Cross Reference

[0001 ] This application claims priority from Australian Provisional Patent

Application No. 2015902816 filed on 16 July 2015, the contents of which are to be taken as incorporated herein by this reference.

Technical Field

[0002] The present invention relates generally to a spray device and a dosage cartridge. The spray device and dosage cartridge are arranged to be connected together to form an assembled dispensing or delivery device. The invention has particular, but not exclusive, use for delivering opioid medicaments nasally or orally to a patient.

Background of Invention

[0003] Pain relief drugs such as fentanyl can be readily administered nasally. Consequently, in Australia paramedics and ambulance officers have been

administering nasal fentanyl to patients requiring prompt pain relief since about 1990. Nasal delivery is achieved by drawing the required dosage using a syringe from an ampoule or vial, and then squirting the dosage from the syringe by depression of the plunger directly into the nasal cavity of the patient.

[0004] Proper delivery of narcotic drugs such as fentanyl nasally is not without problem for a number of reasons. Firstly, fentanyl is typically available in 100mcg/2ml ampoules. As such, this product is too dilute to deliver the required dosage of up to 200mcg for adults and up to 50mcg for children. This is because with such a commercial product it would be necessary to instil 4ml nasally for adults and 1 ml for children. Given that the nasal cavity can only hold up to 0.2ml volume before run off occurs down the nose or at the back of the throat, delivery of volumes in excess of 0.2ml is ineffective. In an attempt to address this problem, fentanyl has been supplied in a 600mcg/2ml concentrated form in a vial. Again however, a 200mcg dose for adults would require 0.33ml to be instilled to each nostril of the patient resulting in run off and thus incorrect patient dosage. Further, once the 200mcg dosage has been given to the patient from the 2ml vial, more than 1 ml of product remains in the vial which may be diverted for illicit use.

[0005] Another problem with current arrangements for delivering drugs such as fentanyl nasally at an accident scene is that the orientation of the patient may be such that delivery into the nostril is ineffective. For example, if the patient is trapped in an upside down vehicle, proper delivery of the fentanyl into the nasal passages may not be achievable. The fentanyl may simply run out of the patient's nostril before transmucosal uptake or the patient's orientation may not allow administration using a plunger controlled type device.

[0006] Providing fentanyl in vials without tamper evident packaging is also problematic because there have been instances where liquid fentanyl has been drawn off from a vial for illicit use and then the vial returned to capacity by adding water. This is very dangerous because a patient may later receive an inadequate pain relief dosage which may impede their medical care. Further, it may cause confusion by medical personnel because of a patient's response to the alleged pain relief dosage previously received.

[0007] Fentanyl nasal spray is available for the management of breakthrough pain in adult cancer patients who are tolerant to opioid therapy for their underlying persistent cancer pain. However, the use of such sprays is closely controlled and the devices are intended for use by specific patients with known medical history. Such devices are not suitable for use by paramedics or ambulance officers because of the volume remaining in the glass bottle containing the fentanyl after a single patient use. Further, the pump of such sprays is permanently attached to the glass bottle containing the opioid and thus it is not possible to select a pump size as needed for a particular patient.

[0008] Various spray devices are known in the art for spray delivery of

medicaments. For example, US patent 7,296,566 teaches a nasal spray device including a drug container, in the form of a syringe, and a separable spray nozzle. The nozzle includes an internal valve which only allows pressurized liquid to flow through a conduit in the nozzle so that a mist or spray of medicament is released when the plunger is pressed by the user.

[0009] US 2002/0174865 teaches a nasal spray system including a standard syringe, a disposable pre-filled nasal spray tip, and a disposable snap cap for protection of the tip. To dispense medicament, the snap cap is removed and the syringe mated to the nasal spray tip. Upon insertion into a nasal passage, the syringe plunger is pushed into the syringe forcing atomized fluid to be dispensed into the nasal passage.

[0010] Both US patent 7,296,566 and US 2002/0174865 make use of

conventional syringes and plungers to dispense the medicament. Both leave substantial residual medicament in the syringe and nozzle/tip after a treatment regime which may be diverted for illicit use. Further, the volume of medicament dispensed to each nostril is not well controlled because of varying depression forces applied by different users, leading to possible over or under dosing. Varying depression forces also effect whether the medicament is dispensed as a stream or as a spray. Also, as mentioned previously, the use of a plunger type delivery system is typically

problematic when the patient's orientation is other than sitting or when access to the patient is restricted.

[001 1 ] EP 201 1467 describes a fluid container and an airless fluid dispensing system that does not rely on a plunger type delivery system. The fluid container holds a gel liquid which is sucked out of the container and dispensed via the spout when a pump is actuated. However, before the liquid can be dispensed, the device must be primed to remove air from within the container space and from within the pump itself. This requires the user to depress the pump a number of times so as to evacuate all air from within the pump and the container. It is only after that action occurs and thus the device is primed, that fluid can be dispensed. If air remains trapped within the container body, which is a common problem, it may not be possible to dispense any fluid to the patient, or if fluid is dispensed, the volume of fluid dispensed cannot be guaranteed. This may lead to over or under dosing of the patient which can be problematic as explained previously. [0012] Accordingly, there is a need to provide a delivery device that can reliably deliver the required patient dosage of a medicament. Preferably, such a delivery device is also configured to provide evidence of any prior tampering with the medicament. Advantageously, such a delivery device is also preferably configured or useable such that only a minimal amount of any medicament is retained in the device after normal use and/or which device can be locked to prevent later use or extraction of any remaining medicament.

[0013] The present invention seeks in one aspect to provide an improved a delivery device. In a further aspect, the invention seeks to provide an improved tamper evident dosage cartridge for housing a medicament vial. The various aspects of the invention may address one or more of the deficiencies of the prior art mentioned above.

[0014] The discussion of the background to the invention herein is included to explain the context of the invention. This is not to be taken as an admission that any of the material referred to was published, known or part of the common general knowledge as at the priority date of this application.

Summary of Invention

[0015] According to one aspect of the present invention there is provided a delivery device for spraying a medicament product as a series of sprays, the delivery device including: a spray device and a cartridge; the spray device including a pump; the cartridge including a vial and a plunger, the vial bounding in part a chamber in which is located a piston, the piston dividing the chamber of the vial into a first part in which a medicament product is located and a second part which is open to atmosphere; wherein when the spray device is connected to the vial a dosage flow path is established between the first part of the chamber and an outlet of the pump; and wherein at least an upper part of the plunger is arranged to be received in the vial and the plunger is operable by a user so that actuation of the plunger primes the pump by forcing air within the dosage flow path out of the outlet, that air being replaced with medicament product from the first part of the chamber, and so that thereafter, when the pump is operated, the piston is drawn along the chamber forcing medicament product to move along the dosage flow path and out of the outlet of the pump.

[0016] Preferably, operation of the plunger to prime the delivery device involves pressing the plunger into the vial until it reaches a stop position. In this stop position of the plunger, all of the air within the dosage flow path prior to priming will be replaced with medicament product.

[0017] The spray device preferably further includes connector with a lower end arranged for screw connection, luer lock connection, or a luer slip connection to an upper opening of the vial.

[0018] The connector preferably includes an upper end arranged for connection to the pump. The connector is preferably connected to a dip tube of the pump.

[0019] The connector and/or pump may be colour coded or otherwise marked to distinguish between different dosage capabilities of the pump. For example, one colour (e.g. red) may be used to indicate that the spray device is suitable for adult patients, whilst another colour (e.g. blue) may be used to indicate that the spray device is suitable for child patients.

[0020] The delivery device is arranged to enable a series of sprays of product from the vial to be discharged. Once the sprays of product have been discharged as part of a treatment episode with a particular patient, the delivery device is arranged to be disposed of. If further product is required to be administered to the patient and the vial contains no further sprays, the cartridge can be disconnected from the connector and a fresh cartridge attached to the spray device.

[0021 ] The vial preferably includes a body having an upper opening, a lower opening, and the chamber is defined at least in part therebetween. The body may be made of glass or plastic or any other suitable material. [0022] The cartridge further includes a cap or other device for covering the lower opening of the vial. The cap is configured to keep the second part of the chamber exposed to atmosphere.

[0023] The piston is movable along an inner wall of the chamber and seals against the inner wall to prevent medicament product from being discharged from the first part of the chamber into the second part of the chamber.

[0024] The pump is preferably configured to dispense the product via the outlet in a mist or spray, and preferably under pressure.

[0025] The spray device may further include an outer housing that includes a gripping surface configured to enable a user to operate the delivery device without placing their fingers too close to the patient's nostrils or mouth. The user's fingers are preferably spaced from the patient's nostrils and/or mouth. The gripping surface may include one or more flanges, each establishing a surface for the user to engage the delivery device so that it can be held between thumb and at least one finger, with said at least one finger located against the flange.

[0026] The upper opening of the vial preferably includes a screw threaded connector, luer lock connector, or a luer slip connector arranged for connection to the lower end of the connector.

[0027] In accordance with a preferred embodiment, the cartridge is supplied separately to the spray device. The cartridge is preferably supplied in a tamper evident package or is formed in a manner to be tamper evident.

[0028] In accordance with one embodiment of the invention, the cartridge is a tamper evident cartridge. The tamper evident cartridge includes a vial holder with a least one internal cavity for holding the vial. The vial holder may be made from multiple parts, typically only two parts, that are locked together so as to define the at least one internal cavity for holding the vial. The parts of the vial holder are locked together so as to prevent unintentional separation and preferably also so that if the parts are later intentionally unlocked from one another, such previous unlocking will be detectable by a user so that they are alerted to possible tampering of the vial contained within the vial holder. [0029] When the multiple parts are locked together to form the vial holder they establish an upper section of the vial holder, a mid-section of the vial holder and a lower section of the vial holder. Each of the upper, mid and lower sections of the vial holder includes a portion containing multiple parts.

[0030] The vial holder further includes a first zone of weakness configured to enable the upper section of the vial holder to be broken away from the mid-section of the vial holder to enable access to a part of the vial. Removal of the upper section of the vial holder provides user access to an upper opening of the vial.

[0031 ] The vial holder preferably further includes a second zone of weakness configured to enable a lower section of the vial holder to be readily removed from the mid-section of the vial holder. Removal of the lower section of the vial holder provides access to a plunger. The plunger is arranged so that when activated by a user it moves the piston contained within the vial to a position in which the delivery device is primed ready for use (i.e. the first pump of the spray device will result in a spray of medicament being released to the patient).

[0032] The first and second zones of weakness preferably extend in a plane substantially perpendicular to the plane of a join line between the first and second parts of the vial holder.

[0033] The cartridge preferably includes at least one barrier, for example at least one metal disc, located within the cartridge so as to prevent a needle or the like from being passed through either of the parts forming the vial holder to gain access to the contents of the vial.

[0034] According to another aspect of the invention there is provided a spray spray device for spraying a medicament product as a series of sprays, the spray device including a pump and a connector for connecting the pump to a disposable dosage cartridge containing the medicament product so that a dosage flow path is established through the connector and between a first part of a chamber of the dosage cartridge and an outlet of the pump, the first part of the chamber being defined at least in part by a piston located within the chamber, the piston being configured for movement within the chamber when the pump is operated, and wherein the dosage cartridge and pump are selected so that following a predetermined dosage regime only minimal medicament product is retained in the spray device.

[0035] The term "minimal medicament product" as used herein should be understood to refer to an amount of medicament product that if later used illicitly would represent little or no risk to the illicit user.

Brief Description of Drawings

[0036] Embodiments of the invention will now be described, by way of example only, with reference to the accompanying drawings in which:

[0037] Figure 1 is an assembly view of the components of a delivery device in accordance with an embodiment of one aspect of the invention;

[0038] Figure 2 illustrates the vial of the delivery device shown in Figure 1 being fitted with a cap and a floating piston;

[0039] Figure 3 illustrates the vial of the delivery device shown in Figure 1 with the floating piston located within the chamber;

[0040] Figure 4 indicates the general assembly process of the components of the delivery device shown in Figure 1 ;

[0041 ] Figure 5 illustrates the assembled delivery device;

[0042] Figure 6 is an assembly view of a delivery device according to an embodiment of another aspect of the invention with the upper and lower sections of the tamper evident cartridge removed;

[0043] Figure 7 is a view of the assembled delivery device of Figure 6;

[0044] Figure 8 is a cross-sectional view along line A-A of Figure 7;

[0045] Figure 9 is a cross-sectional view of the connector shown in Figure 6;

[0046] Figures 10A to 10C are respective isometric, top and cross-sectional views of the outer housing of the spray device shown in Figure 6; [0047] Figures 1 1 A to 1 1 D are respective first isometric, second isometric, front and side views of the male half of the vial holder of a delivery device according to the embodiment of the invention;

[0048] Figures 12A to 12D are respective first isometric, second isometric, front and side views of the female half of the vial holder of a delivery device according to the embodiment of the invention;

[0049] Figure 13 is an assembly view of a tamper evident cartridge in accordance with an embodiment of the invention; and

[0050] Figures 14A and 14B are respective front and cross-sectional views of the assembled tamper evident cartridge of Figure 13.

Detailed Description

[0051 ] Figure 1 illustrates an assembly view of the components of a delivery device 5 in accordance with an embodiment of one aspect of the invention. The delivery device 5 includes a spray device 10 and a dosage cartridge 100. The following description is generally made with reference to a delivery device 5 suitable for nasal delivery of a medicament. However, it should be appreciated that the delivery device need not be so limited and that the device may deliver a medicament orally or by way of oromucosal delivery.

[0052] The spray device 10 shown in Figure 1 to 5 includes a pump 12 and a connector 14 for connecting the pump 12 to the dosage cartridge 100. The spray device 10 also includes a flange extender 16.

[0053] The pump 12 may be a standard metered-dose mechanical pump

(otherwise known as a nasal inhaler actuator) commercially available for nasal spray or oral spray delivery of a medical product. These are well known in the art and thus a detailed description of the pump 12 and its mode of operation will not be provided. The pump 12 may include an optional dust cap (not shown).

[0054] The connector 14 may be permanently secured to a dip tube 12a of the pump 12 or may be removably attachable thereto. As illustrated in Figures 1 to 6, the connector 14 is arranged for a press or sliding type fit to the dip tube 12a. [0055] The dosage cartridge 100 includes a body in the form of a vial 102. The vial 102 has an upper opening 104 and a lower opening 106. A flange 108 extends about the lower opening 106. A chamber 1 10 is defined at least in part between the upper opening 104 and the lower opening 106. The body 102 may for example be a glass or plastic vial. It is intended that the dosage cartridge 100 is disposable.

[0056] The dosage cartridge 100 further includes a cap 1 12 (referred to hereafter as the thumb cap 1 12) for covering the lower opening 106 of the vial 102 and a removable top cap 1 14 for sealing the upper opening 104 of the vial 102. As best shown in Figures 3 and 5, a piston 1 16 is located within the chamber 1 10 so that a medicament product can be located within a first part A of the chamber 1 10 bounded at least in part by the upper opening 104 and the piston 1 16. A second part B of the chamber 1 10 is bounded at least in part by the piston 1 16 and the thumb cap 1 12. It will thus be appreciated that the volume of the first part A of the chamber 1 10 and the volume of the second part B of the chamber 1 10 will vary as the piston 1 16 is drawn along the chamber 1 10.

[0057] Piston 1 16 is arranged to be movable along an inner wall of the chamber 1 10 and seals against the inner wall to prevent product from being discharged from the first part of the chamber A into the second part B of the chamber. The piston 1 16 is arranged to be drawn along the inner wall of the chamber 1 10 towards the upper opening 104 when the pump 12 is pumped by the user.

[0058] Figure 2 illustrates fitting of the removable cap 1 14 to the upper opening 104 of the vial 102, and fitting of the piston 1 16 into the chamber 1 10 via the lower opening 106. Figure 3 shows the piston 1 16 within the chamber 1 10 of the vial 102. A medicament product, for example fentanyl, is loaded into the vial 102 and is contained within the first part A of the chamber 1 10. The medicament product is held during storage of the dosage cartridge 100 within the first part A of the chamber 1 10 between the piston 1 16 and the cap 1 14 located within the upper opening 104 of the vial 102.

[0059] Figure 4 shows the dosage cartridge 100 with cap 1 14 removed and connector 14 being installed. The twisted arrow in Figure 5 is representative of a twist type connection between the lower end 14a of the connector 14 and the upper opening 104 of the dosage cartridge 100. It will be appreciated that various different connection mechanisms can be used.

[0060] The connector 14 includes a body with a dosage channel 14b extending there through. When the connector 14 is connected between the pump 12 and the dosage cartridge 100, a dosage flow path is established between the first part A of the chamber 1 10 of the dosage cartridge 100 and the outlet 12c of the pump 12. The outlet 12c is typically formed at the top most part of the nose piece 12b of the pump 12. The dosage flow path extends through the dip tube 12a of the pump 12.

[0061 ] The connection between the connector 14 and vial 102 is preferably via a screw type connection, luer lock connection, or a luer slip connection. The

connection should be one that can be easily and quickly made and thus it is preferred that a connection arrangement of a type appearing on commonly used medical devices be adopted.

[0062] The flange extender 16 is arranged to snap fit over the pump 12. The flange extender 16 includes a body with a centrally located aperture 16a shaped and sized so that the nose piece 12b of the pump 12 can extend there through when the flange extender 16 is located on the pump 12. Flanges 16b extend either side of the body and establish surfaces for a user to engage the spray device 10. Accordingly, when the spray device 10 is connected to a dosage cartridge 100, the assembled delivery device 5 can be held by the user between thumb and at least one finger of the same hand, with the at least one finger located against the top surface of one of the flanges 16b. Typically, the user would use two fingers, with one finger pressed against each flange 16b (i.e. one either side of the nose piece 12b). In this way, the user's fingers are able to generally avoid contact with the patient's nostrils. The user's thumb would rest against the thumb cap 1 12.

[0063] The thumb cap 1 12 is arranged to clip over the flange 108 of the lower opening 106 of the vial 102. To this end, the thumb cap 1 12 includes at least two fingers that engage over the flange 108 to hold the thumb cap 1 12 to the vial 102. The connection is preferably a snap type fit. [0064] The lower face of the thumb cap 1 12 provides an engagement surface for the user's thumb when holding the delivery device 5 ready for use. The lower face is preferably planar.

[0065] Although the thumb cap 1 12 covers the lower opening 106 of the body 102, and thereby provides a surface against which a user's thumb can be placed during use of the delivery device 5, the thumb cap 1 12 is arranged so as to not seal off the lower opening 106 from atmosphere. To this end, in accordance with one

embodiment, the thumb cap 1 12 includes a longitudinal groove extending

diametrically across its upper face and a pair of openings. The groove and the openings are arranged to allow air to enter the lower part B of the chamber 1 10 when the delivery device 5 is in use. Accordingly, when the delivery device 5 is being primed or is pumped to provide a spray of product, piston 1 16 is able to be drawn along the chamber 1 10 towards the upper opening 104. The groove and the openings prevent a vacuum from forming in the lower part B of the chamber 1 10 which would otherwise restrict movement of the piston 1 16 or cause it to be sucked back along the chamber towards the thumb cap 1 12.

[0066] It is envisaged that the spray device 10 may be provided in a non- sterile package. The dosage cartridge 100 is preferably provided in a tamper evident package. For example, the tamper evident package may include a container with a screw top. Shrink wrap is preferably applied to the container and screw top so that prior removal of the screw top will be evident by damage to the shrink wrap.

Alternatively, the tamper evident package may include a container with a tamper evident seal as commonly used for other medicaments.

[0067] When a decision is made by a user, for example a paramedic, to

administer a medicament such as fentanyl nasally using a delivery device 5 according to an embodiment of the invention, the user must first select the appropriate nasal spray device 10 for the patient and also select the drug to be administered. For the purpose of this description, the drug will be fentanyl and the dosage cartridge 100 will contain 1 ml of 250mcg/ml fentanyl nasal solution. The dosage cartridge 100 is for single patient use and is intended to be disposable. [0068] The user selects the appropriate spray device 10 taking into consideration both the medicament to be administered and the particular patient, and removes it from its packaging. The user then breaks the seal on the tamper evident package containing the dosage cartridge 100. This is typically done by simply twisting the screw top off the container.

[0069] Once the user has selected the appropriate spray device 10 and has a dosage cartridge 100 in hand, the removable cap 1 14 is removed from the vial 102 of the dosage cartridge 100 and the lower end of the connector 14 of the selected spray device 10 is connected to the upper opening 104 of the vial 102. A flange extender 16 is connected to the pump 12 of the spray device 10 if the pump 12 does not otherwise include a flange extender 16 or other similar component. The assembled delivery device 5 is then ready for priming in anticipation of use.

[0070] Priming is achieved by pumping the delivery device 5 so as to pump air out of the dosage flow path established through the connector 14 and between the first part A of the chamber 1 10 of the vial 102 and the spray outlet 12c of the pump 12. As the air is pumped out of the dosage flow path, it is replaced by fentanyl solution from the vial 102. As this occurs, the piston 1 16 located within the chamber 1 10 of the vial 102 is drawn towards the upper opening 104 reducing the volume of the first part A of the chamber 1 10 and increasing the volume of the second part B of the chamber 1 10. The next pump of the delivery device 5 will result in a spray of fentanyl solution being forced out of the outlet 12c in the nose piece 12b of the pump 12. The piston 1 16 will again be drawn towards the upper opening 104 so that the expelled fentanyl solution is replaced within the dosage flow path by fentanyl solution previously contained in the first part A of the chamber 1 10.

[0071 ] If the patient is an adult, the user will select an adult spray device 10 which will preferably be clearly identifiable to the user by labelling and/or colour coding. For example, a red colouring on the spray device 10 may be used to indicate that the spray device 10 is suitable for adult use and will thus operate to dispense 50mcg per spray. Four such sprays, two 0.2ml sprays to each nostril, would deliver the recommended adult dosage of fentanyl. If all four dosages are not given to the patient, the user should expel the remaining dosages to the atmosphere, well away from the patient, themselves, or any bystanders. [0072] If the patient is a child or a particularly frail person, the user will select a child spray device 10 which will preferably be clearly identifiable to the user by labelling and/or colour coding. For example, a blue colouring on the spray device 10 may be used to indicate that the spray device 10 is suitable for child/frail use and will thus operate to dispense 25mcg per spray. Four such sprays, two 0.1 ml sprays to each nostril, would deliver the recommended child dosage of fentanyl. One dosage cartridge 100 would hold enough fentanyl for eight child/frail dosages. If all eight dosages are not given to the patient, the user should expel the remaining dosages to the atmosphere, well away from the patient, themselves, or any bystanders.

[0073] When all of the dosages have been expelled from the delivery device 5, the residual volume of fentanyl solution left will be no more than about 0.05ml. Such a small residual volume is considered to be minimal and of little concern. Even if the delivery device 5 is accidentally left at an incident site, rather than being properly disposed of by the user, there is no substantive risk that the residual volume at such a minimal level could be removed from the delivery device 5 or a discarded dosage cartridge. Even if the residual volume was removed, it is so minimal that it does not represent a risk in the event of illicit use.

[0074] A particular advantage of embodiments of the present invention is the ability of the delivery device to be used in a variety of different orientations, even upside down. This is possible because of the internal pressure developed during priming and subsequent pumping of the delivery device which ensures that the dosage flow path remains full with medicament during a dosage regime Accordingly, a full dosage of medicament is always provided per pump.

[0075] It will be appreciated that by careful selection of both the spray device and dosage cartridge (including the volume and concentration of the product contained therein) it is possible to ensure that only minimal product is retained in the delivery device 5 after a recommended dosage of the product is given to the patient in a series of sprays (i.e. pumps of the device). If less than the recommended dosage is given to the patient or if for other reasons a number of sprays are left in the delivery device, the user can quickly dispose of those sprays (i.e. any unused medicament product) by pumping the delivery device dispersing any remaining medicament product in the vial out to atmosphere. This will only take a few seconds and results in only minimal product being retained in the vial of the delivery device.

[0076] As the dosage cartridge 100 according to the first embodiment of the invention is intended to be supplied in a tamper evident package and is designed for single patient use only, a user will be aware that a patient should only be treated with product that has just been removed from such a tamper evident package. If there is any indication that the tamper evident package has been opened or an opening attempt has previously occurred, the dosage cartridge should not be used and should be properly disposed of. Accordingly, on no occasion should there be any risk of a patient not being administered the required medicament due to illicit substitution of the medicament.

[0077] Figures 6 to 14B illustrate components of a delivery device 200 according to a second embodiment of the invention. Figure 6 illustrates the delivery device 200 as it would appear just prior to one mode of use of the delivery device 200. The delivery device 200 includes a spray device 210 and a tamper evident cartridge 300. The tamper evident cartridge 300 includes a vial holder 400, a medicament vial 500, and a plunger 600. It is important to note that Figures 6 to 8 illustrate the tamper evident cartridge 300 following removal of an upper section U and a lower section L of the vial holder 400, so that only the mid-section M is retained (compare Figure 7 with Figure 14A). The removal of the upper and lower sections U, L of the vial holder 400 will be discussed in more detail below. The plunger 512 is not illustrated in Figure 6, but would be located within the vial 500 along with the medicament.

[0078] The spray device 210 includes a pump 212, a connector 214 and an outer housing 216. The pump 212 may be a standard metered-dose mechanical pump (otherwise known as a nasal inhaler actuator) commercially available for nasal spray or oral spray delivery of a medical product. These are well known in the art and thus a detailed description of the pump 212 and its mode of operation will not be provided.

[0079] As shown in Figure 9, the connector 214 is generally funnel shaped and has a lower end 214a and an upper end 214b. The upper end 214b of the connector 214 is arranged to be attached to the dip tube 212a of the pump 212. The attachment is preferably achieved by a press or sliding type fit. As will be explained in detail below, the lower end 214a of the connector 214 is arranged to connect with the upper end of the vial 500.

[0080] Figures 10A to 10C better illustrate the outer housing 216 of the spray device 210. As shown, the outer housing 216 is generally tubular and has an upper aperture 216a shaped and sized so that the nose piece 212b of the pump 212 can extend there through when the outer housing 216 is located on the pump 212.

Flanges 216b extend from either side of the outer housing 216 to establish user engagement surfaces. As will be explained below, the outer housing 216 is arranged to connect with the exterior of the vial holder 400.

[0081 ] Two open ended elongate slots 218 extend from the lower edge 216c of the outer housing 216 and toward the upper end thereof. The slots 218 are diametrically opposed to one another as shown in Figure 10B. A locking channel 220 is also formed on the inner face of the outer housing 216 adjacent the lower edge 216c. The locking channel 220 extends circumferentially about part of the inner face of the housing 216. The function of the respective slots 218 and locking channel 220 will be detailed later.

[0082] As best shown in Figures 13, 14A and 14B, the tamper evident cartridge 300 includes both the vial holder 400 and the medicament vial 500. The vial holder 400 is formed from male and female halves 410, 420 which fit together, preferably with a snap type fit, to establish the vial holder 400 in which the vial 500 is securely located.

[0083] Figures 1 1 A to1 1 D show the male half 410 of the vial holder 400. The male half 410 includes a circular base 412, a plunger half cavity 414 located between the base 412 and an upper part wall 413, a vial half cavity 416, and cap half cavity 418. Each of the "male" half cavities are configured to mate with the respective half cavity of the female half 420 of the vial holder 400 to establish full cavities to receive respectively the plunger 600, the vial 500, and the upper part of the vial 500 with cap 502 fitted thereto.

[0084] Figures 12A to 12D show the female half 420 of the vial holder 400. The female half 420 includes a circular top 422, a plunger half cavity 424, a vial half cavity 426, and a cap half cavity 428. Female half 420 also includes an opening that establishes a viewing window 420d through which the vial 500 can be sighted. The viewing window 420d enables a user to monitor the contents of the vial 500 and movement of the piston 512 and plunger 600.

[0085] It will be noted that both the male half 410 and female half 420 of the vial holder are moulded from a plastics material. To reduce cooling time during the moulding process and to minimise material costs, each half 410, 420 includes a series of cut outs 410c, 420c which reduce the volume of the half 410, 420.

[0086] The snap fit connection between the male and female halves 410, 420 of the vial holder 400 is achieved by the engagement of respective male and female parts 410a, 420a. As shown in Figures 1 1 A to 1 1 D, the male half 410 of the vial holder 400 includes three male parts 410a spaced along each side of its length (i.e. six male parts 410a). These male parts 410a are arranged to be located within associated female parts 420a formed on the female half 420 of the vial holder 400. When each male part 410a is located within the associated female part 420a, a male locking lip 420b on the female part 420a is received within a groove 410b formed on the associated male part 410a. The locking lip 420b engages within the groove 410b preventing later separation of the male and female halves 410, 420 of the vial holder 400. Although it may be possible to disengage the male and female halves 410, 420 from one another, this will not be achievable without significant effort and is likely to cause visible damage to the vial holder 400. Accordingly, any tampering with the vial holder 400 to try to gain access to the vial 500 should be readily apparent to a later user.

[0087] Figure 13 illustrates an assembly view of the vial cartridge 300. As explained above, the vial cartridge 300 includes both the vial holder 400 and the vial 500 located therewithin. Figure 13 also illustrates the plunger 600. However, the piston 512 is not illustrated.

[0088] Figure 14A illustrates the assembled vial cartridge 300, whilst the cross- sectional view of the vial cartridge 300 shown in Figure 14B clearly shows the vial 500 located within the vial holder 400.

[0089] As best depicted in Figure 14A, the male parts 410a of the male half 410 of the vial holder 400 are sized so that when they engage over the associated female parts 420a, the external diameter of the vial holder 400 remains substantially consistent in the area immediately adjacent to the connection.

[0090] Each of the male and female halves 410, 420 of the vial holder 400 include upper and lower closed ended elongate openings 430, 432. Each of the openings 430, 432 extends circumferentially about their respective male and female halves 410, 420 of the vial holder 400. As best shown in Figures 1 1 D and 12D, a small thickness of material 430a retains the uppermost section U of the vial holder 400 to the mid-section M thereof. Similarly, a small thickness of material 432a retains the lowermost section L of the vial holder to the mid-section M thereof. When the male and female halves 410, 420 of the vial holder 400 are connected together, the small thicknesses of material 430a of the upper grooves 430 in each of the male and female halves 410, 420 abut. Similarly, the small thicknesses of material 432a of the lower grooves 432 in each of the male and female halves 410, 420 abut. Accordingly, two zones of weakness (upper and lower) corresponding to the positioning of the upper and lower closed ended grooves 430, 432 are formed in the vial holder 400.

[0091 ] The two zones of weakness in the vial holder 400 are such that the lowermost section L can be snapped or twisted off from the mid-section M of the vial holder 400 enabling access to the plunger 600 Similarly, the uppermost section U can be snapped or twisted off from the mid-section M of the vial holder 400 enabling access to remove a cap 509 from an upper opening 504 of the vial 500. It is envisaged that the zones of weakness would be configured so that removal of the lowermost section L and/or uppermost section U could be achieved by intentional twisting of the respective sections by the user whilst holding securely to the midsection M.

[0092] It will be noted that the male and female parts 410a, 420a of the male and female halves 410, 420 are positioned so that mating male and female parts 410a, 420a are located in each of the upper section U, mid-section M, and lower section L. This ensures the integrity of the vial holder 400 when either or both of the upper and lower sections U, L are snapped from the mid-section M of the vial holder 400.

[0093] Located on the outer face of each of the male and female halves 410, 420 of the vial holder 400, in the area of the mid-section M of the assembled vial holder 400, is a lug 450. The lugs 450 are arranged to be located within the slots 218 of the outer housing 216 and to guide sliding movement of the outer housing 216 vertically along the length of the vial holder 400 when the delivery device 200 is being pumped for priming or dispensing. The lugs 450 also have a further function in that they can be used in conjunction with the locking channel 220 of the outer housing 216 to prevent any pumping action of the delivery device 200. This is achieved by twisting the outer housing 216 relative to the vial holder 400 until the lugs 450 engage within the locking channel 220. Once the lugs 450 locate within the locking channel 220 and before they drop into a locking socket 220a in the end of the locking channel 220, it remains possible to reverse the twisting movement of the outer housing 216 relative to the vial holder 400 so that the lugs return into the slots 218 and thus pumping action of the delivery device 200 is possible. However, if the outer housing 216 is twisted relative to the vial holder 400 into a position in which the lugs 450 drop into the locking socket or otherwise engage with a portion of the locking channel 220, the outer housing if fixed in a locked position. In this locked position, the lugs 450 are locked within the locking channel 220 of the outer housing 216 and cannot be relocated back to within the slots 218. When so locked, the outer housing 216 is no longer able to move vertically relative to the vial holder 400 and thus pumping of the delivery device 200 can no longer occur.

[0094] The vial 500 is formed as a generally tubular member. The vial 500 has a luer type cap receiving fitting 502 connected to the upper opening 504 and an open lower opening 506. The fitting 502 has a push type fit with the vial 500 and has an internal thread. The internal thread of the fitting 502 facilitates engagement with a vial cap 509 to seal the upper opening 504. Also, when the cap 509 is later removed, the threaded connection helps secure the engagement between the connector 214 and the fitting 502. A flange 508 extends about the lower opening 506 of the vial 500.

[0095] Cap 509 is arranged to be fitted to the cap fitting 502 to close off the upper opening 504. A chamber 510 is defined at least in part between the upper opening 504 and the lower opening 506. A piston 512 is arranged to be located within the chamber 510. When the piston 512 is located within the chamber 510 it divides the chamber into a first part A and a second part B. The first part A is bounded generally by the upper opening 504 and the piston 512. The second part B is bounded generally by the piston 512 and the lower opening 506. As the piston 512 is moved towards or away from the upper opening 504 by virtue of contact with a piston 600, the volume of the first part A and the second part B will vary. In use, medicament is initially provided in the first part A of the chamber 510 and the cap 509 applied.

[0096] As best shown in Figures 13 and 14B, plunger 600 includes an upper part or head 600a, a rod 600b and a disc 600c. The disc 600c provides a pressing surface for driving the plunger 600 into the chamber 510 of the vial 500 during priming of the device 200. In use, the plunger 600 must be pressed into and driven along the chamber 510 by the user so that the upper part or head 600a of the plunger 600 makes contact with the piston 512 and thus moves the piston 512 towards the upper opening 504 of the vial 500. As illustrated, the head 600a, rod 600b and disc 600c are formed as a single unit. However, it is envisaged that a two piece construction may be adopted with the rod 600b being connected to an upper face of the disc 600c.

[0097] Figures 1 1 B and 12B show a semi-circular cut-out 413a formed in each of the part walls 413. When the male and female halves 410, 420 of the vial holder 400 are brought together, the two semi-circular cut-outs form a circular aperture for receiving the rod 600b of the plunger 600. This facilitates proper location of the plunger 600 as orientation of the rod 600b as the plunger 600 is pushed into chamber 510 during priming of the device 200.

[0098] It will be noted from Figure 14b that a metal disc 470 is located in the cap cavity 420 and above the cap 509. The metal disc 470 is provided to prevent a needle being forced through the circular top 422 of the female half 410 of the vial holder 400 to gain access via the cap 509 to the medicament contained in the vial 500. A further metal disc (not shown) may be located in the plunger cavity 414 below the plunger 600 to prevent needle entry to gain access to the medicament. However, it is envisaged that the plunger 600 of itself would normally provide a sufficient bar to entry of a needle in most circumstances.

[0099] As described in relation to the first embodiment, when a decision is made by a user, for example a paramedic, to administer a medicament such as fentanyl nasally using a delivery device 200 according to the second embodiment of the invention, the user must first select the appropriate nasal spray device 210 for the patient and also select the drug to be administered. For the purpose of this description, the drug will be fentanyl and the vial 500 will contain 1 ml of 250mcg/ml fentanyl nasal solution.

[0100] The user selects the appropriate spray device 210 taking into consideration both the medicament to be administered and the particular patient, and removes it from its packaging. The user then selects a tamper evident cartridge 300 which contains a vial 500 of the required medicament and confirms that there is no evidence that the cartridge 300 has previously been tampered with. Once so satisfied, the uppermost section U of the tamper evident cartridge 300 is then twisted off the midsection M so that cap 509 can be removed from the cap fitting 502 and the spray device 210 connected thereto. This is achieved by locating and screwing the free end of the connector 214 into the cap fitting 502. In order for this occur, the lugs 450 must be aligned with their respective slots 218 in the outer housing 216.

[0101 ] The lowermost section L of the tamper evident cartridge 300 is then twisted off the mid-section M so that the lower end (i.e. the disc 600c) of the plunger 600 is exposed. The disc 600c of the plunger 600 is then pressed fully inwardly to the position shown in Figure 8. In this stop position of the plunger 300, the upper face of the disc 600c is in contact with the underside of the circular base 412. This action of pressing the plunger 600 causes the air in the dosage flow path above the piston 512 to be expelled as the piston 512 moves towards the upper opening 504 of the vial 500. That air is replaced with medicament (e.g. fentanyl solution) from chamber A. The delivery device 200 is now primed and is ready for use.

[0102] As the delivery device 200 is now primed, the first pump of the delivery device 200 will then result in a spray of fentanyl solution being forced out of the outlet in the nose piece 212b of the pump 212. The piston 512 will be drawn towards the upper opening 504 under suction so that the expelled fentanyl solution is replaced within the dosage flow path by fentanyl solution previously contained in the first part A of the chamber 510.

[0103] If the patient is an adult, the user will select an adult spray device 210 which will preferably be clearly identifiable to the user by labelling and/or colour coding. Four such sprays, two 0.2ml sprays to each nostril, would deliver the recommended adult dosage of fentanyl. If all four dosages are not given to the patient, the user should expel the remaining dosages to the atmosphere, well away from the patient, themselves, or any bystanders. Alternatively, the user may simply lock the delivery device 200 by twisting the outer housing 216 until the lugs 450 engage and then lock in the locking channel 220. Once the outer housing 216 is twisted to the locked position, further pumping of the outer housing 216 relative to the tamper evident cartridge 300 is prevented.

[0104] As delivery devices according to embodiments of the invention are intended to be clearly labelled or colour coded to identify their suitability for use with an adult or child/frail patient, it will be easier for the user to quickly select and administer the correct dosage of medicament. This will enable the user to quickly provide pain relief to the patient in a manner that is effective irrespective of the orientation of the patient.

[0105] In a non-emergency situation, for example for at home delivery of a medicament, it may be advisable not to prime the delivery device using the plunger 600. In such a situation, and thus in a second mode of use, the lowermost section L of the tamper evident cartridge 300 would not be removed and priming of the delivery device 200 would occur through repeated pumping of the outer housing 216 relative to the mid-section M of the tamper evident cartridge 300. The need to prime the delivery device 200 by repeated pumping may provide a safety feature in the event that a child accidentally gained access to the delivery device 200.

[0106] It should also be recognised that the tamper evident cartridge 300 provides a tamper resistant package for storing vials of a medicament. Accordingly, following removal of the uppermost section U of the vial holder 400 and removal of the cap 509 from the vial 500, a syringe could be used to extract medicament from the vial 500 in a conventional manner.

[0107] In a further non-illustrated embodiment, it is envisaged that the tamper evident cartridge 300 may be modified to remove the lowermost section L of the vial holder and simply replace it with a solid closed end. The resultant tamper evident cartridge would then only have a single zone of weakness. Removal of the uppermost section L of the vial holder would occur by twisting at the zone of weakness to allow access to the top of the vial contained within the tamper evident cartridge. The vial contained in such a modified vial holder could be a standard drug vial with a rubber top. This would allow needle access to the medicament through the rubber top of the vial.

[0108] Delivery devices according to embodiments of the invention when used for nasal delivery of a medicament ensure that the medicament is delivered in a volume that can be held by the patient's nasal cavity and also as a spray rather than as a liquid stream. Delivery can be achieved quickly by the user despite the orientation of the patient because of the pressure established within the chamber of the vial once priming has occurred.

[0109] It is envisaged that the medicament product used in embodiments of the invention could include, for example, ketamine, naloxone, scopolamine, and sedatives etc. Any product that could be administered nasally or orally could be used with a spray device and/or tamper evident cartridge in accordance with an embodiment of the invention.

[01 10] Embodiments of the invention offer differing advantages. Such advantages may for example include:

• Provision of medicaments, which are typically controlled drugs, in a prefilled tamper evident cartridge with a dosage suitable for a single patient treatment;

• Provision of a medicament cartridge that only allows minimal or nil medicament to remain therein after a treatment episode, thereby minimising the risk of any remaining medicament being diverted for illicit use;

• Provision of a medicament cartridge that can be quickly connected to a

delivery device such as a nasal pump; and

• Provision of a medicament cartridge that once connected to a delivery device can be quickly primed ready for use.

The embodiments have been described by way of example only and modifications within the spirit and scope of the invention are envisaged.