has long been a disincentive to product developers to incorporate a dose counter into an inhaler. In some instances, the dose counters and dose indicators require a re-design of what has become a standard shape and size of pMDI to significantly larger, bulkier and more awkward shapes. In addition, the character size and legibility of the display of such devices can be poor, making it difficult for a user to read them. 
         [0004]    Examples of pMDI inhalers or devices having either dose counters or dose indicators are described in GB-A-1317315, WO-A-93/24167, U.S. Pat. No. 7,806,295, U.S. Pat. No. 5,421,482, U.S. Pat. No. 6,679,251, WO-A-02/91293, GB-A-2385640, WO-A-2006/119766, WO-A-2006/126965 and WO-A2008/025087. 
         [0005]    GB-A-1317315 discloses a dose indicator that can be mounted in a pMDI actuator and which comprises four sets of advancement teeth which are sprung-loaded together. GB-A-2385640 discloses a dose indicator which is mountable within a pMDI actuator and which uses sets of fine teeth to advance the indicator. 
         [0006]    WO-A-93/24167 discloses a two-component dose indicator that is mounted at the top of a pMDI actuator. WO-A-2006/126965 discloses a top-mounted dose indicator. WO-A-2008/025087 also discloses a top-mounted pMDI dose indicator in which an indicator ring component bears integral spring arms. 
         [0007]    U.S. Pat. No. 7,806,295 discloses a dose indicator driven by a flexible tab attached to a ring. U.S. Pat. No. 5,421,482 discloses a mechanical dose indicator driven round by a ring of flexible arms on a rigid plate. WO-A-2006/119766 discloses a pMDI dose indicator comprising a single component for use with an unconventional rotary metering valve; thereby requiring modifications to the pMDI inhaler unit or to the actuator in which it is mounted. 
         [0008]    U.S. Pat. No. 6,679,251 discloses a bottom-mounted pMDI dose counter which incorporates two C-springs the serve both to reset the dose counter and to provide follow-through for the valve firing of the inhaler. WO-A-02/91293 discloses a counter mechanism operated by a collapsible flexible ‘spider’. 
       SUMMARY OF THE INVENTION 
       [0009]    Each of the dose indicators or dose counters described above tends to involve features that would build expense into the finished design, and cannot be considered suitable for use in price-sensitive markets. 
         [0010]    One drawback with existing dose indicators is the number of components required for their construction. In some cases, there may be in excess of six components in the dose indicator. This tends to make such dose indicators expensive to manufacture both in terms of component cost and overall material cost. In addition, due to the number of components, there are substantial assembly costs. 
         [0011]    Another drawback is the stack-up of dimensional tolerances of the components of the dose indicator. If many components are required to manufacture the dose indicator, the tolerance of each component needs to more predictable to ensure that the dose indicator operates as intended. This involves significant development time to optimise the dimensions and means that the number of components has an effect on the accuracy and reliability of the dose indicator during operation. There are also issues with combining components that have dimensions at the edge of tolerance, to ensure that the total stack of tolerances does not impede performance and that acceptable combinations are not unduly rejected. There are also issues with combining components that are at the edge of tolerance, to ensure that the total stack of tolerances does not impede performance and that acceptable combinations are not unduly rejected. There are also issues with combining components that are at the edge of tolerance, to ensure that the total stack of tolerances does not impede performance and that acceptable combinations are not unduly rejected. 
         [0012]    The issue of cost is a particular concern when considering dose indicators for highly price-sensitive markets, for example, Asia. 
         [0013]    The present invention seeks to provide a dose indicator that can be manufactured at low cost so that it becomes an attractive proposition even in price-sensitive markets. Here and in the following description, the term “dose indicator” is intended to refer to both dose counter devices and dose indicator devices. 
         [0014]    It has been recognised that in order to provide a dose indicator that can be manufactured at low costs, it would be desirable to provide a dose indicator that has fewer components. 
         [0015]    Further it is desirable to provide an inexpensive, simple and reliable dose indicator that would be compact in size so that it could, at the same time, be inserted or fitted into a housing of a typical commercial inhaler, in particular into an actuator of a pressure-actuated metered dispensing device of similar shape and comparable size to existing, commercial actuators. 
         [0016]    In accordance with a first aspect of the present invention, there is provided a dose indicator for a pressure-actuated metered fluid dispensing device, the dose indicator comprising: 
         [0017]    a chassis element having a viewing portion; 
         [0018]    a display element located within the chassis element; 
         [0019]    a resilient deformable element; and 
         [0020]    an indexing element having an axis, translation of the indexing element along its axis from a first position to a second position causing deformation of the resilient deformable element in the same direction as translation of the indexing element resulting in generally greater displacement of portions of the resilient deformable element nearer to the axis relative to portions thereof further from the axis, the displacement of the portions of the resilient deformable element in the same direction as translation of the indexing element inducing indexing of the display element from a current position to a subsequent position relative to the viewing portion of the chassis element. 
         [0021]    It is to be recognised that the phrase “resulting in generally greater displacement of portions of the resilient deformable element nearer to the axis relative to portions thereof further from the axis” is to be understood that, in each instance, a generally greater displacement occurs nearer to the axis than further away from the axis. Preferably, the outline shape of the resulting displacement of the resilient deformable element is symmetrical about the axis. More preferably, the resulting outline shape may be an inverted frustum of a cone. 
         [0022]    In one embodiment of the invention, the elements of the dose indicator are advantageously formed in a maximum of three components. In another embodiment, the dose indicator advantageously comprises only two components. By substantially reducing the number of components, the overall cost of a dose indicator in accordance with the present invention is substantially reduced. In addition, a dose indicator in accordance with the present invention can simply be slotted over a nozzle block in an actuator for a pressure-actuated metered dispensing device. 
         [0023]    Preferably, the resilient deformable element is arranged around the axis of the indexing element. Ideally, the display element is also arranged around the axis of the indexing element. By having the resilient deformable element and the display element arranged around the axis of the indexing element, the components can easily be aligned with respect to the actuator in which the dose indicator is to be located and with respect to the associated pressure-actuated metered dispensing device. Preferably, the dose indicator is designed such that, when it is assembled into a pressure-actuated metered fluid dispensing device, the axis of the indexing element coincides with the central vertical axis of a stem socket or nozzle block of the pressure-actuated metered fluid dispensing device. 
         [0024]    The display element may comprise a continuous display ring or a discontinuous display ring. By having the display element in the form of a display ring, the dose indicator can easily be indexed with respect to the housing in which it is located. 
         [0025]    In one embodiment, the display element may comprise a disc centred about the axis of the indexing element. Again, this provides inherent alignment of the display element with respect to the indexing element. 
         [0026]    Preferably, the indexing element comprises a tube element connected to the resilient deformable element. 
         [0027]    Advantageously, the resilient deformable element comprises a grille element. A further grille element may be located adjacent the resilient deformable grille element so that it substantially abuts the resilient deformable grille element in the first position to restrict the passage of air through the abutting grille elements. 
         [0028]    When the indexing element is in the second position, the resilient deformable grille element is spaced from the further grille element to allow the passage of air through the spaced apart grille elements. The cooperation between the deformable grille element and the further grille element advantageously ensures that the user is able to coordinate their inspiratory breath with their actuation of the pressure-actuated metered dispensing device. Moreover, such embodiments advantageously allow for the provision of a dose indicator that includes breath coordination functionality without increasing the overall cost of the dose indicator. 
         [0029]    The further grille element may be associated with one of: the display element and the chassis element. In this case, the resilient deformable grille element is preferably associated with the other one of: the display element and the chassis element. 
         [0030]    In one embodiment of the present invention, the chassis element may comprise a housing including a base portion and a lid portion, the base portion including the indexing element and the resilient deformable grille element. The lid portion is desirably connected to the base portion by a living hinge, and is closable with respect to the base portion. 
         [0031]    This arrangement of the chassis element provides an effectively self-contained unit that can simply be inserted into an actuator of the pressure-actuated metered dispensing device, fitting into position over a stem socket or nozzle block in the housing. 
         [0032]    Preferably, the base portion comprises a wall portion having the viewing portion formed therein. This viewing portion is desirably aligned with a window provided in the actuator of the pressure-actuated metered device when the dose indicator is inserted therein. 
         [0033]    Advantageously, the housing forming the chassis is formed as one component. 
         [0034]    In one embodiment, the display element may comprise the further grille element mentioned supra and be housed within the housing. The further grille element may be substantially rigid or it may be fixed. A rack may be formed on a portion of the display element by which it is indexed with respect to the viewing portion. 
         [0035]    Advantageously, in embodiments in which the display element comprises the further grille element, the display element and further grille element are formed as one component. 
         [0036]    In order to implement the indexing of the display element with respect to the viewing portion, desirably the housing further comprises a worm element arranged to engage with the rack formed on the display element, rotation of the worm element indexing the display element with respect to the viewing portion. 
         [0037]    It is preferred that the worm element comprises a plurality of teeth located on at least a portion thereof. The worm element may comprise an axle portion at each end, the plurality of teeth being located between the two axle portions. Advantageously, a locking pawl is provided for engaging with at least one tooth formed on the worm element. 
         [0038]    Ideally, the worm element is supported by first and second support members formed on the chassis element, the first and second support members advantageously being integrally formed with the lid portion. Advantageously, the first and second support members each have a through-hole to receive an end of the worm element, the through-holes being moulded using an injection moulding tool that opens along an axis substantially perpendicular to an axis defined by the centres of the through-holes. 
         [0039]    Advantageously in those embodiments including a base portion, an advancement arm is provided in the base portion which is operable to rotate the worm element as the indexing element moves between the first and second positions. Preferably, the advancement arm and the base portion are integrally formed. 
         [0040]    The spacing of the rack preferably corresponds to the flight of the worm element. 
         [0041]    In a further embodiment, the lid portion may include at least one additional spring arm that engages with a hole provided in the side of the indexing element. This provides a restorative upward force to the resilient deformable element even in its rest position. 
         [0042]    In alternative embodiments to those where the chassis element comprises a housing including a base portion and a lid portion, the base portion including the indexing element and the resilient deformable grille element, the chassis element may favourably comprise an inner wall portion and an outer wall portion joined by a rim portion, the inner and outer wall portions defining an annulus therebetween, the display element being mounted within the annulus with a portion of the display element being visible through the viewing portion formed in the outer wall portion. 
         [0043]    Preferably, the chassis element includes a first set of chassis element teeth located within the annulus adjacent the rim portion and a second set of chassis element teeth associated with the outer wall portion and spaced from the rim portion. In addition, the outer wall portion may comprise a plurality of clip elements extending therefrom on which the second set of chassis element teeth is formed. Moreover, the first and second sets of chassis element teeth face one another and are integrally formed with the chassis element. Advantageously, the first and second sets of chassis element teeth are offset with respect to one another. In a similar way to the other embodiments, the chassis element is advantageously formed as one component. 
         [0044]    In such embodiments, the display element may comprise first and second sets of display element teeth located on respective peripheral edges thereof, the first and second sets of chassis element teeth engaging with respective ones of the first and second sets of display element teeth in accordance with the first and second positions of the indexing element. In such embodiments, the display element may comprise the resilient deformable grille element and the indexing element, the resilient deformable grille element connecting the display element to the indexing element. 
         [0045]    The display element is preferably formed as one component. 
         [0046]    In addition, in such embodiments, translation of the indexing element to the second position favourably causes engagement of the second set of chassis element teeth with the second set of display element teeth to rotate the display element through a fraction of an indexing pitch in a first direction, and translation of the indexing element back to the first position causes engagement of the first set of chassis element teeth with the first set of display element teeth to rotate the display element through a remaining fraction of the indexing pitch in the first direction. 
         [0047]    In such embodiments, the chassis element may further comprise a chassis element spring arranged to maintain engagement of the first set of chassis element teeth with the first set of display element teeth when the indexing element is in the first position. In addition, the chassis element spring may comprise the further grille element, the chassis element spring being connected to the inner wall portion. 
         [0048]    In accordance with another aspect of the present invention, there is provided a pressure-actuated metered dispensing device comprising: an actuator portion; a window formed in the actuator portion; a dispensing portion; a nozzle block located between the actuator portion and the dispensing portion; a dose indicator as described above, the indexing element being aligned with the nozzle block and the viewing portion being aligned with the window in the actuator portion; and a canister comprising a container and a metering valve housed within the actuator portion, the metering valve having a valve stem that engages the nozzle block and wherein, in use, relative movement of the container and the nozzle block causes the translation of the indexing element from the first to the second position as a result of engagement of a portion of the canister and the indexing element. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0049]    For a better understanding of the present invention, reference will now be made, by way of example only, to the accompanying drawings in which: 
           [0050]      FIG. 1  illustrates an isometric top view of an exemplary actuator for a pMDI inhaler without a dose indicator; 
           [0051]      FIG. 2  is similar to  FIG. 1  but illustrates an isometric sectioned top view of an exemplary actuator for a pMDI inhaler; 
           [0052]      FIG. 3  is similar to  FIG. 1  but illustrates an exemplary dose indicator of the present invention located within the actuator; 
           [0053]      FIG. 4  illustrates an isometric top view of a dose indicator in accordance with a first exemplary embodiment of the present invention; 
           [0054]      FIG. 5  illustrates an isometric top view of the dose indicator shown in  FIG. 4  but with its lip open; 
           [0055]      FIG. 6  illustrates a sectioned side view of the dose indicator shown in  FIG. 5 ; 
           [0056]      FIG. 7  illustrates a chassis element in accordance with the first exemplary embodiment of the present invention; 
           [0057]      FIG. 8  illustrates an isometric top view of a worm element in accordance with the first exemplary embodiment of the present invention; 
           [0058]      FIG. 9  illustrates an isometric top view of a display element in accordance with the first exemplary embodiment of the present invention (display numerals not being shown); 
           [0059]      FIG. 10  illustrates a sectioned side view of the dose indicator in accordance with the first exemplary embodiment of the present invention with its lid partially open; 
           [0060]      FIG. 11  illustrates a sectioned side view of the dose indicator in accordance with the first exemplary embodiment of the present invention with its lid closed; 
           [0061]      FIG. 12  illustrates another sectioned side view similar to that of  FIG. 11 , but illustrates the engagement of the worm element with an indexing arm; 
           [0062]      FIG. 13  illustrates a sectioned side view of the dose indicator in accordance with the first exemplary embodiment of the present invention mounted within a actuator of a pMDI inhaler; 
           [0063]      FIG. 14  illustrates a sectioned isometric view of a pMDI inhaler having a dose indicator in accordance with the first exemplary embodiment of the present invention; 
           [0064]      FIG. 15  illustrates a sectioned side view of a chassis element in accordance with the first exemplary embodiment of the present invention in its second or displaced position; 
           [0065]      FIG. 16  illustrates a cross-section of a dose indicator in accordance with the first exemplary embodiment of the present invention with the indexing element in its first or rest position; 
           [0066]      FIG. 17  is similar to  FIG. 16  but illustrates the indexing element in its second or displaced position; 
           [0067]      FIG. 18  illustrates a partial isometric top view of a chassis element in accordance with a second exemplary embodiment of the present invention, the lid not being shown for clarity; 
           [0068]      FIG. 19  is similar to  FIG. 18  but also illustrates the display ring within the chassis element; 
           [0069]      FIG. 20  is similar to  FIG. 19  but also illustrates the worm element; 
           [0070]      FIG. 21  illustrates an isometric top view of the lid part only of the chassis element in accordance with the second exemplary embodiment of the present invention; 
           [0071]      FIG. 22  illustrates an isometric top view of the assembled dose indicator in accordance with the second exemplary embodiment of the present invention; 
           [0072]      FIG. 23  illustrates an isometric top view of a dose indicator in accordance with a third exemplary embodiment of the present invention; 
           [0073]      FIG. 24  illustrates an isometric bottom view of a dose indicator in accordance with the third exemplary embodiment of the present invention; 
           [0074]      FIG. 25  illustrates an isometric top view of a chassis element in accordance with the third exemplary embodiment of the present invention; 
           [0075]      FIG. 26  illustrates an isometric bottom view of a chassis element in accordance with the third exemplary embodiment of the present invention; 
           [0076]      FIG. 27  illustrates an isometric top view of a display element in accordance with the third exemplary embodiment of the present invention (not all display numerals being shown); 
           [0077]      FIG. 28  illustrates an isometric bottom view of the display element of  FIG. 27  (display numerals not being shown); 
           [0078]      FIG. 29  illustrates a sectioned isometric top view of the dose indicator in accordance with the third exemplary embodiment of the present invention in its first or rest position; 
           [0079]      FIG. 30  is similar to  FIG. 29  but illustrates the display ring and viewing window; 
           [0080]      FIG. 31  is similar to  FIG. 29  but illustrates the dose indicator in its second or displaced position; and 
           [0081]      FIG. 32  illustrates a sectioned isometric top view of the assembled dose indicator in accordance with the third exemplary embodiment of the present invention mounted within a pMDI actuator. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0082]    The present invention will be described with respect to particular exemplary embodiments and with reference to certain drawings but the invention is not limited thereto. The drawings described are only schematic and are non-limiting. In the drawings, for illustrative purposes the size of some of the elements may be exaggerated and not drawn to scale. 
         [0083]    It will be understood that the terms “vertical”, “horizontal”, “top”, “bottom”, “above”, “below”, “left”, “right” etc. as used herein refer to particular orientations of the Figures and these terms are not limitations to the specific embodiments described herein. 
         [0084]    As mentioned above, in addition to reducing the cost of a dose indicator for use with pMDI inhalers, it is desirable to provide a dose indicator that includes breath coordination functionality without increasing the overall cost of the dose indicator. The exemplary dose indicators shown in  FIGS. 4 to 31  include such breath coordination functionality. However as described below, if desired or needed, these dose indicators can be simply modified in such a manner that this functionality is removed, while still maintaining an advantageous inexpensive, simple and reliable dose indicator. 
         [0085]    Before turning to the exemplary embodiments, breath actuation and coordination are described in the following paragraphs to ensure a proper understanding of the breath coordination functionality of the exemplary embodiments. 
         [0086]    Many users of pMDI inhalers find it difficult to time correctly the moment at which they actuate their pMDI inhaler relative to the moment at which they start to inhale. Further, a significant number of other users do not realise that they have a problem with coordinating their in-breath with the actuation of the pMDI inhaler and therefore do not realise that they are not receiving an optimum dose each time. Naturally, not being able to have the correct coordination leads to not having optimum treatment as possibly a large percentage of each dose is not inhaled. Accordingly, there is a general ongoing need for many pMDI users to have an inhaler that maximises the dose of the particular drug being delivered to their lungs via their inhaled inspiratory breath. 
         [0087]    There are currently two main solutions to this problem, namely, breath actuation where a triggering mechanism utilises the inhalation of a user to release the pMDI valve; and breath coordination where the inhalation and the release of the dose are timed to coincide in some other way. The former solution (“breath actuation systems”) tends to involve complex (and therefore expensive) mechanisms, whilst the latter solution (“breath coordination systems”) can be much simpler and therefore cheaper. 
         [0088]    Many breath coordination systems fit into one of two categories: “can&#39;t inhale until press” and “can&#39;t press until inhale”. The former category typically involves air passageways through the inhaler that only open when the user pushes down on the pMDI canister (the assembly comprising the container and metering valve). In the latter category, it is not possible to press the pMDI inhaler downwards until some mechanical obstruction has been removed as a consequence of inspiration (e.g. had been unblocked by movement of a breath-operated obstructive vane). Thus inhalation by the patient effectively allows movement of the container to operate a dispensing valve associated with the container. 
         [0089]    It should be appreciated that many prior art dose indicators are not compatible with the inspiratory systems mentioned above, nor provide a mechanism in themselves for breath actuation or coordination. 
         [0090]    As will be explained in detail below, certain advantageous embodiments of dose indicators in accordance with the present invention include an integrated breath coordination system of the “can&#39;t inhale until press” type of operation. This operation will be described in more detail below. 
         [0091]    Referring initially to  FIGS. 1 and 2 , an exemplary actuator  100  for a pMDI inhaler (the inhalation canister not being shown) is shown. The actuator is similar in size and shape to many marketed pMDI actuators. The actuator  100  comprises a tubular housing portion  110  and a tubular mouthpiece portion  120 . At the closed bottom end of the tubular housing portion  110  sits a nozzle block  130  that comprises a stem socket  140  in flow communication with a sump region  150  and an exit orifice  160 . At the back of the tubular housing portion  110  is a viewing window  170 . At the bottom of the actuator  100  is a thumb grip  180 . An actuator running surface  190  is provided adjacent to the lower end of the tubular housing portion  110 . 
         [0092]      FIG. 3  is similar to  FIG. 1  but illustrates a display element  200  that is visible through the viewing window  170  of the actuator  100 . The display element  200  forms part of a dose indicator in accordance with the present invention. As will be described in more detail below, the display element may comprise a ring (not shown), in particular a continuous ring or a discontinuous ring, or alternatively a disc. 
         [0093]    In accordance with a first exemplary embodiment of the present invention, the dose indicator  300  comprises three principal components, namely, a chassis element  310 , a display element  320  and a worm element  330 . It is intended for use with a pMDI inhaler actuator  100 , for example, as described with reference to  FIGS. 1 to 3  above, and a pMDI canister as will be described in more detail below with respect to  FIG. 14 . The form and use of such a pMDI canister will be familiar to those skilled in the art. 
         [0094]    Referring now to  FIGS. 4 to 12 , the exemplary dose indicator  300  is shown in more detail. The chassis element  310  which has a generally rigid outer wall  340 , joined via a living hinge  350  to a lid  360 . At two points on the outer wall  340 , flexible clips  370  are provided that serve to engage with two corresponding tabs  380  on the periphery of the lid  360 . This engagement retains the lid in its closed position after assembly, as shown in  FIG. 4 . The underside  390  of the lid  360  also bears two support posts  400 ,  405  with lateral through-holes  410 ,  415  ( FIG. 7 ) that serve as bearings for an axle  420  of the worm element  330 . The support posts  400 ,  405  are angled outwardly towards their ends such that the through-holes  410 ,  415  may be injection moulded using tooling that needs no side-draw actions, thereby reducing moulding tool complexity and cost and minimising moulding cycle times. Between the two support posts  400 ,  415  is located a locking pawl  440  for engagement with the worm element  330 . 
         [0095]    Within the outer wall  340  is an annular resilient deformable grille element  450  that comprises a series of rings  460  linked by radial members  470 . The rings  460  and radial members  470  define slots  480 . The inside part of the annular resilient deformable grille element  450  extends upwards as a central alignment tube or a tubular indexing element  490 , with a central aperture  500  in which may be located the hollow male stem of the pMDI valve (not shown) when the pMDI canister is assembled into the actuator  100  with the assembled dose indicator  300 . 
         [0096]    A hooked cantilevered advancement arm  510  is mounted near the inner edge (shown as  660  in  FIG. 12 ) of the annular resilient deformable grille element  450  for engagement with the worm element  330  as will be described in more detail below. A viewing portion  520  in the form of a cut-out is provided in the outer wall  340  of the chassis element  310  through which the display element  320  can be seen when assembled. Further lid tabs  530  are provided which sit within respective recesses  540  formed in the outer wall  340  as is shown more clearly in  FIG. 4 . 
         [0097]      FIG. 8  illustrates the worm element  330  in more detail. As shown, the worm element  330  comprises a plurality of drive teeth  550  arranged around its periphery in a central region between the ends of the axle  420 . In this exemplary embodiment, there are eight drive teeth  550  which are intersected by a single-turn worm flight  560  formed in a central portion of the worm element  330 . 
         [0098]    With reference to  FIG. 9 , the display element  320  comprises a display ring  570  in the form of a cylindrical tubular wall, the outside of which bears numerals (for example,  200 ,  190 ,  180  . . . ; not shown) corresponding to the remaining number of doses of medicament in the container of the pMDI canister. Extending in from the bottom end of the display ring  570  is a substantially rigid grille element  580  in the form of rings  590  linked by radial members  600 , the rings  590  and radial members  600  defining slots  610 . A central aperture  620  is formed by the inner edge of the grille element  580 . A series of teeth in the form of a rack  625  is mounted on the top surface of one ring of the grille element  580 . 
         [0099]      FIGS. 5 ,  6  and  10  to  12  illustrate respective positions of the lid  360  with respect to the outer wall  340  as it is moved from an open position ( FIGS. 5 and 6 ) to a fully closed position ( FIGS. 11 and 12 ). 
         [0100]    The exemplary dose indicator  300  is assembled as follows. Referring to  FIGS. 4 to 9  in particular, the ends of the axle  420  of the worm element  330  are pushed into the through holes  410 ,  415  provided in respective ones of the two support posts  400 ,  405 . This is done by pushing the worm element  330  towards the underside  390  of the lid  360  so that the support posts  400 ,  405  flex outwardly by a sufficient amount to allow the axle  420  to click into place within the through holes  410 ,  415 , as shown in  FIG. 5 . The display element  320  is placed into the chassis element  310 , as shown in  FIG. 5 , being pushed over the hooked end of the advancement arm  510 , which transiently deflects inwardly to allow it to pass through the central aperture  620  in the grille element  580  of the display element  320 . Care is taken to ensure, for example, by an automated vision recognition system and/or by the provision of alignment features (not shown), that the display element  320  is orientated correctly so that it displays the correct count numerals (e.g. “200”) as seen through the viewing portion  520  of the chassis element  310 . The dose indicator is now in the part-assembled state shown in  FIGS. 5 and 6 . 
         [0101]    The final step of this very simple assembly procedure is to close the lid  360 , as is shown in the sequence of  FIGS. 5 and 6  (lid fully open),  FIG. 10  (lid partially closed), and  FIGS. 11 and 12  (lid fully closed). This movement of the lid  360  is made possible by the presence of the living hinge  350  that joins the lid  360  to the outer wall  340  of the chassis element  310 . As the lid  360  reaches its fully closed position within the top of the outer wall  340 , as shown also in  FIG. 4 , the lid tabs  380  formed on the lid  360  engage with the flexible clips  370  formed on the outer wall  340 , thereby locking the lid  360  into its fully assembled position. In the fully assembled position, the two additional alignment tabs  530  on the lid  360  engage with corresponding recesses  540  in the top of the outer wall  340 . The worm flight  560  of the worm element  330  is now engaged with the teeth of the rack  625  of the display element  320  as shown in  FIGS. 12 and 13 . 
         [0102]    Use and operation of the exemplary dose indicator may best be understood with reference to  FIGS. 11 to 17 . 
         [0103]    Once assembled, the dose indicator  300  is then pushed into the actuator  100  and over the nozzle block  130  ( FIG. 2 ), to reach the position shown in  FIG. 13 . As shown in  FIG. 13 , the outer wall  340  of the dose indicator  300  sits within the base of the tubular housing portion  110  of the actuator  100  with the viewing portion  520  of the outer wall  340  aligned with the window  170  of the actuator  100 . Desirably, the window  170  is large enough for the user to see up to two sets of numerals, for example, ‘120’ and ‘110’, so that both are visible when the actual count corresponds to an intermediate number, for example, ‘116’ or ‘115’. In this manner, the user can observe the shifted position of the display and can appreciate that the number of doses remaining has been decreased, for example, from one hundred and sixteen doses to a hundred and fifteen doses remaining The indexing element  490  sits around the nozzle block  130 , and is free to move axially upwards and downwards a certain distance with respect to the nozzle block  130  by virtue of the flexibility of the deformable grille element  450 . 
         [0104]    After the dose indicator  300  has been located within the actuator  100 , a conventional pMDI canister ( FIG. 14 ) is inserted into the stem socket  140  of the nozzle block  130  through the aperture  500  of the indexing element  490  as shown in  FIG. 14 . A valve stem  640  associated with a metering valve on the container  630  is engaged with the nozzle block  130 . Movement of the valve stem  640  towards the body of the container  630  opens the valve to dispense a metered amount of medicament. The combination of the pMDI container  630  and its associated metering valve together with the dose indicator  300  and actuator  100  is referred to hereinafter as the pMDI inhaler  650 . 
         [0105]    Downward pressure on the container  630 , in the direction of arrow ‘A’, causes the valve stem  640  to open the associated valve allowing a metered amount of medicament to pass through the exit orifice  160  and into the mouthpiece  120  (see also  FIG. 2 ). It is this downward pressure and opening of the valve to dispense a metered amount of medicament that needs to be indicated by the dose indicator  300  in accordance with the present invention. 
         [0106]    When the user requires a dose of medicament, he/she takes his/her pMDI inhaler  650  and places the mouthpiece  120  within his/her mouth. To release a dose of medicament, the user then presses down upon the free end  635  of the container  630  ( FIG. 14 ), whilst at the same time pressing upwards against the thumb grip  180 , thereby causing the container  630  to move downwardly with respect to the valve stem  640 . This movement discharges the aerosolised dose via the exit orifice  160  and mouthpiece  120  into the mouth and lungs of the user. The user then releases the downward force applied to the top  635  of the container  630 , allowing it to return upwards relative to the valve stem  640  under the influence of an internal compression spring (not shown) associated with the valve. 
         [0107]    The dose indicator  300  registers the released dose as follows. As the container  630  moves downwards during user actuation, the lower surface  633  of a ferrule  645  of the valve pushes down against the top of the indexing element  490 , causing it to move downwards relative to the outer wall  340 , lid  360 , display element  320  and worm element  330  of the dose indicator  300 . This movement is made possible by the transient downwards displacement of an inner part  660  of the deformable grille element  450  as the grille element  450  elastically deforms. This is best shown in  FIGS. 15 to 17 . 
         [0108]      FIG. 16  shows the situation where the dose indicator  300  is in its rest position, with the deformable grille element  450  in a non-deformed state and the indexing element  490  in an upward or first position.  FIGS. 15 and 17  show the indexing element  490  pushed downwardly, away from the lid  360 , the deformable grille element  450  having become transiently deformed as a consequence of this downward movement. 
         [0109]    Turning now to  FIG. 12 , as described above the advancement arm  510  is mounted on the inner part  660  of the deformable grille element  450 , and thus it will move downwardly with the indexing element  490  as it is pushed down. As the advancement arm  510  is pushed downwards, a hook  515  at its upper end engages with one of the drive teeth  550  on the worm element  330 , causing the worm element  330  to rotate clockwise as shown in  FIG. 12 . As there are eight teeth in this embodiment of the worm element  330 , the clockwise rotation is approximately 45°. Any excess “follow through” motion of the container  630  and indexing element  490 , for example, as a result of dimensional tolerances/variation, will not affect operation of the dose indicator  300  as the advancement arm  510  is free to continue downwards once it has rotated and disengaged the teeth  550  of the worm element  330 . The rotational movement of the worm element  330 , in turn, rotates the display element  320  as the worm flight  560  engages with and drives the teeth of the rack  625  on the display element  320 , the spacing of the teeth of the rack  625  corresponding to the flight of the worm element  330 . The amount of rotation of the display element  320  will not be great, however, due to the gearing provided by the use of such a worm and rack arrangement. Nevertheless, the numerals (not shown) displayed via the window  170  of the actuator  100  and viewing portion  520  of the chassis element  310  to the user will move slightly, and, after multiple successive doses, the displayed numerals will change, for example, from “200” to “190”, indicating a reduction of ten in the remaining number of medicament doses available to the user. 
         [0110]    The gearing also serves to ensure that the display element  320  cannot readily be inappropriately rotated without discharging a dose, either forwards or backwards, by user intervention, for example, by inserting something through the window  170  of the actuator  100  and viewing portion  520  formed in the outer wall  340 . 
         [0111]    Completing the actuation cycle, the resilient deformable grille element  450 , having deflected elastically, will act as a spring when it is released, serving to return the indexing element  490  back up to its rest or first position when the user stops pressing on the container  630  of the pMDI canister. The deformable grille element  450  will therefore return from the position illustrated in  FIG. 17  to that illustrated in  FIG. 16  once the pressure is released. 
         [0112]    The advancement arm  510  accordingly also returns to its own corresponding rest position. The worm element  330  cannot, however, rotate back to its previous position, as the locking pawl  440  ( FIG. 11 ) engages with its teeth  550  and prevents any rotation. The hook  515  at the end of the advancement arm  510 , meanwhile, returns past the worm teeth  550  by deflecting past them back to its first or rest position as shown in  FIG. 12 . 
         [0113]    At the end of life, that is, for a displayed count of ‘0’, an end-of-life stop feature (not shown) provides a restraint on further dose indicator display rotation. This feature could take several forms, such as missing teeth, filled in teeth, a raised boss or other feature, etc. in the display ring. 
         [0114]    As will be seen from  FIG. 16 , in its rest position, the rings  460  of the deformable grille element  450  abut and occlude the slots  610  between the rings  590  of the grille element  580  of the display element  320 , thereby providing a significant resistance to the inhalation of air through the slots of the grille elements  450 ,  580  by a user. By ensuring that the outer contours of the chassis element  310  match the inner contours of the actuator  100 , bypass air leaks round the outside of the dose indicator can be minimised. When the container  630  is pushed downwardly, causing the indexing element  490  of the dose indicator  300  to be displaced downwardly as shown in  FIG. 17 , the rings  460  of the deformable grille element  450  move away from the slots  610  between the rings  590  of the grille element  580  of the display element  320 , thereby significantly reducing the resistance to airflow. The sudden reduction of resistance effectively allows inhalation to start. By this means, the grille elements  450 ,  580  are able to provide a substantial measure of breath-coordination to the user. 
         [0115]    By sucking on the mouthpiece  120  before depressing the container  630 , the user is able to ensure that an inhaled airflow starts as the grille elements  450 ,  580  move apart. Advantageously the pMDI valve releases a dose of medicament while the grille elements  450 ,  580  are moving apart, preferably very soon after the inhaled airflow starts. This coordination of timing essentially ensures that the emitted aerosol of medicament particles is inhaled early in the respiratory manoeuvre of the user and thus reaches the deeper parts of the lungs where the medicament is most effective. As a result, the dose indicator  300  described above also provides a breath-coordination system for a user. 
         [0116]    In alternative embodiments (not shown), the rings of the deformable grille element  450  may be configured never to occlude the slots  610  of the other grille element  580 , and/or bypass air channels can be provided between the chassis element  310  and the actuator  100 , for example in conjunction with a continuous, non-perforated deformable grille element  450 . Such alternative embodiments serve to provide low cost dose indication with minimal changes to the inhaler actuator and a low component count, without breath coordination. 
         [0117]    In a preferred embodiment, the indexing element  490  has a central axis  670  passing through the centre of the central aperture  500  and extending in a direction that is substantially perpendicular to the plane of the deformable grille element  450  as shown in  FIGS. 6 ,  10  to  12  and  15  to  17 . The central axis  670  also provides an alignment reference for the display element  320  within the chassis element  310 , for the deformation of the resilient deformable grille element  450  in the same direction as the translation of the indexing element  490  from a first position ( FIGS. 11 ,  12  and  16 ) to a second position ( FIGS. 15 and 17 ), and for the location of the dose indicator  300  on the stem socket  140  of the nozzle block  130  ( FIG. 1 ). 
         [0118]    As shown in  FIGS. 15 and 17 , the deformation of the resilient deformable grille element  450  forms an inverted frustrum of a cone which is centred about the axis  670 . 
         [0119]      FIGS. 18 to 22  show a second exemplary embodiment of a dose indicator  700  in accordance with the present invention. In general, this exemplary embodiment is similar to the exemplary embodiment described above with reference to  FIGS. 4 to 17  but differs from it in one principal way. In order to provide a greater return spring force than is provided by the deformable grille element  450  alone, the second embodiment has two additional spring arms. In particular, these spring arms are arranged to provide a restorative spring force even when the dose indicator is in its rest position, something which the deformable grille element  450  does not provide. 
         [0120]    It will be appreciated that the resilient deformable grille element  450  of either the first or the second embodiment could be configured to provide a restorative spring force when the dose indicator is in its rest position. However, in such a configuration, it is difficult to ensure that adequate resistance to air is provided in the rest position. This is due to having to mould the resilient deformable grille element  450  in a non-planar form which becomes accurately and reliably planar in the rest position of the dose indicator  300 ,  700 . The deformable grille element  450  needs to be substantially planar when the dose indicator is at rest, in order to provide acceptably high initial resistance to inhaled airflow through the system. 
         [0121]    Components that are the same in both the first and second exemplary embodiments of the dose indicator  300 ,  700  are referenced the same. 
         [0122]      FIG. 21  best shows the additional spring arms  710  (although they are also visible in  FIG. 22 ), which are formed integrally with lid  720 . These arms  710  are configured so that their tips fit into holes  730  provided in the sides of the indexing element  740 . The lower part of the indexing element  740  has wings  745  protruding from diametrically opposite regions. These allow through holes  730  to be formed in the side wall of the indexing element  730  during injection moulding, without the need for side-action tooling. 
         [0123]      FIG. 22  shows the assembled dose indicator  700  of the second exemplary embodiment, showing that the tips (not shown) of the additional spring arms  710  are pushed into the holes  730 . Although not readily evident from this Figure, the two spring arms  710  are downwardly elastically deflected with generally greater downward deflection towards their tips in this rest position of the dose indicator  700 . This deflection causes a resultant upward force to be applied by the spring arms  710  to the indexing element  740 , thereby providing a restorative upward force to the deformable grille element  450 , even in its rest position. 
         [0124]    In  FIGS. 18 to 22 , the indexing element  740  of the dose indicator  700  also has a central axis  670  passing through the centre of the central aperture  500  and extending in a direction that is substantially perpendicular to the plane of the deformable grille element  450 . This central axis provides an alignment reference for the display element  320  within the chassis element  310 , for the deformation of the resilient deformable grille element  450  as it is deformed by translation of the indexing element  740  from a first position to a second position, and for the location of the dose indicator  300  on the stem socket  140  of the nozzle block  130  as described above with reference to the first exemplary embodiment of the dose indicator  300  (see  FIG. 2 ). 
         [0125]    In summary, the first and second exemplary embodiments in accordance with the present invention each provide a simple dose indicator with a ten-dose resolution that counts down inhaler actuations from  200  to zero. Their design is space-efficient and is compatible with inhalers of familiar shape and size to users, and they each require only three additional components compared to a standard pMDI inhaler, thereby meeting the market need for sufficiently low cost. In addition, as shown by the illustrated exemplary embodiments, the design can also, advantageously, incorporate a built-in integrated breath coordination system of the “can&#39;t breathe until press” type. In addition to these advantages and benefits, the dose indicator can clip together as a robust sub-assembly/module, reducing dimensional tolerance issues. The dose indicator may preferably be designed to provide count-before-fire reassurance, in order to minimise the possibility of under-counting. If the user fails to ‘follow through’ to valve actuation after indexing the dose indicator, the dose indicator will indicate fewer doses remain than is actually the case. This is deemed to be safer than the alternative where the user might actuate the valve to dispense a dose but might then fail to follow through to register the count, that is, to index the dose indicator. In that case, the dose indicator might register more remaining doses than is actually the case, leading to a potentially dangerous situation where the user is led to believe they have more doses left than there are in reality. Note that manufacturing tolerances mean that it is never possible to guarantee that valve actuation and dose indicator advancement occur exactly simultaneously in any mechanical system: the choice has to be made which is designed to occur first. 
         [0126]    The three elements of the dose indicator can be cheaply moulded, for example, injection moulded, from “non-engineering grade” polymer, such as a polyolefin such as polyethylene or polypropylene. Polypropylene is preferred as it allows the creation of the living hinge as described above. 
         [0127]    Turning now to a third exemplary embodiment of a dose indicator  800  in accordance with the present invention, reference is made to  FIGS. 23 to 32 . The dose indicator  800  is similar to the exemplary dose indicators  300  described above in that it has a chassis element  810  with a viewing portion  820  through which a portion of a display element  830  can be seen. However, in this embodiment, the chassis element  810  and the display element  830  are the only two components. 
         [0128]    With reference to  FIGS. 25 and 26  in particular, the chassis element  810  comprises a generally rigid outer wall  840 , joined via an upper rim  850  to an inner wall  860 . At multiple, in this embodiment six, locations around the outer wall  840  flexible clips  870  are formed which serve to retain the display element  830  when assembled. The bottom ends  875  of these clips  870  each bear two teeth  880 . Similar teeth  890 , but mounted facing down rather than up, are provided in pairs on the underside of the upper rim  850 , as may be seen in  FIGS. 30 and 31 . Apertures  900  serve to allow injection moulding of the clips  870 . As described above, a viewing portion  820  is provided in the outer wall  840  which aligns with the window  170  ( FIG. 1 ) to enable viewing of the displayed count. As shown in  FIG. 26 , the chassis element  810  also includes a grille element  910  having grille slots  920  formed by rings  930  joined by radial members  935  in a similar way to the grille element  580  of the display element  320 . 
         [0129]    With reference to  FIGS. 27 and 28  in particular, the display element  830  comprises a rigid display ring  940 , on the outer surface of which are provided numerals  945  (not all shown in  FIG. 27 ) corresponding to hundreds, tens and units digits of dose counts. For example, there may be thirteen sets of these numerals, from ‘120’ down to ‘0’ in counts of ten (not all shown in the relevant Figures), arranged anti-clockwise as viewed from the top of the display element  830 . At the bottom of the display ring  940  is provided a set of lower teeth  950  and at the top thereof is provided a set of upper teeth  960 . 
         [0130]    The display ring portion  940  is connected to an indexing element or a central alignment tube  970 , for example, as may be seen more clearly in  FIGS. 30 and 31 , via a flat labyrinthine follow-through spring  980  ( FIG. 28 ). The follow-through spring  980  comprises spring slots  990  which are defined by rings  1000  joined by radial members  1010  as shown. This is similar to the deformable grille element  450  of the first exemplary embodiment of the dose indicator  300  described above with reference to  FIGS. 4 to 17 . 
         [0131]    Protruding downwards from the inside of the display element  830  are three counter spring arms  1020  in the form of three bows, each spring arm  1020  being joined at both ends rather than cantilevered ( FIG. 28 ). These spring arms  1020  press against the actuator running surface  190  ( FIG. 1 ) and bias the upper sets of teeth  890 ,  960  into mutual engagement while separating the lower sets of teeth  880 ,  950  from one another. When the container is pushed downwards by a user, as described above, to release a dose of medicament formulation, the spring arms  1020  flatten out against the running surface  190 , they provide a resistive force that serves to separate the lower sets of teeth  880 ,  950  from one another and to bring the upper sets of teeth  890 ,  960  into mutual engagement to complete a complete unit decrement of the system, when the user subsequently removes their downward pressure on the pMDI canister (not shown) as described above. 
         [0132]    For a typically sized pMDI inhaler, the outside diameter of the display ring  940 , and hence the display element  830 , is approximately 23 mm. For a 120-count display indicator, 132 teeth may typically be provided so as to allow for a few factory advancements/counts during assembly, plus an end-of-count stop feature location, etc. For a 23 mm diameter ring and 132 teeth, each tooth would occupy 360°/132, that is approximately 2.7°, of the circumference, or approximately 0.55 mm. Such teeth are large enough to be reliably injection moulded. As shown in  FIG. 28 , the same number of teeth are provided in the upper set of teeth  960  and the lower set of teeth  950  but the upper set is offset with respect to the lower set. 
         [0133]    It is, however, preferable not to provide all 132 teeth. Instead, as shown in  FIGS. 24 ,  27  and  28 , only alternate teeth are provided in both the upper and lower sets of teeth on the display ring  940 . This has the advantages of being easier to mould (the moulding tooling does not need such fine metal features), and also of avoiding the small dirt traps between teeth that a full set of 132 teeth would create. By having alternate teeth that are offset between the upper set and the lower set, lower frictional forces tend to be experienced. 
         [0134]    As can be seen in  FIGS. 24 and 26 , the teeth  880  on the chassis element  810  are also not immediate neighbours. In this case, two consecutive teeth are “missing”, meaning that the pairs of teeth provided, that is, the bottom teeth  880  on the chassis clips  870 , each comprise teeth that are three positions apart. Because these are an odd number of teeth positions apart, then one of the pair will always be engaged with one of the teeth of the display element  830 . In other words, the display element  830  and the display ring  940  will be rotated by a single increment of approximately 2.7° for each dose taken, even though not all the 132 nominal teeth are present in any of the sets of teeth. Hereafter, where a pitch of one tooth is referred to, it will be understood to correspond to a single increment of the display ring despite any missing teeth. 
         [0135]    As described above with reference to the first exemplary embodiment, the indexing element  970  has an axis (not shown) about which the display ring  830  and the chassis element  810  are arranged. 
         [0136]    The arrangement of the assembled components is as follows. The display element  830  sits in the annular gap between the inner wall  860  and the outer wall  840  of the chassis element  810 , and is held loosely captive by the bottom ends of the clips  870  of the chassis element  810 . The chassis element  810  is, in turn, retained in place near the bottom of the actuator  100  so that it is correctly rotationally aligned and it is prevented from rotational movement relative to the actuator  100 . Appropriate clipping features (not shown) may be provided, for example, undercut clipping features can be moulded into the actuator  100  via moulding tool side-core actions at the mouthpiece  120  and window  170 . The pMDI canister (not shown) is a simple push-fit into the actuator  100 , with a valve stem associated with the valve pushing into the stem socket  140  of the nozzle block  130 . The ferrule of the valve (not shown) is arranged to sit adjacent to the upper end of the central alignment tube or indexing element  970  of the display element  830  in the assembled dose indicator  800 . 
         [0137]    In use, the user actuates the inhaler by pressing down on the pMDI canister (not shown), by squeezing their thumb and finger(s) together against the canister base and the thumb grip  180 . This action tends to push the container of the pMDI canister down relative to the valve stem of the metering valve (not shown), which is restrained in the stem socket  140  of the actuator  100 . As the user continues to press, the ferrule of the valve contacts the central alignment tube or indexing element  970  if the two were not already in contact. As the valve continues to move downwards, it causes the counter spring arms  1020  to flex, these being less stiff than the follow-through spring  980 . As the counter spring arms  1020  flex, they allow the lower teeth  950  of the display ring  940  to engage with the lower teeth  880  of the chassis element  810 , the full engagement of which causes the display element  830  and display ring  940  to rotate by approximately half the pitch of the teeth in a clockwise direction as viewed from above. 
         [0138]    With the teeth now fully engaged, further user depression of the container of the pMDI canister towards the thumb grip  180  does not result in any further motion of the display element  830 , either axially or rotationally, as the engaged lower teeth  880 ,  950  will not allow it. The follow-through spring  980 , however, is able to flex (as will be described later) to allow further ‘follow-through’ motion of the container of the pMDI canister relative to the stem socket  140 . The valve stem (not shown) thus moves further inwardly relative to the rest of the metering valve, and this (in ways familiar to those skilled in the art) causes the valve to dispense a metered dose of medicament formulation out via the bore of the valve stem, into the sump  150 , through the exit orifice  160 , and into the mouthpiece  120 , as shown in  FIG. 32 , for inhalation by the user. 
         [0139]    In this manner, with the counter spring arms  1020  being less rigid than the follow-through spring  980 , ‘count before fire’ is assured, that is, the display element  830  increments before the valve dispenses a dose. Therefore, if the user fails to ‘follow through’ to valve actuation after the display element  830  and display ring  940  has been incremented, the dose indicator will indicate that fewer doses remain than is actually the case. This is deemed to be safer than the alternative where the user might actuate the valve to dispense a dose but might then fail to follow through to register the count, that is, to increment the dose indicator, as described above. 
         [0140]    After receiving the dose, the user then relaxes their grip on the pMDI canister (not shown) and thumb grip  180 . This allows the follow-through spring  980  to start to relax, which in turn allows the weaker counter spring arms  1020  to relax. As the springs relax, the counter spring arms  1020  push the set of lower teeth  950  on the display ring  940  out of engagement with the lower teeth  880  of the chassis element  810  and then push the upper set of teeth  960  into engagement with the upper teeth  890  of the chassis element  810 . The full engagement of the upper teeth  890 ,  960  causes the display element  830  and display ring  940  to rotate by a further approximately half tooth pitch in a clockwise direction as viewed from above. When the user completely releases the system, it has been returned to its starting point except that a dose has been released and the display element  830  and display ring  940  of the dose indicator  810  has now been rotated by the pitch of one tooth in a clockwise direction as viewed from above. A spring (not shown) inside the pMDI metering valve resets the valve, in a manner that will be apparent to one skilled in the art. The numerals  945  displayed in the window  170  of the actuator  100  have thus moved in a downwards-counting direction, for example, from a displayed count of ‘120’ in the direction of ‘110’. 
         [0141]    After this process has been repeated ten times, that is, ten consecutive doses have been dispensed, the displayed numerals will have moved by ten times the pitch of the teeth, corresponding to the distance between sets of numerals  945  on the display ring  940  of the display element  830 . For example, the displayed count might have moved from ‘120’ to ‘110’. As described above, the window  170  is large enough for the user to see up to two sets of numerals, e.g. ‘120’ and ‘110’, so that both are visible when the actual count corresponds to an intermediate number, e.g. ‘116’ or ‘115’. In this manner, the user can observe the shifted position of the display ring  940  and can appreciate that the count has gone from, for example, a hundred and sixteen doses remaining to a hundred and fifteen doses remaining 
         [0142]    Although the display element  830 , and hence the display ring  940 , has been described as being indexed a half pitch on translation of the indexing element from the first position to the second position and a half pitch on the return from the second position to the first position, it will be appreciated that any suitable fraction of the pitch between the teeth can be implemented during the movement from the first position to the second position with the remaining fraction of the pitch being implemented on the return from the second position to the first position. 
         [0143]    At the end of life, that is, a displayed count of ‘0’, an end-of-life stop feature (not shown) would provide a restraint on further dose indicator display rotation. This feature could take several forms, for example, missing teeth, filled in teeth, a raised boss or other feature, etc. 
         [0144]    The third exemplary embodiment in accordance with the present invention provides a simple dose indicator  800  with a ten-dose resolution that counts down inhaler actuations from  120  to zero. The exemplary embodiment provides a dose indicator that can be implemented in a desirably space-efficient manner, allowing for compatibility with pMDI inhalers of familiar shape and size to users, and in particular its design only requires two additional components, thereby meeting the market need for sufficiently low cost. In addition, this exemplary dose indicator also, advantageously, incorporates a built-in integrated breath coordination system of the “can&#39;t breathe until press” type. As described above, the labyrinthine follow-through spring  980  comprises a series of curved spring arms with curved slots  990  between them. When these slots  990  are unobstructed, inhaled air is able to pass through them as it makes its way down between the pMDI canister and the actuator  100  towards the mouthpiece  120  and the lungs (not shown) of a user. 
         [0145]    When the exemplary dose indicator  800  is in its rest position, these slots  990  are adjacent to the curved bars  930  of the grille element  910  provided on the chassis element  810 . 
         [0146]    In this position, the slots  990  are therefore obstructed, so that when the user tries to inhale through the mouthpiece  120 , the resulting high resistance to airflow is uncomfortable and prevents significant respiratory air flow. 
         [0147]    As the user presses down on the base of the pMDI canister in order to deliver a dose, as described above, the central alignment tube or indexing element  970  is pushed down by the pMDI valve (not shown). At first, the display element  830  will tend to translate downwards, for example, from the position shown in  FIG. 29  to that shown in  FIG. 31 . As will be noted, this movement causes the curved arms of the follow-through spring  980  to move away from the slots  920  between the bars  930 ,  935  of the grille element  910 , and the slots  990  in the follow-through spring  980  to move away from the bars of the grille element  910 . In this way, an airflow path of low resistance is opened up through the two sets of slots  920 ,  990 . Further downward movement of the pMDI valve, and hence of the central alignment tube or indexing element  970 , will increasingly cause the centre of the follow-through spring  980  to move down further than its edges, the latter being impeded by engagement of the lower set of teeth  950  of the display ring  940  with the lower set of teeth  880  of the chassis element  810  and by the increasing resistive force from the three counter spring arms  1020  as they flatten out. As the centre of the follow-through spring  980  moves further, to allow actuation of the pMDI valve, the follow-through spring  980  will thus tend to adopt a conical shape (not shown). 
         [0148]    The third exemplary embodiment described herein provides, amongst other features and benefits, a self-contained, integrated dose indicator and breath coordination system for a pMDI inhaler which needs only two extra components compared to a standard pMDI inhaler without a dose indicator or dose counter, and which allows the registering and display of the usage of 120 actuations or more. By using a split-count approach, with partial indicator advancement on the down-stroke, the count decrement being completed on the subsequent up-stroke, advancement of the display ring  940  with respect to the chassis element  810  is ensured. 
         [0149]    It will be appreciated that other split-count approaches may also be implemented which do not require the upper and lower teeth on the display ring  940  and the upper and lower teeth on the chassis element  810 . For example, indexing features may be provided on the inner wall  860  of the chassis element  810  and on the inside of the display ring  940 , for example, the tab or groove arrangements described in U.S. Pat. No. 5,718,355 particularly at column 15, line 64 to column 17, line 19 and in FIGS. 3E to 3H. 
         [0150]    Advantageously, all four sets of teeth are provided by only two components which clip together to form a robust module in which dimensional tolerance issues are substantially reduced. Additionally, the use of the follow-through spring as part of a breath coordination system provides transient flow channel obstruction without incurring cost by having to include additional components. 
         [0151]    The dose indicator of the third exemplary embodiment is designed for count-before-fire reassurance to avoid under-counting of the remaining doses in the associated pMDI inhaler. 
         [0152]    In alternative embodiments (not shown), the curved bars  930  of the grille element  910  may be configured never to occlude the slots  990  of the follow-through spring  980  and/or bypass air channels can be provided between the chassis element  810  and the actuator  100 , for example, in conjunction with a continuous, non-perforated deformable grille element. Such alternative embodiments serve to provide low cost dose indication with minimal changes to the inhaler actuator and a low component count, without breath coordination. 
         [0153]    In addition, there is no need for small teeth to be provided on the display ring which is of particular benefit where the display ring is to be moulded, for example, injection moulded, cheaply from “non-engineering grade” polymer, such as a polyolefin such as polyethylene or polypropylene. 
         [0154]    Although the exemplary embodiments of dose indicators described herein that are integrated with breath coordination functionality utilise a breath coordination system of the “can&#39;t breathe until press” type, other types of breath coordination system, for example, a transient holding chamber for the fired dose, opened upon subsequent user inhalation, could alternatively be used. 
         [0155]    It will be apparent to one skilled in the art that many modifications and variants can be envisaged, without departing from the scope of the present invention. For example, different total numbers of actuations could be indicated, for example, 100 or 50, rather than 120; and colour bands could be used instead of (or in addition to) numerical indications on the display ring. 
         [0156]    Whilst designed to be compatible with most metering valve types, it will be appreciated that minor changes to the profiles and forms of the chassis element and the display element may be necessary to incorporate different valve types. 
         [0157]    The dose indicator in accordance with the embodiments of the present invention can be provided as a sub-assembly for insertion into pMDI inhalers. Alternatively, they could be provided within a separate housing component, as a stand-alone unit, for example for top-mounting on the base of a container of a pMDI canister as an alternative to mounting within the actuator. However, it will be appreciated that in this case, modifications within the skilled person&#39;s normal technical skills, for example, modifications linked to mounting the dose indicator on the base of the container of the pMDI canister, may be needed to ensure that the display ring is correctly indexed. 
         [0158]    It will be appreciated that, although the dose indicators of the present invention have been described for use with an actuator that enables a user to breathe in through his/her mouth, the present invention is also suitable for use in nasal actuators where the mouthpiece can be replaced by a nosepiece.