Dosage Device with Dispenser and Cartridge Field of the Invention

[0001 ] The present invention relates generally to a device for administering a dose of liquid medicament, therapeutic or other fluid. The dosage device is of the type with a dispenser used with cartridges which may be replaceable, or alternatively the entire device is a ‘single use’ device that is discarded once the cartridge is empty. In particular, the dosage device is a spray device that may be used for delivering opioid medicaments nasally or orally to a patient.

Background of Invention

[0002] 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.

[0003] 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 greater than 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. [0004] 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.

[0005] 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.

[0006] 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. Flowever, 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.

[0007] 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.

[0008] 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.

[0009] 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.

[0010] EP 2011467 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.

[001 1 ] 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.

[0012] 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.

[0013] 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.

[0014] Throughout the description and claims of the specification, the word “comprise” and variations of the word, such as“comprising” and“comprises”, is not intended to exclude other additives, components, integers or steps.

Summary of Invention

[0015] According to one aspect the present invention provides a delivery device for dispensing a dose of liquid medicament, therapeutic or other fluid, the delivery device comprising: a dispenser for manual actuation by a user to dispense the dose, the dispenser having a flow path extending from an inlet to an outlet via a pump such that manual actuation of the pump when primed with the liquid, dispenses a predetermined dosage through the outlet; and a housing assembly with a reservoir for a quantity of the liquid and a coupling to detachably engage the dispenser and form a fluid connection between the reservoir and the outlet; wherein the housing assembly has a priming element configured to act on the reservoir as the coupling engages the dispenser to prime the pump with liquid expelled from the reservoir. [0016] By configuring the dispensing device so that the housing assembly automatically primes the pump of the dispenser when coupling with the housing assembly, the initial actuations of the delivery device will reliably dispense a known dosage of the medicament (or other liquid). This avoids inadequate dosage to patients who may not receive the necessary level of pain relief which can adversely affect their medical care. Furthermore, as discussed above, incomplete dosage can mislead medical personnel if the patient’s response to a perceived pain relief dosage is understated.

[0017] Preferably, the reservoir is tubular and has a plunger for engaging the priming element such that the priming element displaces the plunger to reduce the reservoir volume by an amount required to prime the pump.

[0018] In some embodiments of the invention, the priming element has a priming pin configured for a predetermined length of axial travel along the reservoir, such that the plunger also travels the predetermined length when the coupling engages the dispenser. Preferably, the coupling on the housing assembly has engagement formations for engagement with complementary formations on the dispenser via relative movement of the engagement formations in a direction parallel to the longitudinal axis of the reservoir.

[0019] In a further preferred form, the engagement formations and the complementary formations are configured to inter-engage via relative movement parallel to the longitudinal axis of the reservoir followed by relative rotation of the engagement formations and the complementary formations to engage the dispenser and the housing assembly.

[0020] Preferably, the dispenser and the housing assembly are configured to resist disengagement from each other. Preferably, the dispenser and the housing assembly inter-engage for selective configuration into a locked position preventing user actuation of the pump and an unlocked position allowing user actuation of the group.

[0021 ] Preferably, the pump is manually actuable between a primed condition in which the pump holds a dose of the liquid and a discharged condition for discharging the dose to the outlet, the pump being resiliently biased to the primed condition such that the pump primes with liquid from the reservoir after manually actuating the pump to discharge the liquid.

[0022] Preferably, the priming element has a locating collar connected to the priming pin by one or more frangible bridges, such that the locating collar positions the priming pin until an axial insertion force on the housing assembly fractures the frangible bridges, allowing the priming pin to displace the plunger by the predetermined length of travel needed to prime the pump.

[0023] Preferably, the reservoir has a syringe barrel within a cartridge casing, the syringe barrel holding the liquid medicament and the cartridge casing having the engagement formations for inter-engagement with the complementary formations on the dispenser, the syringe barrel having an outlet connector for fluid connection with the inlet of the dispenser, such that inter-engagement of the housing assembly and the dispenser axially displaces the reservoir relative to the cartridge housing which in turn primes the pump by forcing the plunger onto the priming element resulting in the displacement of the plunger towards the outlet connector of the syringe barrel. Preferably, the cartridge casing has an interior surface shaped to fit with a complementary external surface on the syringe barrel to hold the outlet connector at a fixed position relative to the cartridge casing. In a further preferred form, the external surface of the syringe barrel has longitudinal ribs for sliding inter-engagement with channels in the cartridge casing interior.

[0024] Preferably, the housing assembly has an end cap at a distal end portion of the reservoir opposite the engagement formations, the end cap holding the priming element for engagement with the plunger in the syringe barrel, and the end cap having a peripheral skirt attached to the cartridge housing such that attempts to remove the end cap result in tamper evident damage to the end cap and/or the cartridge housing.

[0025] Preferably, the cartridge casing has snap lock formations to retain the end cap at the distal end portion, the snap lock formations allowing assembly of the endcap onto the distal end portion but not subsequent removal of the endcap without damage to the cartridge casing and/or the end cap. [0026] Preferably, the housing assembly has a removable cap at a proximal end of the reservoir for removal prior to engaging the dispenser, the removable cap having features preventing contact between the engagement formations and the complementary formations, and is not capable of re-attachment to the proximal end of the reservoir once removed. In a further preferred form, the removable cap connects to the proximal end via an integrally formed line of weakness and the features preventing contact are diametrically opposed finger tabs, such that a user applied torque to the finger tabs sheers the removable cap along the line of weakness.

[0027] Preferably, the cartridge casing has at least one window for viewing the syringe barrel and the syringe barrel is transparent to provide visual indication of the liquid medicament level in the syringe barrel.

[0028] Preferably, the housing assembly has a first metal security disc in the end cap and a second metal security disc in the removable cap.

[0029] Preferably, the outlet connector of the syringe barrel is a male luer connector extending from the proximal end, and the inlet of the dispenser is a female luer connector positioned relative to the complementary formations of the bayonet coupling such that the male and female luer connectors form the fluid connection upon inter-engagement of the housing assembly and the dispenser.

[0030] Preferably, the dispenser has a tapered nozzle defining the outlet, and a flange with textured finger grip surfaces on opposing sides for manual actuation of the pump.

[0031 ] In a further preferred form, the dispenser has a spray generating insert attached to the pump outlet such that the liquid is dispensed from the nozzle as a spray.

[0032] According to a second aspect, the present invention provides a housing assembly for use in a liquid medicament delivery device with a manually actuated dispenser, the housing assembly comprising: a reservoir for a quantity of the medicament; a coupling for detachable engagement with the dispenser; and a priming element configured to act on the reservoir as the coupling engages the dispenser to prime the dispenser with medicament expelled from the reservoir.

[0033] Preferably, the priming element displaces volume within the reservoir is displaced during inter-engagement of the housing assembly and the dispenser such that displacement of the priming element reduces the reservoir volume by an amount required to prime the dispenser.

[0034] In another aspect, the invention provides a manually actuated dispenser for use in a medicament delivery device, the dispenser comprising: a flow path extending from an inlet to an outlet via a pump and complementary formations for inter-engagement with a coupling formed on a detachable housing assembly in accordance with second aspect described above, such that inter-engagement between the dispenser and the housing assembly primes the pump with the medicament.

Brief Description of Drawings

[0035] Preferred embodiments of the invention will now be described by way of example only, with reference to the accompanying drawings, in which:

Figure 1 shows a dispensing device according to the present invention;

Figures 2 and 3 show the plan and side elevations respectively for use in the dispensing device shown in Figure 1 ;

Figure 4 is a cross-sectional view of the housing assembly shown in Figures 3, taken along line A-A;

Figure 5 is an axially exploded perspective of the housing assembly shown in Figures 2 to 4;

Figure 6 is a side elevation of the dispenser of the delivery device shown in Figure 1 ; Figure 7 is a cross-sectional view of the dispenser shown in Figure 6, taken along line A-A; and

Figure 8 is an axially exploded perspective of the dispenser shown in Figures 6 and 7.

Detailed Description

[0036] Referring to Figure 1 , the delivery device 2 is shown with the manually actuated dispenser 4 inter-engaged with the housing assembly 6 via the coupling 16. The housing assembly 6 holds a quantity of liquid medicament, therapeutic or other liquid that is drawn into the dispenser 4 by manual actuation of the pump (discussed below) to dispense a spray from the outlet 12 at the tip of the nozzle 14. The delivery device is dimensioned such that the middle finger and the index finger press on the opposing finger grip flanges 8, while the endcap 10 is supported in the palm of the hand. Pressing the dispenser 4 down onto the housing assembly 6 actuates a pump 60 to force the liquid through a spray insert 58 and out the outlet 12. The pump is resiliently biased to return to the primed condition which simultaneously draws the next dose of liquid from the housing assembly 6 and into the pump chamber 68.

[0037] The initial engagement between the housing assembly 6 and the dispenser 4 requires involves a bayonet-style connection at the coupling 16. As best shown in Figures 1 , 6 and 7, the outer peripheral skirt 64 of the dispenser 4 is generally elliptical in cross section. The housing assembly 6 is positioned so that the engagement tabs 22 align with the major axis of the elliptical skirt 64 of the dispenser 4. In this configuration, the housing assembly 6 can be inserted into the skirt 64 (once the removable cap 18 (discussed below) has been removed) as the engagement tabs 22 fit within the long axis of the elliptical cross section. At the same time, the (now exposed) male luer connector 32 engages the female luer connector 62 to form a fluid tight connection.

[0038] The housing assembly 6 is pushed up into the elliptical skirt 64 of the dispenser 4 which in turn pushes the female luer connector 62 towards the pump 60, while also pushing the syringe barrel 30 downwards within the cartridge casing 26. The force applied to the syringe barrel 30 presses on the locating collar 48 of the priming pin 40 to break the frangible bridges 76. This allows the syringe barrel 30 to push the locating collar 48 to the base 46 and the end cap 10, while the priming pin 40 displaces the plunger 24 towards the male luer connector 32. Displacement of the plunger 24 expels liquid medicament from the syringe barrel 30 into the flow path 66 of the dispenser 4. At this stage, the dispenser 4 and the housing assembly 6 are rotated relative to each other so that the engagement tabs 22 are forced into an apertures 80, 82 in the peripheral skirt 64. Skilled workers in field will understand that the structure and polymer of the peripheral skirt 64 and/or the engagement tabs 22 can be selected such that some elastic deformation (with undue force) will allow the tabs 22 to slide across the interior of the skirt 64 until they reach the apertures 80, 82. Here the elastic deformation is released and the tabs 22 protrude into the apertures to retain the dispenser 4 on the housing assembly 6.

[0039] The apertures are asymmetrical with a tall section corresponding to an unlocked position 80 for the dispenser 4, and a short section corresponding to a locked position 82 for the dispenser. During initial inter-engagement of the dispenser and the housing assembly, the female luer connector 62 is pressed up into the discharge position as the syringe barrel 30 is forced down into the cartridge housing 26 (as discussed above). As the dispenser and the housing assembly are then rotated relative to each other, the tabs 22 are relatively high in the peripheral skirt 64 and both reach the top of the tall section 80. Here the compression applied to the dispenser is released and the return spring (or similar resilient bias) in the pump 60 pushes the dispenser away from the housing assembly. This moves the tabs 22 from the top of the tall section 80 of the aperture to the bottom of the tall section. Here the dispenser may be rotated a few degrees so that the tabs 22 move across into the short section 82 where their movement is more restricted, thereby locking the dispenser from being manually actuated. This is a useful precaution against unintentional actuation of the dispenser 4, or a child safety lock particularly if a degree of resistance in moving from the locked position 82 to the unlocked position 80 is incorporated.

[0040] Figures 2 to 5 illustrate the features of the housing assembly 6 in detail. The housing assembly 6 is provided in the form of a cartridge intended for a single use with the dispenser 4. Once the housing assembly 6 is empty, the dispenser 4 is rotated to a locked position and the complete device 2 is carefully disposed as there may be some residual medicament (e.g. opioids) in the syringe. However, the invention equally applies to a situation in which the empty cartridge is simply replaced and the dispenser is re-used. The top or proximal end of the housing assembly has a removable cap 18 that is integrally moulded and connected with the cartridge casing 26 via a line of weakness 34 (best seen in Figure 4). On diametrically opposed sides of the removable cap 18 are protruding finger tabs 20. Prior to inserting the housing assembly 6 into the dispenser 4 as discussed above, the user twists the finger tabs 20 to apply a torque to the line of weakness 34 which sheers away from the cartridge casing 26. This provides a tamper evident feature as the removable cap 18 cannot be replaced once the line of weakness 34 has been fractured. Furthermore, the finger tabs 20 not only provide the protrusions to manually apply torque but also act as guarding formations to prevent inter-engagement of the dispenser 4, and the housing assembly 6 until the cap 18 is removed.

[0041 ] Following removal of the cap 18, the upper security disc 54 and luer cover 50 are also removed. The upper security disc 54 is typically metal or another hardened material to prevent tampering with the medicament via insertion of a needle. The luer cover 50 seals the male luer connector 32 at the outlet of the syringe barrel 30. The luer cover 50 is preferably a relatively pliable polymer material to provide a fluid seal and for compressive insertion into a longitudinally ribbed sleeve 52 positioned about the male luer connector 32.

[0042] The ribbed sleeve 52 slides into complementary channel 72 formed within the cartridge casing 26. This provides reliable positioning of the male luer connector 32 relative to the integrally molded engagement tabs 22. During inter-engagement of the dispenser 4 and the housing assembly 6, the closely toleranced positioning of the male luer connector 32 provides reliable engagement with the female luer connector 62 of the dispenser (see Figure 7).

[0043] The syringe barrel 30 provides a reservoir 30 for the medicament which is sealed at the upper end by the luer cover 50 and at its lower end by a plunger 24. The plunger 24 is slides towards the male luer connector 32 of the syringe barrel to incrementally reduce the reservoir volume and expel a predetermined volume of medicament through the male luer connector 32. The vacuum caused by the actuation of the spray pump 60 (or rather the automatic re-priming of the pump 60 immediately following actuation) draws the plunger along the syringe barrel as the medicament is dispensed. As there are no air bubbles in the syringe or upstream of the pump 60, the dispenser device 2 can be used in any orientation and will deliver a complete dose of medicament with each actuation. This has clear advantages in situations where the patients are themselves trapped in awkward positions.

[0044] The end cap 10 is carefully designed to avoid removal from the distal end of the cartridge casing 26, to prevent access to the syringe barrel 30 therein. The end cap 10 slides up to the abutment flange 38 on the cartridge casing 26, where the outwardly biased snaplock formations 44 snap into the internal snaplock recess 78 at the base 46. This provides a tamper resistant feature in that the end cap cannot be subsequently removed for access to the syringe barrel 30 without obvious damage to the cartridge casing 26 and/or the end cap 10.

[0045] Referring to Figures 6, 7 and 8, the features of the dispenser 4 are shown in detail. The dispenser 4 defines a flow path 66 extending from an inlet in the form of the female luer connector 62 to an outlet 12 at the upper end of the nozzle 14. The length and diameter of the nozzle 14 is selected for nasal and/or oral delivery of the medicament. However, other outlet configurations are also envisaged for dispensers to deliver the contents of the reservoir to other areas, such as ears, eyes or a close topical application. When not in use, the nozzle 14 is covered by a nozzle cap 56 to prevent ingress of contaminants via the outlet 12.

[0046] At the base of the nozzle 14 on either side of the dispenser 4 is a flange defining a pair of finger grip surfaces 8. Depending from the periphery of the finger grip surfaces 8 is the outer peripheral skirt 64, in which the coupling features 16 are formed. The nozzle 14 and the outer skirt 64 are preferably a single piece of polypropylene moulding which houses a spray insert 56, pump 60 and female luer connector 62. As the dispenser 4 and the housing assembly 6 inter-engage as described in detail above, the exposed end of the male luer connector 32 accurately aligns with the female luer connector 62. The axial compression on the base 46 of the end cap 10 drives the housing assembly 6 up into the outer skirt 64 of the dispenser 4 against the resilient bias on the female luer connector 62 provided by the pump 60. Skilled workers familiar with the production of these products understands that the spray insert 58, pump 60 and female luer connector 62 are well known components manufactured by a wide variety of companies. For example, suitable spray pumps are produced by Bona PHARMA of Changxin Road Guaunha Street, Langhua Area, Shen Zen 5181 10, Peoples Republic of China. Other suitable pumps are produced by AptarGroup Inc., and Valois Corp of Connecticut U.S. The operation and function of spray pumps of this type are relatively universal but typically they are fitted with a fitted with a simple‘dipstick’ tube from the pump to the reservoir of liquid, instead of the female luer connector used in the present invention. This luer connector is added to the spray actuator such that it is resiliently biased away from the pump 60. Manually depressing the pump via finger grips 8 dispenses the contents through the spray insert 58 and subsequently the pump is biased back to a primed position, simultaneously re-priming the pump chamber with medicament from the syringe 30.

[0047] With the housing assembly 6 forced axially into the dispenser 4 and then twisted through an angle of relative rotation, the coupling engages and is maintained in engagement by the return force on the female luer connector 62 pressing onto the male luer connector 32. However as discussed above, when axially forcing the housing assembly 6 into engagement with the dispenser 4, the frangible bridges 76 connecting the priming pin 40 to the locating collar 48 are fractured such that the plunger 24 is displaced by the predetermined length of travel. In this way, the specified volume of medicament expelled by the predetermined travel of the plunger 24, ensures that the pump 60 is fully primed upon the initial insertion of the housing assembly 6. No initial priming pumps of the spray are needed to ensure the pump is delivering a full dose of medicament with every actuation. Furthermore, it will be appreciated that the fracture of the frangible bridges 76 and the inter-engagement between the tabs 22 and the dispenser 4 provide the user with distinct haptic feedback indicating correct assembly of the dispensing device 2.

[0048] As doses of the medicament are dispensed, the plunger vacuum created by the pump 60 in the interior 36 of the syringe barrel 30, incrementally draws the plunger 24 towards the male luer connector 32. A viewing window 28 formed in the cartridge casing 26 allows the user or medical staff to monitor the medicament levels and gage the total volume of medicament dispensed during treatment of a patient. Conveniently, the plunger 24 is a colour that strongly contrasts with the medicament and remainder of the cartridge housing 26 for visual clarity. Similarly, the syringe barrel 30 may have markings that are viewed through the window 28 to indicate the remaining volume of medicament.

[0049] The present invention has been described herein by way of example only. Skilled workers in this field of technology will readily recognise many variations and modifications which do not depart from the spirit and scope of the broad inventive concept.