Abstract:
An autoinjector comprising:
       a first chamber for containing a dry component of a medicament;   a second chamber for containing a wet component of a medicament;   an axially-slidable stopper intermediate said first and second chambers;   an injection needle in fluid communication with said first chamber; and   a transfer needle initially disposed axially forward of said stopper, the transfer needle having a longitudinal axial bore therethrough, a closed forward or proximal end, an open rear or distal end and a radial aperture intermediate said proximal and distal ends and in fluid communication with said longitudinal axial bore;   wherein said transfer needle is capable of penetrating said stopper to establish fluid communication between said first and second chambers via said bore and radial aperture to enable said wet component to mix with said dry component and wherein said injection needle is capable of delivering the mixed dry and wet components of the medicament to an injection site.

Description:
[0001]    This invention relates to the field of autoinjectors for the administration of liquid medication. 
       BACKGROUND 
       [0002]    An autoinjector is an automatic injection device designed to facilitate automated delivery of a dose of medicament to a patient through a hypodermic needle, the injection usually being administered by the patient themselves. The injection can be delivered subcutaneously or intra-muscularly, depending upon the properties of the autoinjector. An autoinjector works by delivering an injection automatically upon actuation by the patient, for example pressing a button, moving a lever or part of a housing etc. This is in contrast to a conventional manual syringe where the patient himself needs to directly depress a plunger into a barrel containing medicament in order to effect the injection. The terms “autoinjector” and “injection device” are used interchangeably in the following description. 
         [0003]    Some types of medication for delivery by an autoinjector are provided and stored in a two-part form, having a solid component and a liquid component, for example as a powdered medicament and a liquid solvent. The powdered medicament may comprise a ground-down or milled solid medicament or may be a powder prepared by a lyophilisation process for example. The liquid part may be a second medicament, rather than a solvent or diluent. Such two-part formulations are well known and sometimes referred to as “wet-dry” formulations. Immediately before the medicament is delivered by injection into the patient, the wet and dry components of the formulation are mixed together so that a combined medicament is delivered by the autoinjector. 
         [0004]    During storage and before use of the autoinjector, it is essential that the wet and dry components of the formulation are kept separate from one another within the autoinjector. When it is desired to deliver an injection, the wet and dry components need to meet together quickly and effectively before being expelled from the injection device. 
         [0005]    A prior art autoinjector is described in EP0361668 (Medimech Limited) in which an autoinjector has at least two chambers containing different ingredients of a medicament separated by an impermeable membrane. When it is desired to deliver an injection, a lance moves to cut or pierce the membrane allowing the ingredients to mix immediately before a plunger drives a needle out of the body of the injector to discharge the medicament through the needle. 
         [0006]    Another autoinjector is described in WO02/49691 (Gillespie) in which a spring-operated plunger forces pressurised liquid from a first chamber causing a releasable seal between the first and a second chamber to disengage so that liquid can flow through the second chamber dissolving any dry medicament therein. 
         [0007]    Another autoinjector is described in EP1709984 (Meridian Medical Technologies, Inc) in which the liquid is pressurised upon actuation of the device such that a fluid passageway between first and second chambers is opened in order that the wet and dry components can meet. In an alternative embodiment, a seal between the first and second chambers is punctured by a spike, allowing their respective contents to mix. 
         [0008]    In all three of the above prior art devices, mixing of the medicament is effected almost simultaneously with expulsion of the medicament from the device, the wet component being “flushed” through the dry component on its way out of the autoinjector. This has the advantage of reducing the total time between the user actuating the device and delivery of the injection. 
         [0009]    It is an object of the present invention to provide improved means for reconstituting wet and dry medicament components. 
       BRIEF SUMMARY OF THE DISCLOSURE 
       [0010]    In accordance with the present invention there is provided an autoinjector comprising:
       a first chamber for containing a dry component of a medicament;   a second chamber for containing a wet component of a medicament;   an axially-slidable stopper intermediate said first and second chambers;   an injection needle in fluid communication with said first chamber; and   a transfer needle initially disposed axially forward of said stopper, the transfer needle having a longitudinal axial bore therethrough, a closed forward or proximal end, an open rear or distal end and a radial aperture intermediate said proximal and distal ends and in fluid communication with said longitudinal axial bore;   wherein said transfer needle is capable of penetrating said stopper to establish fluid communication between said first and second chambers via said bore and radial aperture to enable said wet component to mix with said dry component and wherein said injection needle is capable of delivering the mixed dry and wet components of the medicament to an injection site.       
 
         [0017]    Other features are described in the appended claims. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0018]    Preferred embodiments of the present invention will now be more particularly described, by way of example only, with reference to the accompanying drawings in which: 
           [0019]      FIG. 1  is a cross sectional side view of the autoinjector device, prior to use, with a front end cap in place; 
           [0020]      FIG. 2  is a partial cross sectional view of the autoinjector showing a detailed view of the transfer needle and front portion of the medicament cartridge; 
           [0021]      FIG. 3  is a cross sectional side view of the device of  FIG. 1  with the front end cap, front cap clip and needle shield removed; 
           [0022]      FIG. 4   a  is a partial cross sectional view of the rear of the autoinjector of  FIG. 1  prior to use; 
           [0023]      FIG. 4   b  is a partial cross sectional view of the rear of the autoinjector of  FIG. 4   a  immediately after the outer housing has been moved axially forward with respect to the reconstitution housing; 
           [0024]      FIG. 4   c  is a partial cross sectional side view of the rear of the autoinjector of  FIG. 4   b  immediately after the flexible hooks of the reconstitution ram have flexed radially inwards; 
           [0025]      FIG. 4   d  is a partial cross sectional side view of the rear of the autoinjector of  FIG. 4   c  where the reconstitution ram is free to advance axially forward with respect to the cartridge; 
           [0026]      FIG. 5  is a cross sectional side view of the autoinjector device of  FIG. 4   d  after the reconstitution ram has driven the cartridge and needle axially forward to deliver medicament; 
           [0027]      FIG. 6   a  is a cross sectional side view of the autoinjector device of  FIG. 5  immediately after the transfer needle has punctured the first stopper; 
           [0028]      FIG. 6   b  is a partial cross section showing a detailed view of the transfer needle and first stopper of  FIG. 6   a;    
           [0029]      FIG. 7  is a cross sectional side view of the autoinjector device of  FIG. 6   a  when the second stopper has met the first stopper; 
           [0030]      FIG. 8  is a cross sectional side view of the autoinjector of  FIG. 7  after the first stopper and second stopper have travelled to the forward end of the cartridge and all transferable medicament has been delivered; and 
           [0031]      FIG. 9  is a simplified cross sectional side view of an alternative embodiment of the autoinjector device, having a dual-purpose needle which is shown ready to deliver medicament. 
       
    
    
     DETAILED DESCRIPTION 
       [0032]    Throughout this application, the words “comprise” and “contain” and variations of the words, for example “comprising” and “comprises”, means “including but not limited to”, and is not intended to (and does not) exclude other components, integers or steps. 
         [0033]    Throughout this application, the singular encompasses the plural unless the context otherwise requires. In particular, where the indefinite article is used, the specification is to be understood as contemplating plurality as well as singularity, unless the context requires otherwise. 
         [0034]    Throughout this application, reference to a “forward” direction means the direction which is towards the patient when the injection device is in use. The “forward” or “proximal” end of the injection device is the end nearest the patient&#39;s skin when the device is in use. Similarly, reference to a “rearward” direction means the direction which is away from the patient and the “rearward” or “distal” end of the device is the end furthest from the patient&#39;s skin when the injection device is in use. 
         [0035]    Throughout this application, reference to a “wet component of the medicament” means any liquid medicament, solvent, diluent, gel or other substantially liquid component. “Wet” does not imply a complete absence of any solid matter. 
         [0036]    Throughout this application, reference to a “dry component of the medicament” means any solid, powder or other substantially dry component. “Dry” does not imply a complete absence of liquid, and the dry component may comprise a stiff paste or slurry for example. 
         [0037]    Throughout this application, references to “reconstitution” include the term “mixing” wherein components of a medicament are mixed together with no solution, reaction or other chemical process necessarily taking place. 
         [0038]    Features, integers, characteristics or groups described in conjunction with a particular aspect, embodiment or example of the invention are to be understood to be applicable to any other aspect, embodiment or example described herein unless incompatible therewith. 
         [0039]    In general, an autoinjector includes a needle which is located within the housing of the device. Upon activation of a force-generating source, a portion of the needle extends out of the housing and penetrates the outer layer of skin to deliver medicament. An improved autoinjector is described in our international patent application, published under number WO 2005/070481. This device requires that the needle is moved axially so that it can appear beyond the end of the nozzle for the duration of the injection, after which the needle retracts automatically, so that it is never in sight of the user. The device also requires that the plunger is moved axially so that medicament is ejected. The overall complexity of the autoinjector is significantly reduced by both of these requirements being effected by one component, namely an inner housing (having reference numeral 7 in WO 2005/070481). Whilst it is preferable that the autoinjector described herein comprises a mechanism whereby the needle extends from and retracts into the nozzle automatically, this is not an essential feature. 
         [0040]    Referring to  FIG. 1  of the present application, selected components of the autoinjector will now be described. The device has an outer housing  20  with a front end cap  21  on a front end thereof. Within the outer housing  20  and front end cap  21  there is a reconstitution housing  60  that contains a glass medicament cartridge  38 . The cartridge  38  in isolation is open at both ends and has a generally cylindrical body with a narrow neck region  38   b  at a front end. The forwardmost part of the neck region  38   b  has a flange  38   a  having a larger diameter than the neck region  38   b.    
         [0041]    A plastic moulding  37  is located in the neck region  38   b  of the cartridge  38  and forms a seal around its front opening. The plastic moulding  37  is affixed to the flange  38   a  of the cartridge  38  by several hooks  37   a  located around the circumference of the plastic moulding  37 . The seal is enhanced by an O-ring seal  39  located intermediate the flange  38   a  and the plastic moulding  37 . At least two tags  37   b  extend radially outwards from the plastic moulding  37  and locate in apertures (not shown) in the reconstitution housing  60  thereby fixing the location of the plastic moulding  37  (and therefore cartridge  38 ) relative the reconstitution housing  60 . 
         [0042]    When assembled, the cartridge  38  has a dry chamber  40  defined as the volume within the cartridge  38  intermediate the plastic moulding and a first stopper  41 . The dry chamber is for storage of the dry component of medicament. 
         [0043]    At the rear of the cartridge  38  a second stopper  42  is located axially rearward of the first stopper  41 . A wet chamber is then defined as the volume within the cartridge  38  intermediate the first stopper  41  and second stopper  42 . Both the first stopper  41  and second stopper  42  are slidably located within the cartridge  38  and can move along an axial path within the cartridge  38  whilst maintaining a seal. Thus the first stopper  41  provides a seal between the dry chamber  40  and wet chamber  50  and normally does not permit mixing of the dry and wet medicament components. 
         [0044]    Embedded in plastic moulding  37  are two needles, namely an injection needle  32  and a transfer needle  51 . The injection needle  32  extends forwardly from the plastic moulding  37  and is preferably coaxial with a central longitudinal axis  1  of the autoinjector device. The transfer needle  51  extends rearwardly from the plastic moulding  37  into the cartridge  38  and is offset radially from the central longitudinal axis  1  of the device. The transfer needle  51  is therefore also offset radially from the injection needle  32 , provided that the injection needle  32  is coaxial with central longitudinal axis  1 . 
         [0045]    The injection needle  32  is embedded in an open hole  37   c  within the plastic moulding  37  such that the injection needle  32  is in fluid communication with the dry chamber  40  (see  FIG. 2  for example). Conversely, the transfer needle  51  is embedded in a “blind hole”  39   b  within the plastic moulding  37 . 
         [0046]    As can be seen from  FIG. 2 , the transfer needle  51  has an axial bore  51   b  therethrough. The transfer needle  51  is open at its rearmost end so that the bore  51   b  is in fluid communication with the dry chamber  40  (prior to reconstitution), and is closed at its forwardmost end within the blind hole  39   b.  The transfer needle  51  is provided with a radial hole  51   a  at a point axially forward from the open rear end which extends the bore  51   b  in a radial direction. The radial hole is also in fluid communication with the dry chamber  40 . 
         [0047]    When assembling the device, the wet and dry medicament components must be installed into the cartridge  38 . The dry component is first placed in the front end of the cartridge  38  around the transfer needle  51 . Once the dry medicament has been placed in the cartridge  38 , the first stopper  41  can be installed, ensuring an air space remains in the dry chamber  40 . The air space permits the first stopper  41  to move forwards during actuation such that the transfer needle  51  can pierce it, as will be described further below. 
         [0048]    The first stopper  41  forms a seal between the dry chamber  40  and the remainder of the cartridge  38  such that the liquid medicament component can then be filled into the cartridge  38  without entering the dry chamber  40 . Once the liquid component has been filled into the cartridge  38 , the second stopper  42  is installed. At this point, the cartridge  38  and the medicaments contained therein are sealed at a front end by the plastic moulding  37  and at a rear end by the second stopper  42 . It is therefore important that conditions remain sterile at least until the second stopper  42  is installed. The forward end of the dry chamber  40  is in fluid communication with injection needle  32  that is embedded in plastic moulding  37 . Sterile conditions are maintained by a needle cover  33  that surrounds injection needle  32 , fitting into moulding  37  at a rear end and sealing the dry chamber  40 . The needle cover  32  is described further below. 
         [0049]    Once the medicament components have been loaded into the cartridge  38  and sealed therein, the cartridge  38  is installed into the reconstitution housing  60 .  FIG. 1  shows the autoinjector with the cartridge  38  installed prior to reconstitution. 
         [0050]    At the front end of the reconstitution housing  60  is a front housing  59  connected thereto by hooks  59   a.  The front housing  59  has an aperture  59   b  located centrally on the central longitudinal axis  1  through which the needle  32  can protrude when an injection is delivered. Surrounding the front housing  59  and a front portion of the reconstitution housing  60  is a front cap clip  72 . The front cap clip  72  has outwardly extending hooks (not shown) that locate in apertures (not shown) of the front end cap  21  affixing the front cap clip  72  thereto. 
         [0051]    For the user to use the device and deliver medicament, the front end cap  21  and front cap clip  72  must first be removed. Removal of the front end cap  21  exposes part of the reconstitution housing  60  since it projects from within the outer housing  20 . To remove the front end cap  21  a forward axial force must be applied to overcome the hooks of the front cap clip  72 . 
         [0052]    The reconstitution housing  60  has at least one guide channel  70  therein which may be an aperture or a groove or the like. The guide channel  70  is preferably helical and is illustrated in  FIG. 1  where it can be seen that the guide channel has a closed end  70   a  and an open end  70   b.  The front housing  59  also has at least one groove (not shown) that forms a continuation of the open end  70   b  of the at least one guide channel  70 . 
         [0053]    The guide channel  70  is adapted to receive at least one guide pin (not shown) projecting radially inwardly from an inner surface of the front cap clip  72 . Prior to use, the front end cap fits over the reconstitution housing  60  and the guide pin is disposed in the guide channel  70  and axial movement of the front cap clip  72  relative the reconstitution housing  60  is prevented. This feature prevents the front cap clip  72  from being removed when the front end cap  21  is pulled axially forward. 
         [0054]    It is possible to twist the front cap clip  72  relative the reconstitution housing  60 , but only in one direction as the guide pin is initially disposed adjacent the closed end  70   a  of the guide channel  70 . When the front cap clip  72  is twisted relative to the reconstitution housing  60 , the guide pin travels along the guide channel  70  so that the reconstitution housing  60  (and remainder of the device) moves axially relative to the front cap clip  72 . Thus, when the guide pin reaches the open end  70   b  of the guide channel  70 , the front cap clip  72  can be removed entirely from the device (the guide pin passing through the groove(s) in the front housing). 
         [0055]    In alternative embodiments, the front cap may be removed by pulling along a straight axial path. However, the helical guide channel arrangement described above is preferable as it prevents independent movement of the internal components of the device, which may lead to unintentional firing, for example if the device was dropped. 
         [0056]    Prior to use, the needle shield  33  surrounds the needle  32  thus protecting it from damage, ensuring it remains sterile, and preventing any potential injury to the user. The forwardmost end of the needle shield  33  extends through an aperture located on the central axis of the front cap clip  72 . A flanged end  33   a  of the needle shield  33  having a larger diameter than the aperture in the front cap clip  72  is disposed on a front side of the front cap clip  72 . Removal of the front cap clip  72  therefore causes the removal of the needle shield  33  also. In one preferable embodiment, a quarter of a turn is sufficient to remove the front cap clip  72  and the needle shield  33 . Once the front end cap  21 , front cap clip  72  and needle shield  33  have been removed, as shown in  FIG. 3 , the device is ready for use. 
         [0057]    The front of the device is then placed against an injection site and the outer sleeve  20  is pushed axially forward by the user to begin reconstitution. The mechanism by which reconstitution begins will be described with reference to  FIGS. 4   a - 4   d.    
         [0058]      FIG. 4   a  shows a cross sectional view of the rear of the device before the outer sleeve  20  is pushed axially forward. From  FIG. 4   a , it can be seen that the outer housing  20  has several hooks  20   b  that extends axially forward from an inner surface of a rear end  20   a.  When in the condition illustrated by  FIG. 4   a , the hooks  20   b  prevent forward axial movement of the reconstitution housing  60  relative the outer housing  20 , thus retaining the reconstitution housing  60  within the outer housing  20 . 
         [0059]    As shown in  FIG. 4   a , the reconstitution housing  60  has a narrow rear section  60   a  through which protrudes a reconstitution ram  61  (prior to use). The rear of the reconstitution ram  61  is generally cylindrical and has a plurality of flexible hooks  61   a  defined by axial slots  61   b  where the flexible hooks extend radially outwards to a diameter greater than that of the narrow section  60   a.  Thus, the flexible hooks  61   a  prevent forward axial movement of the reconstitution ram  61  relative the reconstitution housing  60 . Before reconstitution has been actuated by the user pushing the outer sleeve  20  axially forward, a reconstitution pin  13  is disposed within the flexible hooks  61   a  (as shown in  FIG. 4   a ). 
         [0060]    The reconstitution ram  61  extends axially forwards and connects to a reconstitution stopper  52  at a front end. Surrounding the reconstitution ram  61  within the reconstitution housing  60  is a spring  62 . In  FIG. 4   a , the spring  62  is shown to be under compression acting rearwardly against the rear of the reconstitution housing  60  and forwardly against reconstitution stopper  52 . 
         [0061]    The reconstitution pin  13  has a wide section  13   a  disposed axially forward of a narrow section  13   b.  Both the wide section  13   a  and the narrow section  13   b  are generally cylindrical where diameter of the wide section  13   a  is larger than that of the narrow section  13   b.  When the outer housing  20  is pushed axially forwards (indicated by arrow in  FIG. 4   b ), the rear of the outer housing  20  abuts the reconstitution pin  13  also causing it to move axially forwards to the position shown in  FIG. 4   b . When the wide section of the reconstitution pin  13  has passed the narrow section  60   a  at the rear of the reconstitution housing (as shown in  FIG. 4   b ) the flexible hooks  61   a  are free to flex radially inwards so that their axial path is no longer blocked by the narrow section  60   a  of the reconstitution housing  60  ( FIG. 4   c ). The flexible hooks  61  a may have a chamfered leading edge to assist them in flexing radially inwards. Since the flexible hooks  61   a  (when flexed radially inwards) no longer prevent forward axial movement of the reconstitution ram  61  relative the reconstitution housing  60 , the reconstitution ram  61  is free to move axially forwards under the influence of the spring  62 . 
         [0062]    The frontmost edge of the forwardly advancing outer sleeve  20  causes the tags  37   b  of the plastic moulding  37  located in apertures (not shown) of the reconstitution housing  60  to dislocate from their apertures thereby permitting movement of the plastic moulding  37  (and therefore cartridge  38 ) relative the reconstitution housing  60 . 
         [0063]    The forwardly advancing reconstitution ram  61  forces the reconstitution stopper  52  to advance forwards which abuts the second stopper  42  causing it too to move axially forwards. Due to the force of spring  62 , the advancing reconstitution ram  61  causes the cartridge  38 , plastic moulding  37  and injection needle  32  to move axially forwards also. As the cartridge  38  travels to the forward most end of the reconstitution housing  60 , the plastic moulding  37  abuts the front housing  59  and the injection needle  32  projects through the aperture  59   b  of the front housing  59  to penetrate an injection site ( FIG. 5 ). The needle is now ready to deliver medicament. 
         [0064]    As a result of the plastic moulding  37  being in abutment with the front housing  59 , the cartridge  38 , plastic moulding  37 , and injection needle  32  cannot move axially forward any further. Since the spring  62  has not yet been fully decompressed, the elastic spring force continues to act through the reconstitution ram  61 . This causes the reconstitution stopper  52  and second stopper  42  to collectively move axially forward relative to the cartridge  38 . Due to the incompressible nature of the liquid medicament contained within the wet chamber  50 , the forward axial movement of the second stopper  52  drives the first stopper  41  axially forward a substantially identical distance. The first stopper  41  therefore moves axially forward relative to the cartridge  38  and is pierced by the transfer needle  51 . The above mentioned air space in the dry chamber  40  permits forward axial movement of the first stopper  41  relative the cartridge  38 . Without an air space, the first stopper  41  would not move axially forward relative the cartridge  38  due to the substantially incompressible dry medicament therein. 
         [0065]    As the transfer needle penetrates the first stopper  41 , fluid communication between the wet chamber  50  and the dry chamber  40  is established via the bore  51   b  and radial hole  51  a of the transfer needle  51 .  FIG. 6   a  shows the device immediately after fluid communication between the wet chamber  50  and the dry chamber  40  has been established.  FIG. 6   b  provides a more detailed view of the transfer needle  51  and first stopper  41  as shown in  FIG. 6   a . The liquid medicament component then flows from the wet chamber  50  into the dry chamber  40  and mixes with dry medicament component before exiting the dry chamber  40  through the injection needle  32 . This process is known in the art as “flush through” mixing. Depending on the solubility of the dry medicament, the liquid exiting the injection needle will be a solution. In an alternative embodiment, a filter may be disposed in the open hole  37   c  of the plastic moulding  37  to prevent solid matter from entering the injection needle  32  and potentially causing a blockage. Use of a filter may also aid mixing as solid medicament would be held on the filter surface whilst the liquid medicament flushes through. 
         [0066]    The rate of flow from the wet chamber  50  to the dry chamber  40  is limited by the dimensions of the transfer needle  51 . In particular, the rate of flow can be controlled from a design perspective by altering the diameter of the transfer needle  51  (and its bore  51   b ), and the size and position of the radial hole  51   a.  In an alternative embodiment, the transfer needle  51  may comprise one or more holes that are not necessarily radial holes, through which the wet medicament component can flow from the wet chamber  50  to the dry chamber  40 . 
         [0067]    In a further embodiment, the dry chamber  40  may include baffles that manage the flow of liquid medicament and enhance mixing of the wet and dry components. 
         [0068]    Liquid medicament will continue to flow from the wet chamber  50  to the dry chamber  40  through transfer needle  51  until the second stopper  42  meets the first stopper  41 .  FIG. 7  shows the device immediately after the second stopper  42  has made contact with the first stopper  41 . At this point, the liquid medicament has been expelled from the wet chamber  50 . It should be noted that, owing to the geometry of the first and second stoppers  41 ,  42 , some liquid medicament may remain in the wet chamber  50 . The spring  62  continues to act axially forward pushing the reconstitution ram  61 , reconstitution stopper  52 , second stopper  42  and first stopper  41  collectively forward relative the cartridge  38 . As this happens, the first stopper  41  slides over the transfer needle  51  until it cannot move axially forward any further with the cartridge  38 . This action expels the remaining transferable mixed medicament from the dry chamber  40  through the injection needle  32  and the injection is completed. 
         [0069]    During injection, the dry chamber  40  is vented through the injection needle  32 , so the air space in the dry chamber  40  also permits some flow of liquid medicament between the particles of the dry medicament. 
         [0070]      FIG. 8  shows the device when the first stopper  41  has been pushed to its forwardmost position with the cartridge  38 . It will be noted from  FIG. 8  that due to the shape of the cartridge  38 , the dry chamber  40  will not be reduced to a zero volume when the first stopper  41  is in its forwardmost position within the cartridge  38 . This is important with regards to the position of the radial hole  51   a . While the radial hole  51   a  may be located anywhere on the transfer needle  51 , it is preferable that it is located such that it is not blocked by the advancing first stopper  41  at any stage during its axial movement. Thus, a preferable location for the radial hole  51   a  is on a part of the transfer needle  51  that always remains within the dry chamber  40  (and not embedded in the first stopper  41 ) when the first stopper  41  has advanced to the front of the cartridge  38 . 
         [0071]    Since the dry chamber  40  is not reduced to a zero volume when the first stopper  41  has travelled its full forward distance within the cartridge  38 , some medicament may remain within the dry chamber  40  after the injection process is complete. However, this can be compensated for by careful selection of the quantities of medicaments initially loaded into the device. 
         [0072]    In alternative embodiments, means may be provided for automatically retracting the needle  32  into the reconstitution housing after medicament has been delivered, or after a suitable dwell time. In other embodiments, the needle  32  may also be driven forward by driving means to deliver an injection such that pressurisation of the liquid medicament component in the wet chamber  50  would not necessarily be required. 
         [0073]    In a further embodiment shown in  FIG. 9 , one needle is provided which serves the functions of both the transfer needle  51  and the injection needle  32 . Such a dual-purpose needle may comprise a double-ended needle  101  having a crimp or other blockage  101  part-way down and a radial hole  102 ,  103  on each side of the blockage.  FIG. 9  shows the device in a comparable position to the device shown in  FIG. 5 , i.e. with the needle  100  ready to deliver an injection but with the medicament not yet mixed. The forwardmost radial hole  102  is equivalent to the open rear end of needle  32  in  FIG. 5  and allows the needle  100  to be in fluid communication with the dry chamber  40 . The rearmost radial hole  103  is equivalent to the radial hole  51   a  described above. The blockage  101  is equivalent to the closed end of transfer needle  51  described above. The relative spacing of the blockage  101  and radial holes  102 ,  103  in relation to the stopper  41  allows the dual-purpose needle  100  to function in the same manner as both the injection needle  32  and transfer needle  51  described above. 
         [0074]    The reader&#39;s attention is directed to all papers and documents which are filed concurrently with or previous to this specification in connection with this application and which are open to public inspection with this specification, and the contents of all such papers and documents are incorporated herein by reference. 
         [0075]    All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and/or steps are mutually exclusive. 
         [0076]    Each feature disclosed in this specification (including any accompanying claims, abstract and drawings), may be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features. 
         [0077]    The invention is not restricted to the details of any foregoing embodiments. The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.