GB2447787A

GB2447787A - An autoinjector that mixes wet and dry medicament components when moved relative to its packaging

Info

Publication number: GB2447787A
Application number: GB0805269A
Authority: GB
Inventors: Kevin Stamp; Ian Charles Cleathero
Original assignee: Medical House PLC
Current assignee: Medical House PLC
Priority date: 2007-03-21
Filing date: 2008-03-20
Publication date: 2008-09-24
Also published as: WO2008114035A1; GB0705388D0; GB0805269D0

Abstract

An autoinjector includes a first chamber 40 for containing a dry component of a medicament, and a second chamber 50 for containing a wet component of a medicament and reconstitution means for mixing said dry and wet components by placing said first 40 and second 50 chambers into fluid communication with one another, the autoinjector is in packaging 10 adapted to automatically actuate said reconstitution means to mix said dry and wet components upon movement of a part thereof relative to a part of the autoinjector. Further an autoinjector may have reconstitution means that is capable of pressurising a wet component of the medicament such that upon entry into a chamber a stopper is moved axially.

Description

IMPROVED AUTOINJECTOR

This invention relates to the field of autoinjectors for the administration of liquid medication.

BACKGROUND

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.

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 S...

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.

: During storage and before use of the autoirijector, 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.

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.

Another autoinjector is described in W002/4969i (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.

Another autoinjector is described in EP1709984 (Meridian Medical Technologies, mc) 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.

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. However, potentially there is a disadvantage in such flushing" action, for example if mixing of the components is not homogenous, or if some of the dry *., 25 component is left behind inside the device. Incomplete mixing can also result in a blockage of the injection needle. S...

Generally, in a wet-dry autoinjector, the dry chamber containing the solid medicament *:. powder also contains a volume of air or other gas which is replaced by the liquid medicament entering therein when the medicament is reconstituted or mixed. Any *...

excess gas has to be "bled" from the chamber before injection takes place, else the device would undesirably inject an unacceptable volume of gas into the patient as well as the reconstituted medicament. In addition, excess gas in the chamber may cause bubbling or foaming during mixing and/or injection (again with the risk of injecting unwanted gas into the patient). Bleeding excess gas from the chamber prior to injecting the medicament increases the total operating time of the device, which may be undesirable in an emergency situation, or where the patient is needle-phobic, and it is advantageous to effect the injection as quickly as possible.

SUMMARY OF THE INVENTION

According to a first aspect of the invention there is provided an autoinjector kit comprising an autoinjector including: a first chamber for containing a dry component of a medicament, and a second chamber for containing a wet component of a medicament; reconstitution means for mixing said dry and wet components by placing said first and second chambers into fluid communication with one another, packaging; wherein said packaging is adapted to automatically actuate said reconstitution means to mix said dry and wet components upon movement of at least a part thereof relative to at least part of the autoinjector.

The packaging of a conventional autoinjector normally has no function other than to protect and possibly seal the autoinjector during storage and transport, and is often simply discarded before using the autoinjector. At least part of the packaging is moved, usually by the user, to activate reconstitution before an injection of medicament can be delivered. If the movement required to actuate the reconstitution means occurs during the opening of the packaging, the components of the medicament can be mixed rapidly * ,. 25 and without the need for a separate positive action or intervention by the user who may :.:: be in a stressful situation and requiring the autoinjector to be ready for use as quickly as S...

possible. In some situations and depending upon the properties of the medicament : concerned, it may be possible to reconstitute the medrcament as described above but then to delay delivery of the injection, for example by a few hours. Priming the device by reconstituting the medicament in advance may make the delivery of a medicament : injection, when required, even quicker and simpler to perform in an emergency situation.

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According to a second aspect of the invention there is provided a method of reconstituting a two-part medicament comprising the steps of: providing an autoinjector kit as described in any of the preceding paragraphs; and moving said at least part of said packaging relative to at least part of the autoinjector so as to actuate said reconstitution means.

According to a further aspect of the invention there is provided an autoinjector including: a first chamber for containing a dry component of a medicament, and a second chamber for containing a wet component of a medicament; an axially-moveable stopper intermediate the first and second chambers; reconstitution means for mixing said dry and wet components by putting said first and second chambers into fluid communication with one another; wherein said reconstitution means is capable of pressurising said wet component so that, upon entry of the pressurised wet component into said first chamber, hydraulic forces cause said axially-moveable stopper to move so as to increase the volume of said first chamber to accommodate said wet component.

The first chamber containing the dry component is preferably initially provided with little or no gas therein, as the stopper is axially-positioned to abut the dry component which may be packed in place. When the reconstitution means is actuated, the stopper moves axially only enough to increase the volume of the first chamber sufficiently to accommodate the wet component entering therein. Therefore, throughout, the volume of unwanted gas in the chamber is kept to a minimum, reducing the likelihood of bubbling or foaming during mixing, and reducing the volume of gas which may eventually be undesirably injected into the user. Furthermore, the reconstitution stage is effected automatically by the hydraulic forces present in the pressurised wet component, without requiring any intervention or action by the user once it has been initiated. S... * . * SSS

Further features of the invention are defined in the appended claims. S...

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BRIEF DESCRIPTION OF THE DRAWINGS *5I*

*..: 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: Figure 1 is an exploded view of the autoinjector kit components; Figure 2 is a cross-sectional view of the autoinjector kit, in its storage condition; Figure 3 is a cross-sectional view of the autoinjector kit, with the proximal pin wedge removed and the mixing stage in process; Figure 4 is a cross-sectional view of the autoinjector, with the medicament fully mixed and the injection ready to be delivered; Figure 5 is a cross-sectional view of the autoinjector, during delivery of the injection; Figure 6 is a cross-sectional view of the autoinjector, after delivery of the injection is complete with the needle still exposed; Figure 7 is a cross-sectional view of the autoinjector, after delivery of the injection and retraction of the needle; In Figures 4-7, the autoinjector's internal springs are not illustrated, to improve clarity.

Figure 8 is a perspective view of a second embodiment of the autoinjector kit in which the packaging need not be removed from the device before delivery of a medicament; Figure 9A shows the autoinjector kit of Figure 8 part-way through twisting the end cap relative to the main packaging section; Figure 9B, drawn to a larger scale, shows internal detail of the rear part of the main packaging section and autoinjector therein; * ** * * * * ** Figure 1OA shows the autoinjector kit of Figure 8 further through twisting the end cap S...

relative to the main packaging section; *5** S...

Figure lOB drawn to a larger scale, shows internal detail of the rear part of the main packaging section and autoinjector therein, with the guide ribs 86 abutting endstops 88; a...

Figure 11 shows the autoinjector kit of Figure 8 with the end cap 11 removed from the main packaging section; Figure 12 shows the autoinjector placed against an injection site, ready to administer an injection of medicament; and Figure 13 shows an alternative embodiment of an autoinjector including a double ended ufloating needle" disposed between the dry and wet medicament chambers.

DETAILED DESCRIPTION

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.

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.

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 "distal" end of the injection device is the end nearest the patient'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 "proximal" end of the device is the end furthest from the patient's skin when the injection device is in use.

Throughout this application, reference to a "wet component of the medicament" means *.. 25 any liquid medicament, solvent, diluent, gel or other substantially liquid component.

:.:: "Wet" does not imply a complete absence of any solid matter. *..

Throughout this application, reference to a "dry component of the medicamerit" 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 I...

for example.

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Throughout this application, reference to "packaging" means the packaging inside which the autoinjector is normally stored, transported and/or provided to the user and which needs to be opened, manipulated and/or removed before the autoinjector can be used.

The packaging may be separable from the working components of the autoinjector and may be disposable. Alternatively, at least part of the packaging may form part of the working components of the autoinjector. The packaging may also serve to provide a sterile barrier for the autoinjector and the medicament contained therein.

Throughout this application, reference to "opening" of the packaging means manipulating, removing or otherwise acting on said packaging so that the autoinjector is no longer in its storage condition. Once the packaging is opened, it may not be possible to safely re-close the packaging and store the autoinjector for future use, although it is envisaged that, in some embodiments, it may be possible to re-close the packaging after reconstitution has taken place to store the autoinjector for future delivery of medicament.

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.

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.

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 *,* 25 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 S... . . . . : 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 overali complexity of the autoinjector is significantly reduced by both of these S...

requirements being effected by one component, namely an inner housing (having reference numeral 7 in WO 2005/070481).

Referring to Figures 1 and 2 of the present application, selected components of the autoinjector will now be described. The device is stored, transported and provided to the user inside a cylindrical outer packaging tube 10, sealed with an outer tube end cap 11 and 0-ring 12. Unusually, the outer packaging tube 10 (which may be referred to as "secondary packaging") includes part of the means for actuating the reconstitution or mixing stage for the dry and wet components of the medicament. The rear end of the outer packaging tube 10 is provided with an inwardly-directed rear pin wedge 13 (shown in Figure 2) whose function will be described later.

Immediately inside the outer packaging tube 10 are the outer housing 20 of the device and its front end cap 21. The outer housing 20 is similar in function to the outer housing described in WO 2005/070481.

inside the outer housing 20 is the rear housing 30 which has various slots and other guide means therein for controlling the path of other components during delivery of an injection. The rear housing 30 is attached to a front housing 31 which covers and conceals the injection needle 32.

The dry component of the medicament is stored in the front chamber 40a of a dry medicament chamber 40. Dry chamber 40 has two chambers 40a and 40b which are separated and sealed from one another by an axially-moveable stopper 41. The rear chamber 41b initially contains air or other gas. The front chamber 40a is full, with the stopper 41 abutting the dry component. In this way, the initial volume of unwanted gas in the chamber is minimised and is usually limited only to the small volume of gas located between the particles of the dry component.

The wet component of the medicament is stored in a wet medicament chamber 50. The , 25 wet chamber has a needle 51 at its front end which is staked into (but not through) the stopr 41 of the dry chamber. The staked needle 51 provides a seal between the wet *S..

and dry chambers. The rear of the wet chamber 50 is sealed by an axially-moveable :r stopper 52.

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Reconstitution of the medicament is effected by a reconstitution housing 60, *S..

: reconstitution ram 61 which abuts the rear wet chamber stopper 52 and a reconstitution spring 62 which biases the ram 61 forwardly. In the storage position illustrated in Figure 2, it can be seen that the ram 61 has rearwardly extending flexible fingers 61A which are wedged apart by pin wedge 13. The wedged-apart flexible fingers 61A cannot pass the narrowed potion 60A of the reconstitution housing, despite being forwardly-biased by the spring 62.

Expulsion of the medicament from the device is effected by an injection ram 70 which, in use, abuts the dry chamber stopper 41.

For controlling delivery of the injection, an inner housing 80 and compression pad 81 are provided which are comparable to inner housing 7 and syringe holder 100 described in WO 2005/070481 and our co-pending application number PCT/GB2007/000141 respectively. These components form part of the injection delivery means.

The function of these components will now be described with reference to Figures 2-7.

ifl its storage condition (see Figure 2) the internal components of the autoinjector, in particular the reconstitution components, are unable to move axially because of the presence of pin wedge 13 inwardly-directed from the rear of the outer packaging tube 10.

When the user is ready to actuate the device, he pulls off the outer tube cap 11 and tips the device forward and out of the outer packaging tube 10. As soon as he does this, reconstitution of the medicament can begin with the reconstitution ram 61 being tipped off the pin wedge 13 so that, as shown in Figures 3 and 4, the fingers 61A are now free to flex radially-inwardly so that they can pass narrowed portion 60A under the force of spring 62. Forward movement of the reconstitution ram 61 pushes the stopper 52 forward onto the incompressible liquid in the wet chamber 50 so that the whole wet chamber 50 moves axially forwards. This causes the needle 51 staked in the dry chamber stopper 41 to be driven right through to puncture the stopper creating a fluid connection between the wet and dry chambers. * * S...

Referring now to Figure 4, the wet component of the medicament which is under *.*. . . : pressure from the forward moving reconstitution ram 61 is forced through the needle 51 into the dry chamber 40a. Hydraulic forces and turbulence in the incoming wet component contributes to and facilitates its mixing with the dry component. The wet component enters the dry chamber 40a, displacing any gas present between the dry ** component particles. Note that the injection needle 32 is not in fluid communication with the medicament chamber 40a because its rear end is inside a needle housing 33. As the chamber 40a fills with reconstituted medicament, the stopper 41 starts moving axially-rearwardly, slipping over needle 51 until the full volume of wet component has been transferred from the wet chamber 50 to the chamber 40a. In this way, not only does little or no unwanted gas remain in the chamber 40a, but once the reconstitution stage is complete (as shown in Figure 4), the volume of the chamber 40a has increased only to the minimum volume required to contain the reconstituted medicament, ready for expulsion from the device.

Using this improved autoinjector, the reconstitution of the medicament (which for example might take only 2-3 seconds depending upon the characteristics of the medicament) takes place whilst the user is removing the secondary packaging (10, 11, 12, 13) and moving the device to the injection site. Thus, a separate mixing stage occurs which is distinct from the medicament delivery stage, (unlike the "flushing"-type action of the prior art devices simultaneous with the injection), but without need for the user to positively actuate and then wait for the mixing to take place. Furthermore, the reconstituted medicament ends up in a chamber of the minimum volume necessary.

Once the medicament is reconstituted, an injection delivery mechanism takes over which has similarities with that described in WO 2005/070481. Figure 4 shows the medicament fully mixed and ready for delivery. When it is desired to deliver an injection, the user removes the front end cap 21 from the device in the direction indicated by the arrow in Figure 4 and places the front housing 31 of the device on the skin at the injection site, grasping the outer housing 20.

Referring to Figure 5, application of forward force F to the outer housing 20, actuates the main energy source of the device (usually a spring, not illustrated in Figure 5), causing the inner housing 80 (comparable to inner housing 7 in WO 2005/070481) to drive the ** 25 needle forwardly out of the device (through an aperture or septum) in the front housing and into the injection site. This comprises the "first position' of the inner housing S..

described in WO 2005/070481. At or around the same time, the rear end of the injection needle 32 punctures a septum or the like between the rear of the needle housing 33 and the chamber 40a, bringing the needle 32 into fluid communication with the medicament chamber 40a. S... S...

. Next, referring to Figure 6, the injection ram 70 is driven forward by the inner housing 80, pushing the stopper 41 into the reconstituted medicament in the chamber 40a so as to drive the medicament out of the device through needle 32. This comprises the "second position" of the inner housing described in WO 2005/070481.

Referring to Figure 7, once the medicament has been delivered, the inner housing 80 causes the needle 32 to retract back into the front housing 31 so that it is completely concealed from the user. This comprises the uthird position" of the inner housing described in WO 2005/070481.

Figures 8-12 show an alternative embodiment in which it is not necessary to fully remove the outer packaging in order to reconstitute the medicament. The reconstitution process is nevertheless similar to that described above, (i.e. removal of pin wedge 13 from flexible fingers 61a) and is activated upon opening the packaging.

Figure 8 shows an autoirüector stored within an outer packaging tube 10' having an outer tube end cap 11'. A guide pin 84 will be described below. When it is desired to open the packaging, the end cap 11' can be twisted with respect to the packaging tube 10', in the direction indicated by the arrow in Figure 8.

Referring now to Figure 9A, the tube end cap 11' comprises a main section 1 la' and a spigot 11 b'. The spigot section 11 b' has a smaller diameter than the main section and normally fits inside the packaging tube 10'. The spigot lib' has at least one guide channel 82 therein which may be an aperture or a groove or the like. The guide channel 82 is preferably helical and is illustrated more clearly in Figure 11 where it can be seen that the channel 82 has an open end 82a and a closed end 82b.

Turning back to Figure 9A, the guide channel 82 is adapted to receive at least one guide pin 84 projecting radially inwardly from an inner surface of the packaging tube 10'.

25 When the device is in a stored condition, the packaging tube 10' fits over the spigot section lib' and the guide pin 84 is disposed in the guide channel 82 and axial movement of the packaging tube 10' relative to the end cap 11' is prevented.

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It is possible to twist the packaging tube 10' relative to the end cap 11', but only in one direction as the guide pin 84 is initially disposed adjacent the closed end 82b of the *...

: guide channel 28. When the packaging tube 10' is twisted relative to the end cap 11', *. the guide pin 84 travels along the guide channel 82 so that the packaging tube 10' moves axially relative to the end cap 11'. The autoinjector 90 contained within the packaging tube remains stationary relative to the end cap 11'. Consequently, there is relative axial movement between the autoirijector 90 and the packaging tube 10'.

The effect of this relative axial movement is illustrated with reference to Figures 9B and I OB. The rear end of the autoinjector 90 comprises rearwardly-projecting ramps 88 which are preferably helical and have the same pitch as the guide channel 82 on the end cap 11'. The rear end 1 Oa' of the packaging tube 10' has inwardly-projecting guide ribs 86 that project towards the front of the autoinjector. A pin wedge 13, similar to that described above in relation to the first embodiment, is located centrally of the guide ribs 86, projecting towards the front of the autoinjector and holding apart flexible fingers 61 a.

When the autoinjector is in its storage condition (as in Figure 8) wherein the packaging tube 10' is securely fastened to the end cap 11', the forwardmost extremities of the guide ribs 86 are at the bottoms of the ramps 88 so that the distance between rear end of the autoinjector 90 and the inner surface of the rear end lOa' of the packaging tube 10' is substantially equal to the length of the guide ribs 86. Relative axial movement of the autoinjector and the outer packaging tube is not possible as there is no axial space in which such movement could occur.

When the packaging tube 10' is twisted and moves axially relative to the end cap 11' and autoinjector (as shown in Figure 9A), the guide ribs 86 are guided up the ramps 88 causing the pin wedge 13 to withdraw from within the flexible fingers 61a (Figure 9B).

Further twisting of the packaging tube 10' relative to the end cap 11' causes the guide ribs 86 to reach the top of the ramps 88 and abut endstops 88a as shown in Figure bA.

At this point the pin wedge 13 is removed clear of the flexible fingers 61a so that the flexible fingers 61a are free to flex radially-inwards allowing reconstitution to begin. The process of reconstitution then occurs as described above, It should be noted that the present embodiment allows reconstitution to be initiated before complete removal of end *** 25 cap 11'. By the time the user has removed the end cap 11' completely from the autoinjector, the reconstitution has occurred. This is important for applications where it S...

might be undesirable for the patient if an injection is administered before reconstitution is * complete. *** * S..

In order for the user to administer an injection of medicament, the end cap 11' must be S...

*..: fully removed from the packaging tube 10'. The end cap 11' is freed from the packaging tube 10' when the guide pin 84 passes through the open end 82a of the channel 82 (Figure 11). Removal of the end cap 11' preferably also removes the end cap and/or needle sheath from the needle so that, with the end cap 11' removed, the front end of the autoinjector 90 is revealed and ready for actuation. Alternatively, the end cap and needle sheath of the autoinjector (not illustrated) could be removed by the user in a separate stage.

In one embodiment, the packaging tube 10' may also be removed from the autoinjector 90 at this stage, the autoinjector being actuated to deliver medicament by the user directly acting on the outer housing of theautoinjector (as described above). However, in the illustrated embodiment, it is not necessary to remove the packaging tube 10' and the autoinjector can be actuated to deliver medicament to an injection site 92 by application of a forward force F (Figure 12) to the packaging tube 10'. In this instance, the packaging tube 10' itself forms part of the injection delivery means of the autoinjector. The force F is transmitted to the autoinjector through the guide ribs 86.

Actuation then occurs according to the process described above with reference to Figures 5-7.

The improved autoinjector described herein is quick and easy to operate by the user and is particularly, but not exclusively, suitable for use in emergency applications. The reconstitution of the medicament has the advantage of comprising effective mixing of the wet and dry components (rather than simply flushing one through the other upon exiting the device) but does not unduly prolong the overall operating time of the device because the mixing is initiated automatically upon opening the outer packaging tube and can take place whilst the user is moving the device to the desired injection site. In addition, the user may wish to reconstitute the medicament but then re-seal the packaging (replace the cap, for example) so that the packaging can be reopened and the already reconstituted medicament delivered quickly as required in an emergency situation. This would only be possible for certain medicaments having suitable storage properties. * S * S..

Alternative types of packaging which are capable of initiating the reconstitution of the :r medicament are envisaged. For example, instead of the outer packaging tube 10 and pin wedge 13, the autoinjector could be wrapped in a sealed flexible plastics material, the opening of which initiates reconstitution of the medicament, perhaps upon release of S...

: a vacuum seal, or by releasing a previously-constrained component.

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Alternative seals between the wet and dry chambers are possible instead of the needle 51 staked in the dry chamber stopper 41. For example, both the rear of the dry chamber and the front of the wet chamber may be sealed with stoppers, septums or the like, and a double-ended needle could be provided therebetween. The double-ended needle could be staked at both ends into the respective stoppers, both being punctured by the needle during the reconstitution stage. Alternatively, the double-ended needle could initially be in contact with neither of the stoppers (a "floating needle") and only contact and then puncture them during the reconstitution stage. One such example of a ufloating needle" 51' is shown in Figure 13 prior to reconstitution. The needle 51' has a rear end 51a' proximate the wet chamber 50 and a front end 51b' proximate the dry chamber 40a and is located in a needle hub, 98. Upon removal of the pin wedge 13, the force of the forward moving reconstitution ram 61 causes forward axial movement of the needle hub 98 and the needle 51' so that the front end 51b' penetrates the dry chamber stopper 41.

Once the front end 51 b' of the needle 51' has entered the dry chamber 40a, the wet chamber 50 continues to move axially forward over the needle 51'. The rear end 51a' of the needle then penetrates a septum 96 in the wet chamber 50 thereby establishing fluid communication between the wet 50 and dry 40a chambers. Reconstitution of the wet and dry components of the medicament can then take place as described above with reference to Figure 4. Other alternatives regarding seals, stoppers and needles will be envisaged by the skilled reader.

The reader'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.

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, **. 25 may be combined in any combination, except combinations where at least some of such features and/or steps are mutually exclusive.

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.

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. * ** * * * * ** **** * I **** III. * **** * S.. S..

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Claims

1. An autoinjector kit comprising an autoinjector including: a first chamber for containing a dry component of a medicament, and a second chamber for containing a wet component of a medicament; reconstitution means for mixing said dry and wet components by placing said first and second chambers into fluid communication with one another, packaging; wherein said packaging is adapted to automatically actuate said reconstitution means to mix said dry and wet components upon movement of at least a part thereof relative to at least a part of the autoinjector.

2. The autoinjector kit of claim 1 wherein at least a part of said packaging comprises a part of an injection delivery means of said autoinjector.

3. The autoinjector kit of claim 1 or claim 2 wherein said opening involves the removal of said autoinjector from said packaging.

4. The autoinjector kit of any of claims 1-3 wherein said packaging includes an inwardly-directed pin or protrusion which is capable of interacting with a component of said autoinjector.

5. The autoinjector of claim 4 wherein said pin or protrusion is integrally -formed with said packaging. * . ****

6. The autoinjector kit of any of the preceding claims wherein said packaging :r includes a main packaging section and a removable front end cap. * 0,*

7. The autoinjector kit of any of the preceding claims wherein said main **** packaging section comprises a generally cylindrical tube.

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8. The autoinjector kit of claim 6, or claim 7 when dependent on claim 6, wherein said end cap includes a guide means capable of cooperating with guide means on said main packaging section to guide relative movement therebetweeri along a defined path.

9 The autoinjector kit of claim 8 wherein said end cap guide means comprises a generally helical channel and said main packaging guide means comprises an inwardly-directed pin or protrusion.

10. The autoinjector kit of any of claims 6-9 wherein said autoinjector is axially fixed with respect to said front end cap.

11. The autoinjector kit of any of claims 6-10 wherein said autoinjector is axially moveable with respect to said main packaging section.

12. The autoinjector kit of any of claims 6-11 wherein said main packaging section includes a guide means capable of cooperating with guide means on said autoinjector to guide relative movement therebetween along a defined path.

13. The autoinjector kit of claim 12 wherein said main packaging guide means comprises at least one inwardly directed rib or protrusion.

14. The autoinjector kit of claim 12 or claim 13 wherein said autoinjector guide means comprises at least one generally helical ramp.

15. The autoinjector kit of any of claims 1 to 5 wherein said packaging includes a sealed flexible wrapping. * ** * * *

*::::*

16. The autoinjector kit of any of the preceding claims wherein said autoinjector is as claimed in any of claims 20-26. *

17. An autoinjector kit substantially as described herein with reference to and as illustrated by any appropriate combination of the accompanying drawings.

* *

18. A method of reconstituting a two-part medicament comprising the steps of: * providing an autoinjector kit as claimed in any of claims 1 to 17; and opening said packaging so as to actuate said reconstitution means.

19. A method of reconstituting a two-part medicament comprising the steps of: providing an autoinjector kit as claimed in any of claims 8 to 14; moving at least part of said packaging relative to at least a part of said autoinjector so as to actuate said reconstitution means; and, preferably, removing said end cap;.

20. An autoinjector including: a first chamber for containing a dry component of a medicament, and a second chamber for containing a wet component of a medicament; an axially-moveable stopper intermediate the first and second chambers; reconstitution means for mixing said dry and wet components by putting said first and second chambers into fluid communication with one another; wherein said reconstitution means is capable of pressunsing said wet component so that, upon entry of the pressurised wet component into said first chamber, hydraulic forces cause said axially-moveable stopper to move so as to increase the volume of said first chamber to accommodate said wet component.

21. The autoinjector of claim 20 further comprising injection delivery means which is separately actuable to said reconstitution means.

22. The autoinjector of claim 20 or claim 21 wherein said stopper abuts said dry component in said first chamber.

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23. The autoinjector of any of claims 20-22 wherein said stopper provides a seal between said first and second chambers. J.

24. The autoinjector of any of claims 20-23 wherein said reconstitution means includes a needle in fluid communication with said second chamber, moveable between a first position in which the needle is staked into said stopper and sealed from said first chamber, and a second position in which * * the needle punctures said stopper so that said first and second chambers are in fluid communication with one another.

25. The autoinjector of any of claims 20-23 wherein the rear of said first chamber and the front of said second chamber are sealed with a stopper, septum or other seal and wherein said reconstitution means includes a needle moveable between a first position in which the needle is floating between said first and second chamber seals, and a second position in which the needle punctures said first and second chamber seals so that said first and second chambers are in fluid communication with one another.

26. An autoinjector substantially as described herein with reference to and as illustrated by any appropriate combination of the accompanying drawings. * .* * * S * SS * S *5S* *S*c.

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