Abstract:
A method of producing a container ( 201, 231, 350 ) having a plurality of apertures (eg  202, 232, 352 ) each containing a respective dose of powdered material, such as a medicament, involves placing an empty container in a position in which its apertures communicate with a reservoir ( 216, 84 ) of powdered material. The material is then passed, for example by the flow of gas, from the reservoir into the apertures to fill the latter, and the container is then separated from the reservoir and the apertures are optionally sealed with sheet material ( 204, 206, 321, 323 ). Since the apertures are filled, their volume determines the amount of each dose which therefore does not have to be measured prior to introduction into the apertures. The container may comprise a rigid or flexible plate and in latter case can be subsequently rolled into the form of a cylinder for use in an inhaler. Apparatus for performing the method, and an inhaler for use with a cylindrical container, are also shown.

Description:
FIELD OF THE INVENTION 
     The invention relates to a method of providing a container and a plurality of individual doses of particulate material, particularly powdered medicament, contained therein, and to apparatus for performing the method. The invention is of particular application to devices for administering single doses of powdered medicament by inhalation. 
     BACKGROUND TO THE INVENTION 
     It is known to provide a pharmacologically active compound in finely divided particulate form for self administration by inhalation to relieve respiratory problems, particularly asthma. 
     Such compounds can be provided in containers, each of which has a number of compartments, each containing a respective dose of the compound. Such containers are used in conjunction with an inhaler which releases each dose of the compound in turn. For example, European Patent specification No EPO 211595 (Glaxo Group Limited) shows an inhaler in which particular material is administered from a disc-shaped blister pack. 
     The blisters of the disc are loaded with powder by means of a filling head which separates individual doses of compound from a reservoir and allows those doses to pour into the blisters. The inherent inaccuracies in the measurement of each dose, and the need to provide a powder with suitable flow characteristics to enable filling result in the compound having to be mixed with a significant amount of lactose. 
     This increases the required size of the individual blisters in the container, thus reducing the number of doses which can be dispensed from a container of a given size. In addition, the user, in self administering a dose of medicament, has to inhale a relatively large amount of powder which can give rise to an unpleasant sensation in the user&#39;s mouth and throat. 
     SUMMARY OF THE INVENTION 
     According to a first aspect of the invention, there is provided a method of loading a container having a plurality of compartments, with a plurality of doses of a predetermined amount of particulate material, the method comprising the steps of: 
     1. bringing each compartment into a position in which it communicates with a reservoir of an excess amount of the particulate material; 
     2. causing the material to enter and fill the compartments; and 
     3. separating the compartments from the reservoir, wherein each compartment contains a respective dose and the volume of each compartment determines the amount of dose contained therein. 
     Preferably, the particulate material is a powdered medicament which may to advantage be of a type which is self administered by inhalation using an inhaler. 
     Since each dose of material is effectively metered by the compartments in the container, the need for measuring the doses before filling the container is avoided, the amount of material in each compartment is more accurately controlled, and the need for any substantial amount of additional material, such as lactose, is reduced or avoided. Consequently, the container can be configured to hold a relatively large number of doses, and the user does not have to inhale a large amount of particulate material when self administering one such dose. 
     Preferably, the container comprises a plate and each compartment comprises a respective aperture therein. 
     Preferably, the compartments are all simultaneously brought into a position in which they communicate with a common reservoir. 
     Preferably the particulate material is drawn into the apertures by passing a gas through the particulate material in the reservoir and the apertures. 
     The use of gas provides additional control over the force with which the particulate material is urged into the apertures, and hence the density of the material therein. 
     Preferably, before the particulate material is applied, the plate is placed on a porous bed beneath the reservoir, which bed allows the passage of said gas therethrough, whilst preventing particulate material from passing all the way through the apertures and escaping from the underside of the plate. 
     Preferably, the bed comprises a perforated base plate and a sheet of finely porous material, for example filter paper, interposed, in use, between the base plate and the container. 
     The apertures, once filled, are preferably sealed so that each dose is individually encapsulated in its respective aperture, and said sealing is conveniently achieved by bonding a respective sheet of material to each face of the plate. 
     Preferably, the sheet material which seals the apertures comprises a laminated foil which is attached to the body by being heat sealed thereto. 
     The laminated foil tends to resist any tendency for fragments of the sheet to be broken off the rest of the sheet when the seal for a given compartment is ruptured to allow material to be discharged from that compartment. 
     The plate may be flexible, in which case the method preferably includes the steps of rolling or otherwise forming the plate into a cylinder once it has been filled. 
     The container may be retained in its cylindrical configuration by applying an annular end cap thereto, typically two said end caps are used one at each end. 
     Such a plate preferably comprises an array of elongated flat, substantially rigid strips, adjacent pairs of which are hingeable relative to each other, such that the strips are substantially parallel to the axis of the cylinder in the finished container. 
     Alternatively, the plate can constitute one of a number of strips which are fitted together to form a cylindrical composite container. 
     Preferably, the reservoir is contained in a hopper having an array of outlet holes, each of which is in registry with a respective aperture when the apertures are in said position relative to the reservoir, and said gas is supplied to the hopper under sufficient pressure for the particulate material to pass through the outlet holes and into the apertures. 
     Preferably, the dimensions of the outlet holes are such that substantially none of the particulate material passes therethrough when gas is not being supplied to the hopper. 
     Thus, by interrupting the supply of gas to the hopper, it is possible to remove the plate therefrom without any substantial amount of particulate material being lost from the bottom of the hopper. 
     According to a second aspect of the invention, apparatus for performing the method of the first aspect of the invention comprises a porous bed on which the plate can be laid out flat; a filling head for supplying particulate material to the upper surface of the plate and means for moving air or a gas through the bed and the apertures in the plate to draw particulate material thereinto. 
     Preferably, the filling head comprises a hopper having a series of outlet holes, the relative positions of which correspond to those of the aperture in the plate so that, with the plate in position under the hopper, each hole is in registry with a respective aperture. 
     Preferably, the apparatus includes level detection means for determining the level of particulate material remaining in the hopper, and supply means for supplying further particulate material thereto. 
     If the hopper is elongate, the supply means and level detection means are preferably so arranged that material is supplied to one end of the hopper, and the level detection means detects the level of the material at the opposite end of the hopper, the apparatus including distribution means for levelling the particulate material in the hopper. 
     The invention also lies in a method of making a cylindrical body having a plurality of compartments, each containing a respective dose of material, the method comprising the steps of: 
     (1) applying particulate material to one face of each of a plurality of elongate substantially flat members, each said member having a plurality of compartments accessible from said face; 
     (2) causing the particulate material to enter said compartments; 
     (3) joining the members together to form a composite member consisting of said elongate members positioned side by side; and 
     (4) rolling, or otherwise forming, the composite member into a generally cylindrical form in which each said elongate member extends along the length of the body. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     The invention will now be described, by way of example only, with reference to the accompanying drawings in which: 
     FIGS. 1A-1H are simplified diagrams showing various stages of a method, in accordance with the invention, of making a cylindrical container; 
     FIGS. 2A-2E show components of an alternative type of cylindrical container which can be filled by the method illustrated in FIGS. 1A-H, FIG. 2E showing the container when assembled; 
     FIG. 3 is a plan view of the apparatus for performing a modified version of the method, the apparatus having a number of stations, arranged around the carousel, at which various steps are performed; 
     FIG. 4 is a diagrammatic sectional view taken in a radial plane, of the first of said stations; 
     FIG. 5 is a diagrammatic sectional view, taken in a radial plane, illustrating a second of said stations and the steps carried out thereat; 
     FIG. 6 is a similar view of elements which are transported along the carousel from the second to the third station; 
     FIGS. 7-11 are radial sectional views of the third station at various stages of its operation; 
     FIGS. 12-16 are radial sections of parts of the fourth station at various stages in its operation; 
     FIGS. 17 and 18 are similar views of the fifth of said stations; 
     FIG. 19 is a similar view of the sixth station 
     FIG. 20 shows parts of the seventh station; 
     FIG. 21 shows the elements which are transported from the seventh station to the eighth station; 
     FIG. 22 is a partially cut away isometric view of an inhaler for dispensing doses of powdered medicament from the finished container, which forms part of a cartridge housed in the inhaler; 
     FIGS. 23-26 are exploded isometric views of various components of the cartridge; 
     FIG. 27 shows the cartridge when assembled; 
     FIG. 28 is a diagrammatic partially exploded view of the cartridge and the housing; 
     FIGS. 29A-29F are diagrammatic sectional views illustrating the operation of part of the inhaler, at various stages during its cycle of operation; 
     FIGS. 30A-30F are sectional views illustrating the operation of other parts of the device at corresponding stages in the operating cycle thereof; and 
     FIG. 31 is a side view of a component of the inhaler; 
     FIG. 32 is an end view of that component; 
     FIG. 33 shows from the front an alternative type of container which can also be filled by a method in accordance with the invention; 
     FIG. 34 shows a detail of that container; and 
     FIG. 35 is a side view of that container. 
    
    
     DETAILED DESCRIPTION 
     With reference to FIGS. 1A-1H, a container comprises a body  201  which includes a number of through-bores, eg  2 , for containing a respective dose of medicament. For the sake of clarity, the body illustrated in FIGS. 1A-1H has only 16 such through bores, although in practice a larger number of through bores may be present in the body  201 . 
     In the finished container, the body  201  is of a generally cylindrical shape, and the bores are radially disposed, and are sealed by an outer sheet  204  and an inner sheet  206  of laminated foil heat sealed to the body  201 . 
     With reference to FIG. 1A, the body  201  comprises a rectangular plate of a plastics material, the underside of which includes a number of grooves  208  arranged in a regular parallel array. The grooves  208  divide the member into a number of parallel rigid strips, such as strip  210  running across the width of the plate. Adjacent pairs of strips are connected by corresponding reduced thickness-portions, such as portion  12 . The thickness of the plastics material constituting those portions is such that the adjacent strips are hingeable relative to each other. The through bores in the body  201  are all provided in the strips. 
     The plate  201  is laid flat on a bed  214  of a porous material, with the non grooved face of the body upper most, and the upper surface of the plate  201  is covered with a layer of powdered medicament  216 , which covers one end of each of the through bores. 
     With reference to FIG. 1C, nitrogen is then passed down through the layer  216  of the through bores through the bed  214 , causing the material  216  to pass into each of the through bores. The porosity of the bed  214  is such that it is impervious to the material  216 . As a result, the bed  214  prevents material  216  being discharged from the bottom of the through bores. 
     When the through bores have been filled with the material  216 , any excess material which has not been drawn into a through bore is removed by drawing a resiliently flexible blade  218  across the upper surface of the plate  201  (FIG.  1 D). The sheet  204  is then heat sealed onto the upper surface of the plate  1  (FIG.  1 E), which is then inverted so that the sheet  206  can be similarly applied to the opposite face of the plate  1  (FIG.  1 F). 
     The flexibility provided by the reduced thickness portions between the strips of the plate  201  enable the latter to be rolled (FIG. 1G) into a generally cylindrical shape, with the strips extending axially along the cylinder, and the grooves  208  on the inner surface thereof. 
     Two ring-shaped end caps  220  and  222  are then attached one at each end of the cylinder. Each cap includes an annular track, eg track  224 , into which the strips extend and in which the strips are a tight fit. Thus the caps  220  and  222  prevent the cylinder from unravelling. The components shown in FIGS. 2A-2E correspond with those shown in FIGS. 1A-H, and corresponding components are indicated by the same reference number raised by  30 . Thus the container comprises a body  231  which is formed by rolling a plate (also referenced  231 ), and which has a number of through-bores eg  232  which are filled with powdered medicament by means of the same method as illustrated in FIG. 1, and are sealed on one side by a first sheet of laminated foil  234  and on the other side by a second sheet of laminated foil  236  applied to the plate  231  after it has been inverted. 
     It will be seen that the body  231  contains a larger number of through-bores, eg  232 , than the body  1 , and can therefore contain a greater number of doses of medicament than the body  201 . In addition each of the grooves in the plate  231 , eg groove  238 , is tapered so as to facilitate rolling. The caps  250  and  252  each include diametrically opposed inner slot arrangements, for example  256  and  258  which enable the container to be rotationally keyed to the rotational core or an inhaler in which the container is to be used. 
     As can be seen from FIG. 2A, the through-bores are so arranged as to lie on a helical path on the body  31 , when the container is assembled. 
     The apparatus shown in FIG. 3 comprises a carousel  1  and eight stations  2 - 9  positioned around the periphery thereof. In use, the carousel rotates in an anti-clockwise direction to transport components on the carousel to each of the stations in turn, as described below. 
     With reference to FIG. 4, the apparatus includes a holder  10  for releasably retaining a container in the form of a rectangular plate. The holder  10  has a first rectangular frame portion  12  having an inner peripheral rectangular flange  14  which bounds a rectangular central opening  16 . That gap accommodates a perforated metal block  18 . The holder  10  also includes a second rectangular frame  20  which is pivotally mounted on the frame  12 , and which also has a peripheral flange  22  and a central aperture  24 . The holder  10  is releasably attached to the carousel  1  through an apertured plate  26 . 
     As can be seen from FIG. 4, the station  2  includes a block  28  which has a central passage  30  which communicates with two feet  32  and  34 . The passage  30  is selectably connected to a source of vacuum, and the block  28  is mounted on a pneumatic piston and cylinder assembly  38  which is operable to raise and lower the block  28 . The piston and cylinder assembly  38  is, in turn, suspended from an upper plate  40  (FIG. 3) through drive means (not shown) operable to move the assembly  38 , and hence the block  28 , radially. 
     A reel  42  of filter paper is provided at the radial outer end of the station  2 , which includes a punch and die mechanism (not shown) for cutting the filter paper to length. 
     The block  28 , in use, retrieves a cut-out for filter paper from the radial outer end of the station  2 , a vacuum being applied to the passage  30  to retain the cut-out on the feet  32  and  34 , conveys it radially inwards to the position shown in FIG. 4, and then lowers the filter paper onto the block  18 . The vacuum is then disconnected so that when the block is raised, the filter paper remains in the holder  10 . 
     The holder  10  is then conveyed on the carousel  1  to the station  3 , which is shown in more detail in FIG.  5 . The station  3  has a pneumatic gripper  44  which is mounted on an upper plate  46  through a pneumatic piston and cylinder assembly  48 , which, in turn, can be radially moved by drive means (not shown). In use, the gripper  44  collects a container  50  from a magazine  52  at the radial outer end of the station  3 , conveys the container  50  to the position shown in FIG.  5  and places it in the holder  10  on the filter paper (referenced  54 ). The gripper  44  is then removed and the frame  20  is lowered onto the frame  12  so that the filter paper  54  and container  50  are clamped between the flanges  14  and  22 . The container  50  comprises a flexible plate having an array of apertures, one of which is referenced  56 . The container is similar to the containers shown in FIGS. 1A and 2A. 
     The holder, with the container and filter paper retained therein (as shown in FIG.  6 ), is then transported to the filling station  4  which is shown in FIG.  7 . In FIGS. 6 to  21 , the holder  10  is shown in a simplified form, for the sake of clarity. 
     The filling station  4  comprises a filling head  59  having a rectangular inlet manifold  58  which communicates with a pipe  60  through which pressurised nitrogen can be selectively supplied to the manifold. The manifold  58  is sealed against a rectangular upper frame portion  62  by an o-ring seal  64 . The portion  62  includes a central rectangular opening which accommodates a diffuser  64  in the form of a perforated block, a peripheral rectangular frame portion  66  surrounds the portion  62 , and defines, with the portion  62 , a first end aperture which accommodates an inlet chute  68 , along which powdered medicament is supplied, in use, from an auger  70  via valve  72 . The frames  62  and  66  also define an aperture opposite said chute  68  for accommodating an ultrasonic level sensor  74 . The peripheral frame includes a further aperture in one side thereof through which a rod  76  extends. The end of the rod is attached to a rectangular plate  79 , the elongate axis of which extends substantially perpendicular to the plane of FIG.  7 . 
     A hopper  78  is sealed against the base of the frame  66  to an o-ring seal  80 . The bottom of the hopper  78  includes a linear array of holes, one of which is denoted  82  which are in positions corresponding to the positions of the apertures in the container  50 . The assembly positioned above the holder  10  in container  50  can be lowered into the position shown in FIG. 9, in which the bottom of the hopper  78  closely abuts the contained  50 , and the holes in the hopper  78  register with the apertures in the container  50 . 
     Powdered medicament  84  is then introduced into the hopper through the chute  68 . The detector  74  then senses the level of the medicament  84  at the end of the hopper opposite the chute  68 , and if that level is insufficient, the rod  76  is extended, causing the plate  79  to redistribute the medicament  84  over the holes in the hopper. 
     Nitrogen is then introduced through the pipe  60 , and passes through the diffuser  64  (which prevents the flow of nitrogen adversely affecting the distribution of the particulate material  84 ) through the material  84 , the holes in the bottom of the hopper  78  and through the apertures in the container  50 . Nitrogen exiting the apertures in the container  50  passes through the block  18  via the filter paper  54 . This passage of nitrogen urges the powdered medicament  84  through the holes in the hopper  78  and into the apertures in the container  50 , whilst the filter paper  54  prevents the powdered medicament being expelled through the bottom of the apertures. 
     The filling head  59  is then raised from the container  50  as shown in FIG. 12, and a further charge of powdered medicament is poured into the hopper for the next filling, and if necessary levelled by the plate  79 . The filled container  50  and its holder  10  are then transported by the carousel  1  to the station  5  which includes, at its radial outer end, a reel  300  of a web  302  of foil laminate, and feed-means (not shown) for feeding foil from the reel past a punch  302  and a die  304 , which die defines a rectangular aperture. A sealing head  306  is mounted at the same end of the station  5 , in registry with the aperture defined by the die  304  by means of a pneumatic piston and cylinder assembly (not shown) which is operable to raise and lower the head  306 . 
     The head  306  includes a heater  308  and a number of feet, one of which is referenced  310 , arranged in a rectangular array at the underside of the head  306 . Each foot is in the form of a short hollow cylinder, the interior of which communicates with a vertical passage, for example  312 . The vertical passages, in turn, communicate with a horizontal common passage  314  which is selectively connectable to a vacuum source (not shown). 
     With reference to FIG. 13, the punch  302  is al so mounted on a pneumatic piston cylinder arrangement (not shown) which is operable to raise the punch  302 , causing it to cut from the length of foil  301  a rectangular piece  313  which is moved up into contact with the head  306 . As this happens, the passage  314  is connected to the vacuum source which causes the feet on the head  306  to hold the piece  313  thereon. 
     The web of foil  301  is wider than the cut-out  313 , and as a result, when the punch  302  is returned to the position shown in FIG. 13, a fresh piece of foil can be drawn into position above the punch  302  by means of a reel assembly (not shown) positioned to the right of the components shown in FIG. 12, which is on the opposite side of those components from the reel  300 . 
     The piston and cylinder assembly on which the head  306  is mounted is mounted on a top plate  316  (FIG. 3) via a drive mechanism for moving the head  306  in either radial direction. Thus, once the cut-out  313  has been attached to the head  306 , the latter is raised into the position shown in FIG.  15  and the drive means operates to move the head radially inwards into the position shown in FIG. 16, in which it is positioned above the container  50 . 
     The head  306  is then lowered onto the container  50  as shown in FIG.  16 . The foil laminate of the cut-out  313  has an upper layer (in contact with the feet on the head  306 ) which is substantially unaffected by the heat from the heater. However, the lowermost layer of the laminate is partially fused by the heat from the heater  308 , causing the cut-out  313  to be heat-sealed to the container  50 . The passage  314  is then disconnected from the vacuum supply, and the head  306  is raised and returned to the position shown in FIG. 12, leaving the contained  50  with a foil laminate seal on one face. 
     With reference to FIG. 17, the container  50  and its holder  10  are then transported to the station  6  at which the container  50 , the support  10  and the plate  18  are removed from the carousel  1  and placed on a support block  320 . A similar support block  322  and perforated plate  324  are then placed on top of the container  50  and holder  10 . The supports  320  and  322  are connected to a mechanism (not shown) which inverts the elements shown in FIG. 17 in the way indicated by the arrows  326  in FIG. 18 so that the block  320  is then uppermost. The components shown in FIG. 18 are then transported to the station  7  which includes a head (not shown) which releasably grips the top of the support  320  and which has a suction mechanism which seals against the plate  324 , to cause the filter paper  54  to be held against the plate  18 . The head is then moved away from the container  50 , taking the block  320 , the plate  18  and the paper  54  with it, as shown in FIG.  19 . 
     The remaining elements shown in FIG. 19 are then transported to the station  8  which is similar in form and function to the station  5 , and which thus includes a reel  326  of foil laminate which is fed to a punch and die assembly similar to the punch and die  304  and  302 . The punch and die cut out a piece of the foil laminate which is then applied to a head  328  of the same kind as the head  306 . The head  328  is mounted at the station  7  by a similar arrangement used to mount the head  306  on the station  5 , so that the head  328  can move radially into the position shown in FIG. 20 in which is is directly above the container  50 . The head is then lowered, sealing the cut out piece of foil laminate to the container  50 . 
     FIG. 21 shows the container  50  in its filled and sealed form, still in its holder  10 . The sheets of foil laminate are referenced  321  and  323 . In this form, the container  50  an d holder  10  are fed to the station  9  at which the container  50  is removed from the holder  10  and rolled into the form of a cylinder in a similar fashion to the method previously described. 
     With reference to FIG. 22, an inhaler in which the container  50  can be used comprises a housing  100  which has a generally cylindrical portion and which is connected at its lower end to a mouth piece  102  extending substantially radially to the main body of the housing  100 . The opposite end of the housing  100  includes a rotary member in the form of a cap  104  rotably mounted on the rest of the housing  100 . The cap  104  incorporates a window  106  through which a cartridge  108  contained within the body  100  can be viewed. 
     With reference to FIGS. 23 to  26 , the cartridge  108  comprises a hollow cylindrical core  110  which has a reduced diameter upper portion  112  in which there is provided an upper aperture  114  and an integral tang  116 . The core  110  also includes a lower portion  118  which is of a larger diameter than the portion  112 , and which defines an annular shoulder  120  where it meets the portion  112 . The portion  118  includes an external screw thread  122 , a radial aperture  124  in its upper region, and two axially extending lower lugs  126  and  128 . 
     The core  110  accommodates a vertical shaft  130 , the upper part of which protrudes through the aperture  114 . The top of the shaft  130  includes a slot  132  for engaging a protuberance  136  on the underside of the top of the cap  104  so as to provide a rotational key between the shaft  130  and the cap  104 . The bottom of the shaft  130  is provided with a radial crank arm  138  which incorporates a radial slot  140  which slidably engages a boss  142  connected to a pin  144  positioned above a plate  146 . The pin is in registry with an aperture (not shown) in the case  110  angularly spaced from the aperture  124 . 
     The plate  146  is, with the cartridge assembled, attached to the interior of the core by suitable means (not shown), and the pin  144  and plate  146  include guide means (not shown) so arranged that rotation of the shaft  132  causes axial motion of the pin  144 . With reference to FIG. 25, the shoulder  120  supports a sleeve  150  which is rotably mounted on the core  110  and which surrounds the upper part  112 . 
     The sleeve  150  includes internal longitudinal serrations  152  and two diametrically opposed sets of external longitudinal ribs  154  and  156 . 
     With reference to FIG. 25, the medicament to be dispensed is contained in a cylindrical container  158  which has side walls which include a number of helically arranged radial through bores such as  159  (FIGS.  5  and  13 ), each of which contains a respective dose of material. The internal and external surfaces of the side walls are coated with corresponding sheets of a laminated foil which seals both ends of each bore. The container  158  is made by any one of the methods previously described. 
     The core  110  extends through the centre of the container  158  which includes a lower end cap  160  having a part helical groove (not shown) for engaging the thread  122 , and an upper cap  162  which includes two diametrically opposed sets of slots  164  and  166  which engage the sets of ribs  154  and  156  to provide a rotational key between the sleeve  150  and the container  158 . 
     The upper portion of the shaft  130  includes a shoulder  133  which supports a ratchet member  168  which is rotatable with respect to the shaft  130 . The ratchet member  168  includes an upper boss  170  which engages in an arcuate track  172  (FIG. 28A) in the underside of the cap  104  to provide a lost motion connection between the cap  104  and the ratchet member  168 . 
     As is illustrated in FIG. 28, the cap  104  is removable from the rest of the housing  100  to enable the assembled cartridge  108  (as shown in FIG. 10) to be inserted into the housing  100  until the lower lugs  126  and  128  of the core  110  engage in corresponding sockets  174 ,  176  (FIG. 23) in the bottom of the housing  100  to provide a rotational key between the core  110  and the housing  100 . 
     As is illustrated in FIG. 28, the housing  100  includes an upper rebate  178  which cooperates with a downwardly projecting lug (not shown) in the cap  104  to provide stops which define the limits of allowable rotational movement of the cap  104  relative to the rest of the housing  100 . 
     The lugs  126  and  128  space the lower end of the core  110  from the housing  100 , thereby enabling the interior of the core  110  to communicate with an air inlet  180  provided in the underside of the mouthpiece  102 , which includes an air outlet  182  partitioned from the inlet  180 . The container  158  is spaced from the housing  100  so as to provide an outlet passage between vertical inner ribs  182  and  184  (FIG. 29A) which communicates with the outlet  182 . 
     Thus the inhaler includes an airway, indicated by the marked arrows, extending from the air inlet  180  up through the core  110 , through the aperture  124  and a dose containing through-bore in registry therewith and then through the outlet passage down to the outlet  182 . In order to take a dose of medicament from the inhaler, the user must rotate the cap  104  from one to the other of its end positions and back again, causing the pin  144  to rupture the foil seal for a through bore and causing the through bore subsequently to be moved into registry with the outlet passage. This operation will now be described in greater detail with reference to FIGS. 29A-29F, and FIGS. 30A-30F. 
     FIG. 29A shows the dispenser in a initial condition in which the pin  144  is retracted and all the compartments are sealed. Rotation of the knob  104  in a clockwise direction as indicated by the arrow  184  of FIG. 29B causes a corresponding rotation of the shaft  130  which, in turn, rotates the crank arm  138  so as to extend the pin  144  until it penetrates the inner seal of a cavity  186  (FIG.  30 B). During this process, the slot  172  travels relative to the pin  170  so as to prevent rotation of the ratchet member  168  until the pin  170  engages the trailing end of the slot  172 . Further rotation of the knob  104  in the same direction then also causes a corresponding rotation of the member  168  which can rotate relative to the sleeve  150  in a clockwise direction only. As this happens, the engagement of the tang  116  with the serrated inner edge of the sleeve  150  prevents the latter from rotating in an anticlockwise direction. When the limit of allowable clockwise rotation is reached, the member  168  is in the position shown in FIG.  29 C and the pin  144  is in the position shown in FIG. 30C in which it extends through and beyond the bore  186  so as to pierce both inner and outer seals. 
     The knob  104  is then rotated in the opposite direction as shown in FIG. 12 d , causing the pin  144  to be withdrawn from the bore  186 . During the withdrawal of the pin  144 , the slot  172  moves relative to the boss  170  so as to prevent corresponding movement of the sleeve  150  (and hence the container  158 ) until the pin  144  has been fully withdrawn. Further anticlockwise rotation of the knob  104  rotates the member  168 , through the engagement of the boss  117  slot  172 , in turn causing rotation of the sleeve  150 . Since the latter is rotationally keyed to the container  158 , this movement causes the container  158  to rotate on the lower portion  118  of the core  110 , which in turn moves the through bores including the bore  186  along a part helical path as a result of the engagement of the cap  160  with the screw thread  122 . By the time the knob  104  has reached the limit of allowable anticlockwise rotation, as illustrated in FIG. 29F, the bore  186  is in registry with the outlet passage (FIG.  30 F). 
     If the user then inhales through the outlet  182  of the mouthpiece  102 , the consequent airflow through the device expels medicament from the bore  186 , in to the outlet chamber and out through the outlet  182 . 
     With reference to FIG. 23, the mouthpiece  102  also includes a grille  190  for capturing any loose fragments of the sealing foil which come adrift during inhalation. 
     The pin  144  is of the kind shown in FIGS. 31 and 32, and is so shaped as to create flaps in the foil seals whilst minimising the amount of material ejected from compartments during insertion. Those flaps are able to move, to allow material to be discharged, but are connected to the rest of the foil so as to reduce the chances of foil fragments breaking free during inhalation. 
     An alternative type of container for powdered medicament is shown in FIG. 33, and comprises a single rigid plate  350  having a central line of ten apertures such as the aperture  352 , each of which contains a respective dose of medicament. The apertures are sealed by two strips of foil, one of which is denoted by reference  354  which extend along opposite of the plate  350 . The medicament containing holes are flanked by two  356  and  358  of further holes which help to locate the plate  350  in use. 
     The central holes in the plate  350  can be filled by the apparatus shown in FIGS. 3-21, when modified so that the number and position of holes in the hopper at the filling station correspond to the number and position of holes in the central line in the container  350 . The modified apparatus lacks the rolling station  9  of the previously described apparatus.