Abstract:
A medicament delivery device ( 1 ) comprises an actuation mechanism by successive operation of which a predetermined number of unit doses of medicament can be dispensed. The device includes a locking mechanism for preventing further operation of the actuation mechanism after dispensing of said predetermined number of unit doses. The locking mechanism comprises a resilient member ( 51 ), a formation ( 18 ) with which the resilient member ( 51 ) is engageable to disable operation of the actuation mechanism, and a barrier member ( 20 ) that prevents engagement of the resilient member ( 51 ) and the formation ( 18 ) until said predetermined number of unit doses has been dispensed. The device ( 1 ) may be a dry powder inhaler.

Description:
This application is a national phase application under 35 U.S.C. §371 of International Application No. PCT/GB2013/050101, filed Jan. 17, 2013, which claims priority to GB 1201272.0, filed on Jan. 26, 2012, the disclosures of which are all hereby incorporated by reference herein. 
     FIELD OF THE INVENTION 
     This invention relates to improvements to medicament delivery devices, and in particular to mechanisms by which operation of such a device is disabled after a predetermined number of actuations of the device. The mechanisms are of particular utility in relation to devices for the administration of medicaments by inhalation, especially in dry powder inhalers. 
     BACKGROUND 
     The administration of medicaments by inhalation is well-known. A wide variety of medicaments are now administered by that route, for the treatment of a range of respiratory disorders. 
     The most common form in which such medicaments are formulated for administration by inhalation is as a powder. In the past, many such compositions were formulated as pressurised aerosols, in which the powder medicament was suspended in a liquefied propellant. Due to the adverse environmental effects of the propellants conventionally used, however, there is now increased interest in the use of so-called dry powder inhalers (DPIs). In a DPI, a unit dose of medicament powder, either packaged as such or metered from a bulk reservoir of medicament, is presented to an airway and is then entrained in an airflow passing through the airway. The airflow is most commonly generated by the patient&#39;s act of inhalation. 
     DPIs, such as the CLICKHALER® inhaler produced by Innovata. Biomed in the UK and described in EP0539469B, preferably include a dose counter mechanism for providing an indication of the number of doses that have been administered to a patient and/or the number of doses that remain in the inhaler. Conventional dose counter mechanisms for use with DPIs comprise a ratchet mechanism with indicia being carried by the ratchet wheel. 
     WO2005/102430 discloses a dose counter mechanism for a DPI that comprises a tape carrying numbers that are visible at a tape display area. Actuation of the DPI causes the tape to index and a different number to be displayed at the tape display area, thereby giving a visual indication of the number of doses that have been dispensed. 
     Whilst the dose counter mechanism disclosed in WO2005/5102430 is beneficial, further improvement of it would be advantageous. In particular, it would be desirable for the dose counter mechanism to not only indicate to a user of the DPI device the number of doses that have been dispensed (or, alternatively, the number of doses that remain to be dispensed), but also to prevent continued actuation of the device after the last intended dose has been dispensed. Otherwise, a patient may continue to use the device, believing that further doses of medicament are being dispensed when in fact the device is exhausted. 
     SUMMARY OF THE INVENTION 
     There has now been devised an improvement to medicament delivery devices that addresses the above-mentioned need, and/or which overcomes or substantially mitigates the above-mentioned and/or other disadvantages associated with the prior art. 
     According to a first aspect of the invention, there is provided a medicament delivery device comprising an actuation mechanism by successive operation of which a predetermined number of unit doses of medicament can be dispensed, the device including a locking mechanism for preventing further operation of the actuation mechanism after dispensing of said predetermined number of unit doses, characterised in that said locking mechanism comprises a resilient member, a formation with which the resilient member is engageable to disable operation of the actuation mechanism, and a barrier member that prevents engagement of the resilient member and the formation until said predetermined number of unit doses has been dispensed. 
     The medicament delivery device is advantageous primarily in that engagement of the resilient member with the formation prevents further actuation of the device, and so eliminates the possibility of a patient continuing to use the device after the intended number of doses has been dispensed. The resilient member may be biased into engagement with the formation, such engagement being prevented by the barrier member until that number of doses has been dispensed. 
     The medicament delivery device may be an inhaler, and in particular may be a DPI. However, the invention may find utility in other forms of medicament delivery device, eg nasal spray devices and the like. In general, the device may have any form in which a predetermined number of unit doses are dispensed. In some embodiments, the device will include a reservoir in which a bulk quantity of medicament is held, the unit doses being dispensed as aliquots from that bulk quantity. In other embodiments, the device may be loaded with a plurality of discrete unit doses. 
     The device may be used to dispense unit doses of a single medicament. Alternatively, the device may be used to dispense unit doses of a formulation containing two or more medicaments. In a further alternative, the device may be used to dispense unit doses of two or more medicaments from separate reservoirs within the device, those unit doses then being administered to the patient simultaneously. 
     In many embodiments of the device according to the invention, operation of the device is brought about by means of a push-button or the like, which acts upon a dispensing actuator that undergoes a reciprocating motion. By “reciprocating motion” is meant displacement in one direction along a path and then return in the opposite direction along the same path. The path may be linear or have some other suitable form, eg the path may be arcuate or radiussed. 
     In some embodiments, operation of the device not only causes dispensing of a unit dose of medicament (or medicaments), but also operates a dose counting mechanism that provides to the user of the device an indication of the number of doses that have been dispensed (or alternatively the number of doses that remain counter actuator. The dispensing actuator and the dose counter actuator may be integrally formed as a single component. 
     The resilient member may be an elongate arm that is displaced along an axis parallel to the axis of reciprocating movement of the dose counter actuator. The arm may have a projection that in the course of that reciprocating action is brought into registration with the formation, which may be a recess or opening in an adjacent component of the device. The arm is preferably formed integrally with the dispensing actuator. 
     The barrier member may be part of the dose counting mechanism, the barrier member being interposed between the resilient member and the formation until the last of the predetermined number of unit doses has been dispensed. Operation of the device to dispense the last of the predetermined doses may have the effect of removing the barrier member from between the resilient member and the formation, thereby permitting the resilient member to engage the formation and preventing further operation of the device. 
     In some embodiments, the device incorporates a dose counting mechanism in which indicia showing the number of doses dispensed or remaining are carried on an element that is displaced upon each actuation. That element may constitute the barrier element. The indicia may be numbers or may be some other visual indication of the number of doses dispensed or remaining, eg a graduation in pattern or colour. 
     In currently preferred embodiments of the invention, the dose counting mechanism comprises a tape that carries indicia showing the number of doses dispensed or remaining. The tape is wound on a take-up spool and is indexed upon each actuation of the device. The tape may pass between the resilient member and the formation during at least part of the actuation process, and may thereby prevent engagement of the resilient member with the formation. The tape may thus constitute the barrier member. 
     The tape may be configured such that once the predetermined number of unit doses has been dispensed it ceases to act as a barrier between the resilient member and the formation. For instance, the tape may have a length such that an end of the tape clears the area between the resilient member and the formation once the last of the predetermined number of doses has been dispensed. More preferably, however, the tape is formed with an opening, a puncture or an area of weakness that is brought into registration with the formation upon dispensing of the last of the predetermined doses, thereby removing the barrier between the formation and the resilient member and allowing the formation and the resilient member to engage. The tape may, for instance, have an opening (square, rectangular, circular, elliptical or any other suitable shape) formed in it. 
     Alternatively, the tape may have one or more slits formed in it, such that the resilient member is able to penetrate the tape in the region of the slit(s). In a currently particularly preferred arrangement, the tape is formed with an axial slit that is intersected by one or more transverse slits. 
     Engagement of the resilient member with the formation preferably prevents further movement of the dispensing actuator. In some preferred embodiments, the resilient member engages the formation when the dispensing actuator is in its depressed position. As the dispensing actuator will normally be biased to the opposite extent of its travel, this provides an immediate visual indication that the device has been exhausted (ie that the predetermined number of doses has been dispensed). 
     Thus, according to another aspect of the invention, there is provided a medicament delivery device comprising a dispensing actuator by successive operation of which a predetermined number of unit doses of medicament can be dispensed, the device including a locking mechanism for preventing further operation of the dispensing actuator after dispensing of said predetermined number of unit doses, and the dispensing actuator being capable of reciprocating motion between a rest position and a depressed position, the dispensing actuator being biased to the rest position and after dispensing of said predetermined number of unit doses being locked in the depressed condition. 
     The locking mechanism may form part of a dose counting mechanism of the kind disclosed in WO2005/102430. Such a mechanism comprises a tape carrying numbers that are visible at a tape display area, the tape being held in a tape dispenser housing with a tape collector spool. Actuation of the device causes the tape to index and a different number to be displayed at the tape display area, thereby giving a visual indication of the number of doses that have been dispensed (or the number that are remaining). 
     The tape may be formed of a plastics material. The indicia are preferably printed on a surface of the tape, and preferably take the form of a series of numbers that indicate either the number of doses administered or the number of doses remaining within the medicament delivery device. 
     The tape dispenser housing preferably comprises an enclosure within which a roll of the tape is housed, and an opening through which the tape exits the tape dispenser housing. Most preferably, the tape dispenser housing has an opening that is sufficiently large for the roll of tape to be introduced into the tape dispenser housing, but is configured so as to retain the roll of tape within the tape dispenser housing, during use. In preferred embodiments, the tape dispenser housing comprises an enclosing wall having a generally C-shaped cross-section, and end flanges that prevent any lateral movement of the roll of tape. 
     It is particularly preferred that the tape that is held in the tape dispenser housing is formed into a simple roll, without being wound on a bobbin or the like. 
     The tape display area preferably has a smooth and generally flat surface that the tape overlies in use, at least one of the indicia provided on the part of the tape overlying the tape display area preferably being visible to a user. The tape may be indicia. In this case, the tape display area is preferably coloured distinctly relative to the colour of the indicia. 
     The collector spool is preferably rotatably mounted within a collector spool housing. The dispenser housing, the collector spool housing, and the tape display area are preferably formed as a single component, preferably by injection moulding in a plastics material. 
     A retaining clip is preferably also provided to ensure that the tape is sufficiently taut for the indicia to be readily visible and for the movement of the tape in use to be precise enough to ensure accurate counting of the doses. The retaining clip may also act to ensure that the tape lies flat against the tape display area during use, and to assist in retaining the roll of tape within the tape dispenser housing. 
     The dose counter mechanism preferably includes a dose counter actuator that acts to rotate the collector spool appropriately during use. In particular, the dose counter actuator preferably rotates the collector spool by a pre-determined degree each time a dose of medicament is dispensed from the medicament delivery device. Most preferably, this rotation of the collector spool by a pre-determined degree each time a dose of medicament is dispensed from the medicament delivery device causes the indicia visible to the user to change, preferably to an adjacent indicia provided on the tape. The dose counter actuator is therefore preferably operably linked to the dispensing actuator. Most preferably, the dose counter actuator and the dispensing actuator are integral with each other. 
     Where the dispensing actuator is displaced along a linear path and then returned to its rest position each time a dose of medicament is dispensed, the dose counter actuator is also preferably displaced along a linear path and then returned to its rest position each time a dose of medicament is dispensed. The dose counter actuator is therefore preferably adapted to rotate the collector spool by a predetermined degree on being displaced along a linear path and then returned to its rest position. 
     In some embodiments, the collector spool comprises an end plate having a plurality of projections that are engageable by the dose counter actuator, during use, to cause rotation of the collector spool. Preferably, the projections are spaced equi-angularly about a peripheral part of the end plate. 
     The dose counter actuator preferably comprises first and second actuator arms, the first actuator arm engaging the collector spool when the dose counter actuator is displaced from its rest position, and the second actuator arm engaging the collector spool on the return stroke of the dose counter actuator to its rest position. Most preferably, the second actuator arm is engaged with a projection when the dose counter actuator is in its rest position, and the first actuator arm engages a projection upon displacement of the dose counter actuator from its rest position, which then causes the first actuator arm to exert a force on the projection with which it is engaged so as to rotate the collector spool. The second actuator arm engages a projection on the return stroke of the dose counter actuator. The first and second actuator arms thus engage projections on opposite sides of the axis of rotation of the collector spool. In this way, the collector spool is rotated by the movement of the dose counter actuator and rotation of the collector spool in the reverse direction is prevented. 
     The medicament delivery device is preferably an inhaler, and more preferably a DPI, such as the CLICKHALER® inhaler produced by Innovata Biomed in the UK and described in EP0539469B or the combination therapy DPI described in WO01/39823. 
     A variety of medicaments may be administered using the inhaler of the invention. Such medicaments are generally suitable for the treatment of asthma, COPD and respiratory infections. Such medicaments include, but are not limited to β 2 -agonists, eg fenoterol, formoterol, pirbuterol, reproterol, rimiterol, salbutamol, salmeterol and terbutaline; non-selective beta-stimulants such as isoprenaline; xanthine bronchodilators, eg theophylline, aminophylline and choline theophyllinate; anticholinergics, eg ipratropium bromide, oxitropium and tiotropium; mast cell stabilisers, eg sodium cromoglycate and ketotifen; bronchial anti-inflammatory agents, eg nedocromil sodium; and steroids, eg beclomethasone, fluticasone, budesonide, flunisolide, triamcinolone, mometasone and ciclesonide; and/or salts or derivatives thereof. 
     Specific combinations of medicaments which may be mentioned include combinations of steroids and β 2 -agonists. Examples of such combinations are beclomethasone dipropionate and formoterol; beclomethasone dipropionate and salmeterol; fluticasone and formoterol; fluticasone and salmeterol; budesonide and formoterol; budesonide and salmeterol; flunisolide and formoterol; flunisolide and salmeterol; ciclesonide and salmeterol; ciclesonide and formoterol; mometasone and salmeterol; and mometasone and formoterol. 
     Further medicaments which may be mentioned include systemically active materials, such as proteinaceous compounds and/or macromolecules, for example hormones and mediators, such as insulin, human growth hormone, leuprolide and alpha interferon, growth factors, anticoagulants, immunomodulators, cytokines and nucleic acids. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       One embodiment of the invention will now be described in greater detail, by way of illustration only, with reference to the accompanying drawings, in which 
         FIG. 1  is a perspective view of a dry powder inhaler device according to the invention; 
         FIG. 2  shows a tape housing, a tape, and a retaining clip, which together form part of a dose counter mechanism that forms part of the device of  FIG. 1  and incorporates a device locking mechanism according to the invention; 
         FIG. 3  is a perspective view of the tape housing, tape, and retaining clip of the dose counter mechanism, as well as a collector spool that also forms part of the dose counter mechanism, in an assembled configuration; 
         FIG. 4  is a side view of a dose counter actuator that forms part of the dose counter mechanism; 
         FIG. 5  is a view of part of the dose counter actuator in engagement with the collector spool, when the dose counter actuator is in the rest configuration; 
         FIG. 6  is a view similar to that of  FIG. 5 , but when the dose counter actuator is in a depressed configuration; 
         FIG. 7  is a sectional view illustrating the interaction of a locking arm that forms part of the dose counter actuator with the dose counter mechanism, when the dose counter actuator is in the rest configuration; 
         FIG. 8  is a view similar to  FIG. 7 , but with the dose counter actuator in the depressed configuration; 
         FIG. 9  is a view similar to  FIGS. 7 and 8 , but showing the dose counter actuator in a locked configuration, after dispensing of the final dose of medicament from the inhaler; 
         FIG. 10  shows the part of the tape with an opening that permits locking of the dose counter in the manner illustrated in  FIGS. 7 to 9 ; and 
         FIG. 11  shows an alternative form of tape with an arrangement of slits to permit locking of the dose counter. 
     
    
    
     DETAILED DESCRIPTION 
     Referring first to  FIG. 1 , a dry powder inhaler is generally designated  1  and comprises a body  2  with an integral mouthpiece that is covered by a removable cap  3 . The upper (as viewed in  FIG. 1 ) part of the inhaler  1  comprises a depressible push-button  4 . The inhaler  1  includes a dose dispensing mechanism (not visible) that is broadly as described in EP1233805B. The inhaler  1  further comprises a dose counter mechanism that incorporates a device locking mechanism according to the invention, which prevents further actuation of the device once a predetermined number of actuations of the device have occurred and which is described below. 
     Referring now to  FIGS. 2 to 4 , the dose counter mechanism comprises a tape housing  10 , a tape  20 , a retaining clip  30 , a collector spool  40 , and an actuator  50  that combines the functions of a dispensing actuator and a dose counter actuator. The actuator  50  includes an integral locking arm  51 , the operation of which is described in detail below. 
     The tape housing  10  is injection moulded in plastics material as a single component, and is shown in  FIG. 2 . The tape housing  10  comprises a side wall  11  that is adapted to be attached to a relevant part of the dry powder inhaler  1 . Extending from one side of the side wall  11  is a first member  12  having a generally radiussed upper surface (as viewed in FIG.  2 ), and a second member having a rear wall  13 , a dispenser housing  14 , a tape display plate  15 , and a collector spool housing  16 . A small gap exists between the underside of the first member  12  and the upper edge of the rear wall  13 . 
     A generally square opening  18  is formed in the rear wall  13  of the tape housing  10 . 
     The rear wall  13  is orientated substantially along the longitudinal axis of the tape housing  10 , and is situated slightly below and rearward (as viewed in  FIG. 2 ) of the first member  12 . The dispenser housing  14  extends from the lower end of the rear wall  13 , and comprises a front enclosing wall of C-shaped cross-section and a C-shaped end flange. An opening is therefore defined at the rear of the dispenser housing  14 . In an assembled configuration, the dispenser housing  14  holds a roll of tape  20 , and the end flange prevents any lateral movement of the roll of tape  20 , during use. 
     A tape display plate  15  extends from a lower part of the dispenser housing  14  to the collector spool housing  16  at the lower end of the tape housing  10  (as viewed in  FIG. 2 ). The front surface of the tape display plate  15  is smooth and generally flat. The smooth and generally flat nature of the front surface of the tape display plate  15  enables the tape  20  to be presented to a user in an easily readable configuration. 
     The collector spool housing  16  is cylindrical in form with one end extending from the side wall  11  of the tape housing  10 , and the other end being open. A slot  17  is provided in the wall of the collector spool housing  16  through which the tape  20  enters before being wound on the collector spool  40  (part of which is visible in  FIG. 3 ). The surface defining the upper edge of the slot  17  is rounded. 
     The tape  20  is shown in  FIG. 2  in a configuration that the tape  20  adopts when assembled within the dose counter mechanism. The tape  20  is a transparent plastics film with a series of numbers (not shown), from zero to a number that indicates the number of doses contained within the fully charged dry powder inhaler  1 , printed on a surface of the tape  20 . The tape  20  is in the form of a roll  24  with the numbers printed in a colour that is clearly visible against the background formed by the tape display plate  15 . The tape is simply formed into the roll  24 , which is then inserted into the dispenser housing  14 . 
     The retaining clip  30  is formed from a resilient metal, such as stainless steel, and has the form shown in  FIG. 2 . In particular, the retaining clip  30  comprises a front retainer  31 , a rear retainer  32 , and a connecting portion  33 . The front and rear retainers  31 ,  32  each include a pair of parallel arms that are planar in form and adapted to overlie the outer surface of the tape  20  in the assembled dose counter mechanism. The lower ends (as viewed in  FIG. 2 ) of the arms of the front and rear retainers  31 ,  32  are outwardly turned. The connecting portion  33  comprises three parallel members. The outer two members of the connecting portion  33  connect the front and rear retainers  31 ,  32 , and are shaped to conform to the radiussed upper surface of the first member  12 . The central member of the connecting portion  33  has the form of a clip that engages the first member  12  in the assembled configuration of the dose counter mechanism. 
       FIG. 3  shows the tape housing  10 , tape  20 , retaining clip  30 , and collector spool  40  in an assembled configuration. The roll of tape  20  is held within the dispenser housing  14  by the rear retainer  32  of the retaining clip  30 . The tape  20  extends from the dispenser housing  14 , along the rear surface of the rear wall  13 , through the gap between the first member  12  and the upper edge of the rear wall  13 , along the front surface of the tape display plate  15 , through the slot  17 , and into the collector spool housing  16 . The retaining clip  30  is engaged with the first member  12  so as to maintain the tape  20  in a relatively taut state, to urge the tape  20  against the front surface of the tape display plate  15 , as well as preventing displacement of the roll of tape from the dispenser housing  14  and providing uniform tension in the tape  20  to ensure accurate counting of the doses. The tape  20 , in passing along the rear surface of the rear wall  13 , occludes the opening  18  in the rear wall  13 . 
     The collector spool  40  comprises an end plate  42  that is in abutment with the open end of the collector spool housing  16 , and a cylindrical shaft (not visible in  FIG. 3 ) housed within the collector spool body  16 , the end of which engages in an opening in the side wall  11  of the tape housing  10  such that the collector spool  40  can rotate. The tape  20  enters the collector spool housing  16  through the slot  17 , and is guided by the surface of the collector spool housing  16  that defines the upper edge of the slot  17  onto the collector spool  40 . The end of the tape  20  is fixed to the collector spool  40  such that rotation of the collector spool  40  in a clockwise direction (as viewed in  FIGS. 2 and 3 ) winds the tape onto the cylindrical body of the connector spool  40 . 
     The end plate  42  has the form of a D-shaped disc, with three pegs  44  provided on the outwardly-facing surface of the end plate  42 . The three pegs  44  are spaced equi-angularly about a peripheral part of the outwardly-facing surface of the end plate  42 , and each peg  44  comprises a cylindrical neck and an enlarged head. 
     In the fully charged inhaler  1 , the dose counter mechanism is assembled such that the majority of the tape  20  is held in the dispenser housing  14  in the form of a roll  24 . As described above, the tape  20  extends along the front surface of the tape display plate  15 , and the end of the tape  20  is fixed to the collector spool  40 . In this configuration, the printed number that indicates the number of doses contained within the fully charged dry powder inhaler is located over a viewing part of the tape display plate  15 . The inhaler  1  has a transparent window (not visible in  FIG. 1 ) that overlies the viewing part of the tape display plate  15 , such that this printed number is visible to the user. 
     To dispense a dose of medicament from the inhaler  1 , the user depresses and releases the push-button  4 , which is connected to the dose counter actuator  50  of  FIG. 4 . The actuator  50  is spring-loaded so that it (and the push-button  4 ) returns to its rest configuration once released by the user. 
     Each depression and release of the actuator  50  causes the collector spool  40  to be rotated through 120°, thereby causing a pre-determined length of the tape  20  to be wound onto the collector spool  40 . This, in turn, causes the tape  20  to be advanced along the tape display plate  15 , such that the next printed number in the series is located over a viewing part of the tape display plate  15  and hence is visible through the transparent window of the inhaler  1 . 
     This action is achieved by virtue of the form of the actuator  50 , as shown in  FIG. 4 . The actuator  50  comprises an upstand  52  that is operably linked to the push-button  4 , such that the dose counter actuator  50  is displaced downwardly (as viewed in  FIG. 4 ) when the push-button  4  is depressed, and is returned to its rest position when the push-button  4  is released. 
     The actuator  50  also has a portion that engages the end plate  42  of the collector spool  40  so as to effect rotation of the collector spool  40  on depression and release of the push-button  4 , as discussed above. This portion comprises downwardly-extending first and second actuator arms  54 ,  56 , each with an arcuate engagement member  55 , 57  at its lower end for engaging a peg  44  of the end plate  42 . In particular, the engagement member  55  of the first actuator arm  54  is adapted to engage the upper surface of a peg  44 , pushing that peg  44  downwards, and the engagement member  57  of the second actuator arm  56  is hooked, so as to engage the lower surface of a peg  44 . 
     The first and second actuator arms  54 ,  56  are shown in  FIGS. 5 and 6  in engagement with the end plate  42  of the collector spool  40 . Before depression of the push-button  4 , and downward displacement of the dose counter actuator  50 , the second actuator arms  56  engages a peg  44  of the end plate  42 , as shown in  FIG. 5 . In particular, the engagement member  57  of the second actuator arm  56  is in engagement with the lower surface of a peg  44  on the left-hand side of the end plate  42  (as viewed in  FIG. 5 ). 
     Depression of the push-button  4 , and hence downward displacement of the dose counter actuator  50 , causes the engagement member  55  of the first actuator arm  54  to engage the upper surface of the peg  44 , and urge that peg  44  downwards. This causes the endplate  42 , and hence the collector spool  40 , to rotate in a clockwise direction. The engagement member  57  of the second actuator arm  56  will be displaced downwardly by this action ( FIG. 6 ), freeing it from the peg  44  with which it was in contact. 
     Release of the push-button  4 , and hence upward displacement of the actuator  50 , will cause the engagement member of the second actuator arm  56  to return to its rest position, at which it engages a peg  44  from below, thereby holding the endplate  42 , and hence the collector spool  40 , in the position to which it has been rotated. The arrangement is then once again as shown in  FIG. 5  (but with the engagement members of the second actuator arm  56  engaged with a different peg  44 ). 
     Operation of the actuator  50 , by depression of the push-button  4 , also of course causes a dose of medicament (or medicaments) to be dispensed. The manner in which this is achieved is specific to the dry powder inhaler of which the dose counter mechanism forms part, but may be as described in EP1233805B. 
     As described above, each depression and release of the push-button  4  will cause a dose of medicament to be dispensed, and the collector spool  40  to rotate 120° so that the next number in the series of numbers printed on the tape  20  is visible to the user. 
     As noted above, the dose counter mechanism incorporates a device locking mechanism. The manner in which this operates is illustrated in  FIGS. 7 to 9 . 
     Referring first to  FIG. 7 , when the actuator  50  is depressed from, and then returns to, its rest configuration, the locking arm  51  reciprocates adjacent to the portion of the tape  20  that is supported by the rear wall  13  of the tape housing  10 . The tip of the locking arm  51  is bifurcated, having a projection  51   a  that projects towards the tape  20 . 
     As shown in  FIG. 8 , in the downward stroke of the actuator  50 , the projection  51   a  bears against the tape  20 , with the result that the locking arm  51 , which is somewhat resilient, is slightly deflected. At the lowest extent of its travel, the projection  51   a  is disposed adjacent to the opening  18  in the rear wall  13  of the tape housing  10 . However, the tape  20  occludes the opening  18 , so that the projection  51   a  rides over the tape  20  and the movement of the projection  51   a  is not interfered with by the opening  18 . 
     As shown in  FIGS. 9 and 10 , however, a slot  21  is formed in the tape  20 . The slot  21  is positioned in the tape  20  such that the slot  21  comes into registration with the opening  18  when the last of the predetermined number of actuations of the inhaler  1  has occurred. 
     In the configuration depicted in  FIG. 8 , the slot  21  is positioned below the opening  18  (and so is not visible in  FIG. 8 ). Further actuation of the device, however, brings the slot  21  to the position shown in  FIG. 9 , where the slot  21  is aligned with the opening  18 . Instead of the locking arm  51  returning towards its rest configuration ( FIG. 7 ) following that actuation, the resilience of the locking arm  51  causes the projection  51   a  to pass through the slot  21  and to engage the opening  18 . The travel of the actuator  50  back to its rest configuration is thereby arrested, locking the actuator  50  in its depressed condition. Further operation of the device is thereby prevented and it is impossible for the user to continue to use the device. 
     Finally,  FIG. 11  shows an alternative tape  20   a . In this embodiment, the tape  20   a  is not formed with an opening, but with an arrangement of slits including an axial slit  21   a  that intersects with four shorter transverse slits  21   b . The effect of these slits  21   a ,  21   b  is to permit the projection  51   a  to penetrate through the tape  20   a  when the slits  21   a ,  21   b  come into registration with the opening  18 . The slits  21   a ,  21   b  thus function in the same manner as the opening  21  of the tape  20  of  FIG. 10 . However, this embodiment offers the advantage that no material is cut from the tape  20   a  during manufacture and no fragments of tape material are created that could potentially contaminate the device and/or be inhaled by a user of the device.