Abstract:
Provided herein are dry powder inhalers for the delivery of metered doses of medicament, counters associated with the inhalers for counting and displaying the number of doses administered or remaining within the inhaler, and methods of use thereof.

Description:
FIELD OF THE INVENTION  
         [0001]    This invention concerns dry powder inhalers for the delivery of metered doses of medicament, and counters associated with the inhalers for counting and displaying the number of doses administered or remaining within the inhaler.  
         BACKGROUND OF THE INVENTION  
         [0002]    Oral delivery of medicaments to treat disorders such as asthma, emphysema and chronic bronchitis has been, for many years, reliably and effectively accomplished through the use of pressurized metered dose inhalers (PMDIs). Such inhalers provide a stream of atomized medicament inhaled directly into the affected air passageways and lungs to afford rapid relief from the symptoms of such disorders.  
           [0003]    As an alternative to PMDIs, dry powder inhalers (DPIs) have received considerable attention because of their propellant-free composition and their relative ease of operation compared to PMDIs. DPIs can be used for oral and nasal administration and may be presented with the drug formulation pre-metered as capsules (unit-dose inhaler), blisters and cartridges (multi-unit dose inhaler) or as bulk material in a reservoir (multi-dose inhalers).  
           [0004]    A necessary design feature of PMDIs and multi-dose DPIs is that they contain more formulation than strictly required to expel the labeled number of actuations/doses. A potential problem which may be particularly acute for PMDIs is dose inconsistency beyond the labeled number of actuations/doses. A patient unknowingly using a PMDI or multi-dose DPI beyond the recommended number of doses may risk not receiving the correct drug dose with possibly dangerous consequences.  
           [0005]    To avoid this problem, it is desirable to include a counter integrally with the inhaler to count and display to the user the number of doses remaining within the inhaler. This will allow the user sufficient warning as to when the inhaler is running low and should, therefore, be replaced so as to avoid the potential for sub-therapeutic dose administration. The counter should be simple in design, reliable in operation and easy to read and interpret.  
         SUMMARY AND OBJECTS OF THE INVENTION  
         [0006]    The invention concerns a dry powder inhaler for administering a metered dose of a medicament to a user. The inhaler comprises a reservoir holding the medicament and an air channel assembly engaged with and movable relatively to the reservoir for receiving the dose of medicament upon the relative motion. The medicament is administered when the user draws a breath through the air channel assembly; the medicament, in powdered form, being entrained in the air drawn through the air channel assembly and into the user&#39;s air passageways.  
           [0007]    The inhaler also comprises a counter for counting the number of doses dispensed from the reservoir or the number of doses that can still be delivered before the device is considered empty. The counter comprises a first indicator member which moves one increment in response to the motion of the air channel assembly relative to the reservoir. The increment of movement corresponds to each dose dispensed from the reservoir. The counter also has a second indicator member which moves intermittently in response to motion of the first indicator member. Both indicator members have indicia thereon for displaying the number of doses dispensed from the reservoir or the number of doses that can still be delivered before the device is considered empty. A rotatory intermittent drive transfer mechanism is positioned between, and engaged with, the first and second indicator members. In operation, the first indicator member drives the rotatory intermittent drive transfer mechanism and the rotatory intermittent drive transfer mechanism drives the second indicator member intermittently upon motion of the first indicator member. Preferably, the first indicator member is a unit wheel. Preferably, the second indicator member moves one increment for every ten increments of the unit wheel (hereinafter a “tens” wheel), and the indicia thereon represent tens of doses, whereas the indicia on the unit wheel represent unit doses. Also, it is foreseeable that the inhaler comprise a third, and optionally fourth, indicator member. The third indicator member can move one increment for every 100 increments of the tens wheel (hereinafter a “hundreds” wheel), and the indicia thereon represent hundreds of doses. The fourth indicator member can move one increment for every 1000 increments of the hundreds wheel (hereinafter a “thousands” wheel), and the indicia thereon represent thousands of doses.  
           [0008]    Preferably, the reservoir is arranged circumferentially around a central axis and the air channel assembly is positioned coaxially with the reservoir and rotatably movable about the central axis relatively thereto. The first and second indicator members are also preferably positioned coaxially with the reservoir and rotatably movable about the central axis for counting the doses dispensed from the reservoir or the number of doses that can still be delivered before the device is considered empty.  
           [0009]    The unit wheel has a first surface on which the counting indicia representing unit doses appear, the first surface facing radially outwardly from the central axis. The tens wheel has a second surface on which the indicia representing tens of doses appear, the second surface being transparent and facing radially outwardly from the central axis. The unit wheel is preferably nested within the tens wheel and the indicia on the unit wheel juxtapose with the indicia on the tens wheel and are visible through the transparent surface of the tens wheel to display the number of the doses dispensed from the reservoir or the number of doses that can still be delivered before the device is considered empty.  
           [0010]    As noted above, the unit and tens wheels are connected by a rotatory intermittent drive transfer mechanism which imparts intermittent motion to the tens wheel upon motion of the unit wheel. Preferably, the rotatory intermittent drive transfer mechanism comprises a slave wheel rotatable about an offset axis offset from the central axis and substantially parallel thereto. The slave wheel has a drive transfer wheel on one face and a gear on the opposite face. Preferably, the unit wheel has a foot extending therefrom for engaging the drive transfer wheel, and the tens wheel has gear teeth arranged around its interior surface circumference for meshing with the gear on the opposite face of the slave wheel. Upon a predetermined number of incremental movements of the unit wheel (preferably 10), the foot on the unit wheel engages with the drive transfer wheel and causes the slave wheel to rotate, whereupon the gear teeth on the slave wheel engage and rotate the tens wheel one increment. It is preferred that the gear and drive transfer wheel are situated in the interior circumference, so that the drive transfer mechanism is able to drive the unit and tens wheel in the same direction. However, it is also foreseeable that by using interior and exterior drive transfer wheels and gears, the drive transfer mechanism is able to drive the unit and tens wheel in the opposite direction to each other. Also, it is foreseeable that by changing the gear ratio, the total number of doses that can be displayed by the counter can also be changed.  
           [0011]    The slave wheel may incrementally rotate the tens wheel intermittently in response to rotation of the unit wheel in accordance with the following preferred embodiment. Thus, the unit wheel has an inwardly facing circumferential surface with a notch therein. The foot, which extends from the unit wheel, is positioned adjacent to the notch. The drive transfer wheel, positioned on a face of the slave wheel facing the unit wheel, has a plurality of receptacles spaced circumferentially therearound, each for receiving the foot on the unit wheel. A rotation-preventing feature is embodied in a plurality of outwardly extending lobes positioned between the drive transfer wheel and the gear on the slave wheel. Each of the lobes is aligned with a respective receptacle on the drive transfer wheel, one or more of the lobes engaging the inner circumferential surface of the unit wheel as the unit wheel rotates, thereby preventing inadvertent rotation of the slave wheel and, thus, the tens wheel. One lobe of the slave wheel is received within the notch in the inner circumferential surface of the unit wheel when the foot of the unit wheel engages one of the receptacles on the drive transfer wheel aligned with the lobe to rotate the slave wheel. The notch provides clearance between the lobe and the inner circumferential surface of the unit wheel, allowing the slave wheel to incrementally rotate, thereby rotating the tens wheel. Another of the lobes then engages the inner circumferential surface of the unit wheel upon incremental rotation of the slave wheel, thereby again preventing rotation of the slave wheel until the foot on the unit wheel again engages the next one of the receptacles, aligned with the next lobe, on the drive transfer wheel.  
           [0012]    It is an object of the invention to provide an inhaler with a counter for counting the doses dispensed from the inhaler or the number of doses that can still be delivered before the device is considered empty.  
           [0013]    It is a further object of the invention to provide a counter actuated by rotary motion of a component of the inhaler.  
           [0014]    It is another object of the invention to provide a counter having a first indicator member (e.g. a unit wheel) which intermittently drives a second indicator member (e.g. a tens wheel) through a rotatory intermittent drive transfer mechanism.  
           [0015]    It is yet another object of the invention to provide a counter, wherein the first indicator member (e.g. a unit wheel) is coaxially nested within the second indicator member (e.g. a tens wheel).  
           [0016]    It is still another object of the invention to provide a counter, wherein the rotatory intermittent drive transfer mechanism provides a locking feature preventing undesired motion of the tens wheel.  
           [0017]    It is again another object of the invention to provide a rotatory intermittent drive transfer mechanism comprising a slave wheel with a drive transfer wheel on one face and a gear on the opposite face.  
           [0018]    It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Also, various features of the invention which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination.  
           [0019]    These and other objects and advantages of the invention will become apparent upon consideration of the following drawings and detailed description of preferred embodiments of the invention. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0020]    [0020]FIG. 1 is a perspective view of the inhaler according to the invention;  
         [0021]    [0021]FIG. 2 is an exploded perspective view of the inhaler shown in FIG. 1;  
         [0022]    [0022]FIG. 3 is a partial exploded perspective view showing the counter for the inhaler;  
         [0023]    [0023]FIG. 4 is an exploded partial sectional view of the counter and the base of the inhaler;  
         [0024]    [0024]FIG. 4A is a partial sectional view of the counter and the base of the inhaler with the counter assembled and mounted on the inhaler;  
         [0025]    [0025]FIG. 5 is a cross-sectional view taken along lines  5 - 5  in FIG. 4A;  
         [0026]    [0026]FIG. 6 is a cross-sectional view taken along lines  6 - 6  in FIG. 4A showing the unit wheel and geneva mechanism in a cooperating position to advance the tens wheel;  
         [0027]    [0027]FIG. 7 is a cross-sectional view taken along lines  6 - 6  in FIG. 4A showing the geneva mechanism in a locked position to prevent advancement of the tens wheel; and  
         [0028]    [0028]FIG. 8 is a cross-sectional view taken along lines  8 - 8  in FIG. 4A. 
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0029]    By way of example only, a geneva mechanism, which intermittently transfers the drive from one element to another via geneva wheel, is described below, it being understood that any intermittent drive transfer mechanism incorporating an intermittent drive transfer wheel, works essentially the same way and could be used in the claimed invention.  
         [0030]    [0030]FIG. 1 is a perspective view of a preferred embodiment of an inhaler  10  according to the invention. FIG. 2 is an exploded view of the inhaler  10  shown in FIG. 1. Moving downwardly and from left to right in FIG. 2, the inhaler comprises a dust cap  12 , an air channel assembly  14 , a medicament reservoir  16  for holding a powdered medicament (not shown) and a barrel  18 . The air channel assembly  14  comprises a mouthpiece  20 , a collar  22 , a reservoir  16 , and a drive sub-assembly  112 . Drive sub-assembly  112  fits coaxially within barrel  18 , and the reservoir  16  of air channel assembly  14  fits coaxially within the drive sub-assembly  112 . Collar  22  and mouthpiece  20  on the end of the air channel assembly  14  extend outwardly from the reservoir  16  and barrel  18  to engage the lips of a user as described below.  
         [0031]    A counter  26  is mounted onto the inhaler  10  on the end of barrel  18  opposite the dust cap  12 . Counter  26  comprises a coupling  28 , a unit wheel  30 , a slave wheel  32 , a tens wheel  34  and a cover  36  in which the unit wheel  30 , slave wheel  32  and tens wheel  34  are rotatably mounted. Cover  36  has a window  38  therein through which indicia  40  and  42 , printed on the unit and tens wheels respectively, may be viewed, indicating the number of doses that can still be delivered before the medicament reservoir  16  is considered empty or the number of doses dispensed therefrom.  
         [0032]    As shown in detail in FIG. 2, cover  36  of counter  26  has a bottom  44  which supports the tens wheel  34  for rotational motion about a central axis  46 . Tens wheel  34  has an inwardly extending flange  48  which is sized to surround and engage a raised boss  50  positioned on the bottom  44  concentric with the central axis  46  (see also FIGS. 4 and 4A). Cooperation between the flange  48  and the boss  50  keeps the tens wheel  34  concentric within the cover  36  and allows guided rotation of the tens wheel about the central axis  46 . Bottom  44  also has a circular groove  52  positioned concentric with the central axis. The groove  52  is sized to accept a tab  54 , best shown in FIG. 3. The tab  54  extends downwardly from the tens wheel  34  and tracks within the groove  52  as the tens wheel rotates about central axis  46 . As shown in FIG. 2, a stop block  56  is positioned within the groove  52 . When the tens wheel  34  has rotated such that the last of the series of indicia has been displayed in the window  38 , the stop block  56  engages the tab  54  to halt its rotation and thereby preventing the counter from resetting itself after it has counted down to zero and thus give a false reading of the number of doses remaining in the inhaler. Also, when incrementing the counter it is foreseeable that the stop block&#39;s  56  ability to engage the tab  54  to halt its rotation would also prevent the counter from resetting itself when the last of the series of indicia has been displayed in the window  38 .  
         [0033]    As shown in FIGS. 2 through 4A, an outwardly facing sidewall  58  on the cover  36  extends circumferentially around the bottom  44  and is attached to the end of barrel  18  to enclose the counter  26 . The cover  36  is mounted onto the barrel  18  by means of a snap fit (not shown). Window  38  is positioned in sidewall  58 , allowing viewing of indicia  40  and  42 . Indicia  42  are positioned on a radially outwardly facing side surface  60  extending circumferentially around the tens wheel  34 . Alternatively, the indicia  42  can be positioned on the radially inwardly facing side surface extending circumferentially around the tens wheel  34 . Side surface  60  is positioned concentric with central axis  46  and is adjacent to sidewall  58 . Indicia  42  thereon are positioned so as to align with and be visible through the window  38  as the tens wheel rotates within the cover  36 . The tens wheel  34  is a decimal wheel showing tens of doses that can still be delivered before the device is considered empty, and thus, the indicia  42  thereon are positioned and spaced apart on the side surface  60  to align to the left side of the window  38 , leaving room in the window for indicia  40  on the unit wheel  30  to be displayed through window  38  to the right of the indicia  42  on the tens wheel  34  to properly indicate the unit number of doses that can still be delivered before the device is considered empty.  
         [0034]    A set of inwardly facing gear teeth  62  are positioned circumferentially around the tens wheel  34  above the flange  48 . Gear teeth  62  allow the tens wheel  34  to move only when driven by the device and thus prevents freewheeling of the tens wheel  34 . As best shown in FIG. 2, slave wheel  32  is mounted on an offset axle  66  extending upwardly from the bottom  44  of the cover  36 . Axle  66  is offset from the central axis  46  and thereby provides an offset axis of rotation  68  about which the slave wheel  32  rotates. As shown in FIG. 3, a gear  70  is positioned on one face  72  of the slave wheel  32 , the gear  70  meshing with the gear teeth  62  on the tens wheel  34  such that rotation of the slave wheel  32  about the offset axis  68  drives the tens wheel  34  in rotation about the central axis  46  (see also FIG. 8). As shown in FIG. 2, a geneva wheel  74  is positioned on the opposite face  76  of the slave wheel  32 . As shown in FIGS. 6 and 7, the geneva wheel  74  has a plurality of receptacles  78 , four being shown by way of example. The receptacles  78  are positioned in spaced relation circumferentially around the geneva wheel. Each receptacle is sized and positioned to receive a foot  80  extending downwardly from the unit wheel (see also FIG. 3). The foot  80  engages one of the receptacles  78  once on each complete revolution of the unit wheel  30 , and rotates the geneva wheel  74  about the offset axis  68 . When the geneva wheel  74  has four receptacles  78 , the geneva wheel rotates through an angle of about 90° about the offset axis  68 . As shown in FIG. 2, rotation of the geneva wheel  74  causes a corresponding rotation of the gear  70  (since both the geneva wheel  74  and the gear  70  are on opposite faces of the slave wheel  32 ) which drives the tens wheel  34  in rotation about central axis  46 . The geometry and positioning of the geneva wheel  74 , gear  70  and the indicia  42  on the tens wheel  34  are such that rotation of the slave wheel  32  positions the next indicia  42  visible within the window  38 .  
         [0035]    As shown in FIG. 2, unit wheel  30  is rotatably mounted on a central axle  82  substantially aligned with the central axis  46  and extending from the bottom  44  of the cover  36 . Unit wheel  30  comprises a radially outwardly facing side surface  84  extending circumferentially around and upon which the unit indicia  40  are positioned. Alternatively, the unit wheel may comprise a transparent radial side surface  84  extending circumferentially around, upon which the unit indicia may be positioned on the inward face of said surface so as to still be readable from the outwardly facing surface. As shown in FIGS. 4 and 4A, the unit wheel  30  is nested within the tens wheel  34  such that the outwardly facing side surfaces  60  and  84  are coaxial with and adjacent to one another. The side surface  60  on the tens wheel  34  is transparent, thus, allowing the indicia  40  on the unit wheel behind it to be visible, together with the indicia on the tens wheel  34 , through the window  38 . The unit indicia  40  are positioned and spaced around side surface  84  so as to align to the right side of the window  38 . Thus, together, the tens indicia  42  on the tens wheel  34  and the unit indicia  40  on the unit wheel  30  are visible together in the window  38  to show the number of doses that can still be delivered before the device is considered empty or doses already dispensed from the medicament reservoir  16 . Positioning the foot  80  on the unit wheel  30  and the gear teeth  62  on the tens wheel  34  is the preferred configuration, although other configurations, for example, having two or more feet on the unit wheel, altering the ratio of the size of the slave wheel to the master wheel and having a plurality of receptacles, are also feasible.  
         [0036]    As shown in FIGS. 2, 6 and  7 , slave wheel  32  has a plurality of lobes  86  positioned between the gear  70  and the geneva wheel  74 . The lobes  86  extend radially outwardly and are arranged in spaced relation circumferentially about the slave wheel  32 , each lobe  86  being positioned next to a corresponding receptacle  78  of the geneva wheel  74 . In the example shown, there are four lobes  86  positioned next to corresponding receptacles  78 . Lobes  86  engage an inwardly facing circumferential surface  88  on the unit wheel  30 . Engagement of two adjacent lobes  86  with the surface  88  prevents rotation of the slave wheel  32  as the unit wheel  30  rotates and hence also prevents rotation of the tens wheel  34 . However, there is a notch  90  positioned within the surface  88  adjacent to the foot  80 . When the foot  80  engages a receptacle  78  on the geneva wheel  74  as shown in FIG. 6, the lobe  86  adjacent to the receptacle  78  is received within the notch  90  in the circumferential surface  88  of the unit wheel  30 . The notch  90  provides clearance between the lobe  86  and the circumferential surface  88 , allowing the slave wheel  32  to rotate, thereby rotating the tens wheel  34 . After the foot  80  has disengaged from the receptacle  78  as depicted in FIG. 7 and is no longer rotating the slave wheel  32 , the next pair of adjacent lobes  86  then align with the circumferential surface  88 , thereby, again preventing rotation of the slave wheel until the foot  80  on the unit wheel  30  again engages the next receptacle  78  aligned with the next lobe  86  on the geneva wheel  74 .  
         [0037]    As shown in FIG. 2, the unit wheel  30  is driven by coupling  28  which couples the motion of the air channel assembly  14  to the counter  26 . Coupling  28  has a plurality of legs  94  which extend from the counter  26  into the barrel  18  and engage tabs  111  on the mandrel  24  (not shown) of the air channel assembly  14 . Legs  94  are arranged in spaced relation to one another so as to provide for lost motion between the mandrel  24  (not shown) and the coupling  28 . The lost motion allows for the large rotational motion of the air channel assembly  14  relative to the drive sub-assembly needed to actuate the inhaler, yet also provides a reduced rotational motion of the air channel assembly  14  relative to the counter  26  needed to actuate the counter. Legs  94  are flexible and, thus, may be resiliently bent to facilitate assembly of the counter onto the inhaler by allowing the legs to flex and be inserted into barrel  18 .  
         [0038]    Mounted on the coupling  28  opposite to the legs  94  is a ratchet  96  which engages pawls  98  on the unit wheel  30  (see also FIG. 5). Thus motion of the air channel assembly  14  relative to the barrel  18  as the inhaler is actuated is transmitted from the mandrel  24  (not shown) to the unit wheel  30  by means of the legs  94 , the ratchet  96  and the pawls  98  on the unit wheel  30 . The ratchet and pawl are used to move the unit wheel only in one direction to decrement (or increment) the counter for each actuation. As described in detail below, actuation of the inhaler  10  requires a reciprocal motion of the air channel assembly  14  relative to the barrel  18 , and the reciprocal motion must be converted to unidirectional motion of the counter  26 , and this is effected by means of the ratchet  96  and pawls  98 . The position of the ratchet  96  on the coupling  28  and pawls  98  on the unit wheel  30  are preferred for ease of manufacture but could easily be reversed and achieve the same desired effect. By keeping both sets of pawls  98  on the same part, variations between the arms in the inhaler device is negated, thus providing a more consistent torque balance.  
         [0039]    As shown in FIG. 3, a second ratchet  100  is positioned on the end of barrel  18 . As shown in FIG. 5, the ratchet  100  faces radially inwardly to engage pawls  102  which are mounted on the unit wheel  30  and face outwardly to engage the ratchet  100 . Ratchet  100  and pawls  102  work in cooperation with ratchet  96  and pawls  98  to prevent retrograde motion of the unit wheel when it is actuated by the reciprocal motion of the air channel assembly  14  relative to the barrel  18 . The cooperation of the ratchets and pawls is described in detail below in the description of counter operation. Uni-directional motion of the unit wheel is ensured by proper design of the ratchet angles and relative panel lengths of the ratchets  96  and  100  and pawls  98 .  
         [0040]    As illustrated in FIG. 3, unit wheel  30  also has a plurality of cantilevered fingers  104  which extend upwardly from the unit wheel and engage the coupling  28 . The fingers  104  act as springs to bias the components of the counter  26  against the bottom  44  of cover  36  and the fingers  104  also bias the coupling  28  against the mandrel  24  (not shown). When compressed against the coupling  28 , the unit wheel  30  is biased against the tens wheel  34 , keeping the slave wheel  32  properly positioned and engaged with the unit and tens wheels. The biasing action of the fingers  104  also keeps the tens wheel  34  properly seated on the bottom  44  and the flange  48  firmly engaged with the raised boss  50  so as to generally ensure smooth operation of the counter and also help prevent powdered medicament from contaminating the counter mechanism.  
         [0041]    It is preferred to make the inhaler and counter from plastic materials for cost effective manufacture by injection molding. For example, the barrel  18 , cover  26 , and cap  12  may be polypropylene, the tens wheel  34  may be polycarbonate, the slave wheel  32  may be polybutylene teraphthalate, while the unit wheel is preferably polycarbonate, the coupling may be polybutylene terephthalate, and the air channel assembly is predominantly made of an acetal copolymer such as Hostaform®.  
         [0042]    The term “medicament” as used herein is intended to encompass the presently available pharmaceutically active drugs used therapeutically and further encompasses future developed therapeutically effective drugs that can be administered by the intrapulmonary route. Drugs may be selected from, for example, analgesics, e.g. codeine, dihydromorphine, ergotamine, fentanyl or morphine, anginal preparations, e.g. diltiazem; antiallergics, e.g. cromoglycate, ketotifen or nedocromil; antiinfectives e.g. cephalosporins, penicillins, streptomycin, sulphonamides, tetracyclines pentamidine, and Neuraminidase Inhibitors; antihistamines, e.g. mnethapyfilene; antitussives, e.g. noscapine; beta-adrenergics that include bronchodilators such as ephedrine, adrenaline, fenoterol, forinoterol, isoprenaline, phenylephrine, phenylpropanolamine, reproterol, rimiterol, isoetharine, tulobuterol, orciprenaline, or (−)4-amino-3,5-dichloro-.alpha.-[[[6-[2-(2-pyridinyl)ethoxy]hexyl]-amino]methyl]benzenemethanol, epinephrine (Primatene), formoterol (Foradil), isoproterenol (Isuprel), isoetharine (Bronkosol), metaproterenol (Alupent, Metaprel), albuterol (Proventil, Ventolin), terbutaline (Bricanyl, Brethine), bitolterol (Tornalate), pirbuterol (Maxair), salmeterol (Serevent), salmeterol+fluticasone combination (Advair Diskus), and albuterol+atrovent combination (Combivent); sodium channel blockers such as amiloride, anticholinergics e.g. ipratropium, atropine or oxftropium; hormones, e.g. cortisone, hydrocordisone or prednisolone; and therapeutic proteins and peptides, e.g. insulin or glucagon; anti-inflammatory drugs used in connection with the treatment of respiratory diseases include steroids such as ciclesonide beclomethasone dipropionate (Vanceril, Beclovent), budesonide (Pulmicort), dexamethasone, flunisolide (Aerobid), fluticasone (Flovent), salmeterol+fluticasone combination (Advair Diskus), and triamcinolone acetonide (Azmacort), and Mediator-release inhibitors such as cromolyn sodium (Intal), and nedocromil sodium (Tilade); leukotrine (LT) inhibitors, vasoactive intestinal peptide (VIP), tachykinin antagonists, bradykinin antagonists, endothelin antagonists, heparin furosemide, anti-adhesion molecules, cytokine modulators, biologically active endonucleases, recombinant human (rh) DNase compounds, alpha-antitrypsin and disodium cromoglycate (DSCG); and lung surfactants such as lipid-containing compositions as described in TONGE et. Al, WO 99/09955; Pulmonary surfactants as decribed in Devendra et. Al, Respir Res 2002, 3:19; Infasurf®available from ONY; Curosurf®available from Dey Laboratories; Exosurf® by Glaxo Wellcome; Survanta available from Abbot; and Surfaxin® lung surfactant available from Discovery Laboratories.  
         [0043]    The term “intermittent drive transfer mechanism” as used herein means a mechanism that intermittently transfers the drive from one element to another via a drive transfer wheel. An example of such a mechanism is a geneva mechanism.  
         [0044]    The term “drive transfer wheel” as used herein means a wheel capable of intermittently transferring a drive from one element to another. Examples of a drive transfer wheel include a geneva wheel, a star drive wheel or a maltese cross wheel. Preferably, the drive transfer wheel is a geneva wheel.  
         [0045]    Inhaler and Counter Operation  
         [0046]    Operation of the inhaler  10  is described in detail in Drought N., U.S. Pat. No. 5,678,538, which is hereby incorporated by reference in its entirety. Provided below is a simplified explanation of inhaler operation as it relates to the counter  26 .  
         [0047]    With reference to FIGS. 1 and 2, to administer a metered dose of powdered medicament, a user grasps the barrel  18  in one hand and the dust cap  12  in the other. The cap  12  and barrel  18  are rotated relatively to one another through an angle of about 105° about the central axis  46  with the cap  12  rotating clockwise and the barrel  18  counterclockwise when viewed from the cap end of the inhaler  10 . Cap  12  has a tab  106  which engages a notch  108  in collar  22 , causing the entire air channel assembly  14  to rotate clockwise along with the cap  12 . The cap  12  and barrel  18  are then relatively rotated in the reverse direction through the same angle. The reciprocal rotation of the cap  12  and air channel assembly  14  causes a metered dose of powdered medicament to be scraped from the reservoir  16  and deposited in the air channel assembly  14 . The user removes the cap  12 , places his or her lips to the mouthpiece  20  and inhales. The medicament becomes entrained in an air stream drawn through the mouthpiece  20  and is drawn into the mouth, trachea and lungs of the user where it is absorbed.  
         [0048]    The relative rotation between the barrel  18  and the air channel assembly  14  is used to actuate the counter  26 . By way of example only, a decrementing counter, which counts down and indicates the number of doses that can still be delivered before the device is considered empty, is described below, it being understood that an incrementing counter, which counts upward and indicates the number of doses administered, functions in essentially the same way as the decrementing counter. Changing a decrementing counter to an incrementing counter is easily carried out by changing the arrangement of the printed numbers on the tens and unit wheels. References to clockwise and counterclockwise rotations which follow are defined as if viewed from the dust cap  12  of the inhaler along central axis  46 .  
         [0049]    The initial clockwise rotation of the air channel assembly  14  through about 105° is transmitted to the unit wheel  30  by the coupling  28 . Legs  94  engage the mandrel  24  (not shown) on the air channel assembly to transmit the motion. There is lost motion between the legs  94  and the mandrel  24  over an angle of about 56.5°. After this point in the rotation, the mandrel contacts the legs and rotates the coupling  28  through an angle of about 48.5° clockwise. As shown in FIG. 5, ratchet  96  on the coupling is rotated clockwise relatively to pawls  98  on the unit wheel, the pawls  98  slipping over the ratchet teeth  96   a  and clicking into place on the other side of the teeth, ready to move the unit wheel  30  upon the reverse rotation of the air channel assembly  14 . The unit wheel  30  is prevented from rotating clockwise as the pawls  98  engage and slip over the teeth  96   a  by the second ratchet  100  located in barrel  18 , engaged by outer pawls  102  on the unit wheel  30 . Note that the pawls  98  are stressed in bending only during motion of the coupling  28  relative to the unit wheel. At all other times, the pawls remain unstressed and, thus, will not take on a permanent set which could adversely affect the ratcheting action of the mechanism.  
         [0050]    The user then turns the cap  12  relative to the barrel  18  through a counterclockwise rotation of about 105°, loading a dose of medicament into the air channel assembly  14  and also causing the counter to decrement one unit. Again, there is lost motion between the mandrel  24  and the coupling  28  over about 56.5° of the rotation. After this point, the mandrel  24  causes the coupling  28  to rotate counterclockwise through an angle of about 48.5°. During this rotation, ratchet  96  (see FIG. 5), rotating counterclockwise, engages pawls  98  on the unit wheel  30  and rotates the unit wheel counterclockwise about the central axis  46  so that the next lower value of the indicia  40  is displayed in the window  38 . There is lost motion between the ratchet  96  and pawls  98  such that the unit wheel  30  is rotated though an angle of 36°, thus, providing ten decrements of the unit wheel over a complete revolution through 360°. The lost motion is obtained by appropriate spacing of the ratchet teeth  96   a . Upon counter clockwise rotation of the unit wheel  30 , the pawls  102  slip over the ratchet teeth  100   a  to engage the next teeth and lock the unit wheel in place until the next dose is loaded by the clockwise and counterclockwise rotation of the air channel assembly  14  relative to the barrel  18 .  
         [0051]    On each tenth decrement of the unit wheel  30 , the foot  80  extending therefrom engages one of the receptacles  78  on the geneva wheel  74  as shown in FIG. 6. Counterclockwise motion of the unit wheel  30  through the tenth decrement causes counterclockwise rotation of the slave wheel  32  about the offset axis  68 . Rotation of the slave wheel  32  is permitted because the lobe  86  adjacent to the receptacle  78 , which normally engages the surface  88  of the unit wheel to prevent rotation, is received within the notch  90  in the surface  88 , providing clearance allowing the slave wheel to rotate. Over the 36° of rotation of the unit wheel  30 , the first and last 3° are lost motion relative to the slave wheel  32 , and the middle 30° rotates the slave wheel through 90°. The purpose of the lost motion is to ensure that immediately before and after the tens stroke, the foot is not engaged with the receptacle, which means that the geneva mechanism cannot be driven by the user driving the tens wheel. As shown in FIG. 8, gear  70  on the slave wheel  32  also rotates counterclockwise through 90°, its teeth engaging the gear teeth  62  on the tens wheel  34 , and causing a counterclockwise rotation of the tens wheel  34  about the central axis  46  to bring the next lower indicia  42 , indicating tens of doses, into view within the window  38 . Indicia  40  on the unit wheel  30  are visible through the transparent tens wheel  34  and align with the indicia  42  on the tens wheel and together indicate the number of doses that can still be delivered before the device is considered empty. The gear ratio between gear  70  and the tens wheel  34  is designed to move the tens wheel in proportion to the number of divisions, indicated by the indicia  42 , on the tens wheel  34 . For example, a dose counter having 120 doses will require  13  divisions, corresponding to indicia from 1-12 and a blank space indicating zero, positioned on the tens wheel  34 . Thus, with each complete revolution of the unit wheel (with ten divisions numbered 0-9), the tens wheel  34  should move through an angle of about 27.7° ({fraction (1/13)} of a complete revolution). Note that this rotation must be achieved by a 90° rotation of the gear  70 . A ratio of about 3.25 to 1 between the tens wheel  34  and the gear  70  will cause the desired rotation of the tens wheel  34 . As best shown in FIG. 3, it is advantageous to provide colored indicators  110  on the tens wheel  34  positioned near the low numbered indicia  42  to provide a readily visible warning that few doses remain in the inhaler.  
         [0052]    A complete revolution of the tens wheel  34  is prevented by the engagement of tab  54  with the stop block  56  positioned within the circular groove  52  in the bottom  44  of cover  36  (see FIGS. 2 and 8). As shown in FIG. 8, tab  54  is initially positioned adjacent to one side  56   a  of the stop block  56  (the position corresponding to the maximum indicia  42  being aligned within window  38 ) and initially moves counterclockwise away from the stop block as the tens wheel  34  rotates. When fewer than ten doses remain within the inhaler, the space on the tens wheel  34  aligned within window  38  is blank, displaying one of the colored indicators  110 , and the tab  54  is engaged with the opposite side  56   b  of the stop block  56 . This prevents any additional rotation of the tens wheel  34  after the final ten decrements of the unit wheel, thus, preventing the counter  26  from resetting itself by aligning the maximum tens indicia  42  within the window, which would occur if the tens wheel  34  were permitted to revolve beyond the complete revolution. However, even though the counter indicates no doses remaining, there may still be sufficient medicament in the reservoir to provide additional therapeutic doses to the user. The inhaler is designed so that the counter  26  may be overridden to administer any additional doses remaining after zero doses are indicated. Override of the counter is possible due to the design of ratchet  96  and pawls  98 . When the tens wheel  34  is prevented from turning, and upon application of sufficient torque by the user turning the cap  12 , the pawls  98  will slip over the ratchet teeth  96   a  as the coupling  28  moves in the counterclockwise direction, thereby allowing a medicament dose to be loaded into the air channel assembly without actuating the counter  26 . Normally, the pawls  98  engage the teeth  96   a  of ratchet  96  when the ratchet turns in the counterclockwise direction to actuate the counter  26 . However, the pawls  98  are sufficiently flexible such that they will disengage from the ratchet rather than jam the entire inhaler mechanism when sufficient torque is applied and the tens wheel  34  is blocked by the stop block  56 .  
         [0053]    The inhaler and counter according to the invention provides a compact, inexpensive and reliable means for administering measured doses of a powdered medicament, while knowing with a significant degree of precision how many doses are remaining in the inhaler at any given time and when an inhaler should be replaced with a new one.  
         [0054]    One skilled in the art will readily appreciate that the present invention is well adapted to carry out the objects of the invention, and obtain the ends and advantages mentioned, as well as those inherent therein. The inhaler, counter, slave wheel, methods, and articles of manufacture described herein are presented as representative of the preferred embodiments, or intended to be exemplary and not intended as limitations on the scope of the present invention.