Pressurized gas driven drug transfer and resuspension apparatus and method

Abstract

A pressurized gas driven medicament transfer and resuspension apparatus and method is described. The method comprises: puncturing a pressurized gas cylinder by inserting the cylinder into a transfer device; introducing pressurized gas from the punctured pressurized gas cylinder into the cylinder; causing fluid to flow from the cylinder under pressure from the gas; and causing the fluid to flow from the cylinder into an injection device under the force of the pressurized gas.

Description

[0001] Divisional Application Instructions

[0002] This application is a divisional application of a PCT invention patent application with an international application date of March 24, 2016, a Chinese national phase entry date of September 26, 2017, a national application number of 201680018568.3, and an invention name of “Pressurized gas-driven drug transfer and resuspension apparatus and method”.

[0003] CROSS-REFERENCE TO RELATED APPLICATIONS

[0004] This application claims priority to and the benefit of U.S. Provisional Application No. 62 / 138,762, filed on March 26, 2015. Technical Field

[0005] The present subject matter generally relates to an apparatus and method for transferring and / or mixing a liquid or non-reconstituted form of a medicament in a vial. Background Art

[0006] Drugs, biologics, vaccines, antibiotics and other medical materials ("medicaments") intended for injection into a subject are typically provided in sealed bottles from which the medicament must be removed and transferred to an injection device prior to injection. In some cases, the medicament is in liquid form, and in other cases, it is in dry or powdered form, such as lyophilized form, and should be reconstituted or resuspended with a liquid diluent before it can be removed from the bottle. In this specification, "resuspended" is used in a comprehensive sense, thereby including reconstitution and dilution.

[0007] As with injection devices for injecting a medicament into a subject, devices for transferring and / or resuspending a medicament supplied in a vial have been the subject of significant development. Examples of both are described in PCT International Application No. PCT / US2014 / 042627, entitled "Vial Transfer and Injection Apparatus and Method," published on December 24, 2014 as PCT Publication No. WO2014204894 and incorporated herein by reference in its entirety. Various embodiments of transfer and mixing or resuspending devices and injection devices are disclosed in detail therein. The transfer and resuspending device shown therein employs a spring-loaded piston and a gas cylinder to transfer medicament and / or diluent and / or resuspend medicament between a vial or vials and an injection device. While these devices work well, further cost reduction and / or size reduction and / or simplification are still desirable. Summary of the invention

[0008] According to one aspect of the present subject matter, a pressurized gas from a source is employed to transfer, mix, and / or reconstitute a medicament contained in a vial. The pressurized gas source may be, for example, a pressure vessel such as, but not limited to, a pre-filled pressurized gas cartridge or gas cylinder. More specifically, in one aspect, a method of transferring a fluid from a vial containing a fluid to an injection device is provided. The method may include introducing a pressurized gas from the pressure vessel into the vial; causing the fluid to flow from the vial under pressure from the gas; and causing the fluid to flow from the vial into the injection device under the action of the pressurized gas.

[0009] In a further aspect, two or more bottles can be used and the fluid from the first bottle flows into the second bottle to combine or mix with the contents of the second bottle and the combined fluid flows into the injection device or flows into one or more other bottles and the injection device. In order to reconstitute the lyophilized drug, the first bottle can contain a liquid diluent and the second bottle contains the drug. In order to dilute the liquid medicament, the first or second bottle can contain a diluent and the other bottle contains the liquid medicament. In order to provide a drug mixture or "mixture", each bottle can contain a liquid medicament. Other variations or combinations may exist, and other bottles are used. A common feature is the use of pressurized gas such as from a pre-filled pressurized gas cylinder or barrel to provide energy or force for moving fluid from the bottle to the bottle and into the injection device.

[0010] The injection device may include an expandable reservoir, and the resulting fluid, such as a combined diluent and medicament or a combined liquid medicament, flows into the expandable reservoir under pressure from the pressurized gas. The pressure may optionally cause the reservoir to expand as it fills with the fluid or combined diluent and medicament, thereby effectively filling the injection device for subsequent use by medical personnel or the subject themselves.

[0011] In another aspect of the present disclosure, a medicament transfer apparatus for transferring a fluid from a bottle containing the fluid to an injection device including a medicament reservoir is disclosed. The apparatus includes a pressurized gas source such as, but not limited to, a pressure vessel such as a prefilled pressurized gas cartridge or gas cylinder, at least one bottle receiving station, and a medicament injection device receiving station. A gas flow path can communicate between the gas source and the bottle receiving station and a fluid flow path can communicate between the bottle receiving station and the medicament injection device receiving station.

[0012] The medicament transfer device can have more than one bottle receiving station and can include, for example, a first bottle receiving station and a second bottle receiving station, or more. The gas flow path can be communicated between a pressurized gas source and a first bottle receiving station that receives a bottle containing a liquid such as a diluent or a liquid medicament. The second and other bottle receiving stations can be configured to receive bottles containing any appropriate contents such as a lyophilized drug to be reconstituted by a diluent, a liquid medicament to be diluted by a diluent or mixed with another liquid medicament, or a variation thereof. The fluid flow path can be communicated from one bottle receiving station to another bottle receiving station to allow the desired fluid flow of a diluent, a medicament, or a combination thereof. The fluid flow path is also communicated between the bottle and the injection device receiving station so that the resulting fluid, whether it is a reconstituted lyophilized drug, a diluted medicament, or a liquid medicament mixture, can flow into the injection device. The kinetic energy or force for transferring fluid between the bottles and to the injection device receiving station is a pressurized gas from a pressurized gas source.

[0013] The medicament transfer apparatus may also include an injection device removably secured to the device receiving station.The injection device may include a reservoir such as a reservoir capable of expanding under fluid pressure due to force from a pressurized gas.

[0014] According to another aspect of the present disclosure, another resuspension device for resuspending the pharmaceutical contents (such as microaggregates) of a bottle of the type having an open end sealed by a septum is disclosed. This resuspension device includes an outer cover, which includes a diluent port, a gas port, an exhaust port, and a bottle receiving station. It also includes a first pointed inner cavity and a second pointed inner cavity extending from the bottle receiving station to puncture the bottle septum when the bottle is received at the bottle receiving station. The gas flow path in the outer cover is connected between the inlet port and the first pointed inner cavity; the diluent flow path is connected between the diluent port and the first pointed inner cavity; and the exhaust flow path is connected between the exhaust port and the second pointed inner cavity. A hydrophobic filter is cooperatively associated with the exhaust flow path to filter gas passing through the exhaust flow path and substantially prevent liquid from leaking from the exhaust flow path.

[0015] Related to this aspect, a method of resuspending the contents of a medicament of a bottle is also provided. The method comprises: introducing a diluent into the bottle; injecting a gas under pressure into the bottle below the level of the diluent in the bottle to cause agitation of the diluent and the medicament; exhausting the gas from the bottle; and continuing the injection and exhaust until the medicinal contents are substantially resuspended. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] The above aspects and many other aspects of the present subject matter are disclosed in the following description of the non-exclusive examples shown in the accompanying drawings, in which:

[0017] Figure 1-12It is an exemplary view of PCT International Application No. PCT / US2014 / 042627, entitled “Vial Transfer and Injection Apparatus and Method,” which was published on December 24, 2014 as PCT Publication No. WO2014204894 and is included for background and general disclosure purposes.

[0018] Specifically, Figure 1 is a perspective view of a single vial system including a single vial holder, transfer apparatus, and injection device system embodying the present subject matter.

[0019] Figure 2 is a perspective view of a dual vial system including a dual vial holder, transfer apparatus, and injection device system embodying the present subject matter.

[0020] Figure 3 Includes a perspective view of a single bottle holder with a removable top included, a cross-section of a single bottle holder with a removable top included, and a perspective view of a single bottle holder with the removable top and bottle cap removed.

[0021] Figure 4 A perspective view with the removable top included, and a cross section of the double bottle holder with the removable top and bottle caps removed.

[0022] Figure 5 yes Figure 2 A section in the area of ​​a bottle holder showing the position of the bottle access member relative to the septum of the bottle.

[0023] Figure 6 yes Figure 1 Section in the area of ​​the bottle holder showing the bottle access member piercing the septum of the bottle.

[0024] Figure 7 yes Figure 1 A perspective view of the transfer apparatus is shown, illustrating the vial holder and injection device receiving area.

[0025] Figure 8 yes Figure 5 A close-up of a vial access component that punctures the septum of a vial, with a collapsible vial access component shield.

[0026] Fig. 9 is Figure 2 Schematic diagram of a dual bottle transfer system in which there is a first bottle, a second bottle, a transfer device with a first and a second variable pressure chamber, and an injection device including a fluid path.

[0027] Fig.10 It is in the pre-fire position. Figure 2 cross section.

[0028] Fig.11 A device having a drug bottle, a transfer device having a first variable pressure chamber and an injection device including a fluid path, wherein Figure 1 Schematic diagram of the single bottle transfer system in .

[0029] Fig.12 yes Figure 1 cross section.

[0030] Fig.13 is a flow chart of a method for pressurized gas driven transfer of a medicament from a vial to an injection device in accordance with the present subject matter.

[0031] Fig.14 is a flow chart of a method of pressurized gas transfer of a medicament from a vial to an injection device in accordance with the present subject matter.

[0032] Fig.15 is a perspective view of a single bottle transfer device embodying one aspect of the present subject matter.

[0033] Fig.16 yes Fig.15 A perspective view of the device with the outer cover partially removed to better view the interior.

[0034] Fig.17 yes Fig.15 Horizontal cross-sectional view of the device.

[0035] Fig.18 is a perspective view, partially in cross-section, of an alternative single bottle transfer apparatus embodying one aspect of the present subject matter.

[0036] Fig.19 are in different operable positions, Fig.18 A partial cross-sectional perspective view of the device.

[0037] Fig. 20 is a flow chart of a method according to the present subject matter of pressurized gas driven transfer and mixing of contents from two bottles and transfer to an injection device.

[0038] Fig.21 is a flow chart of a method of transferring and mixing pressurized gas from the contents of two bottles and transferring to an injection device in accordance with the present subject matter.

[0039] Fig. 22 is a perspective view of a dual bottle transfer apparatus embodying one aspect of the present subject matter.

[0040] Fig.23 yes Fig. 22 A perspective view of the device with the outer cover partially removed to better view the interior.

[0041] Fig.24 yes Fig. 22 Horizontal cross-sectional view of the device.

[0042] Fig.25 is a cross-sectional view of another system / device that can be used to resuspend a pharmaceutical agent for injection. DETAILED DESCRIPTION

[0043] For background and general disclosure purposes, Figure 1-12 The various functional features shown may be employed in combination with the present subject matter. Figure 1 and 2 As described in more detail below, a disposable, single-use, single-bottle transfer and injection system 1 is Figure 1 2 and may include a single bottle holder 2, a transfer device 3 and an injection device 7. A disposable, single-use, dual bottle mixing, transfer and injection system 4 is shown in Figure 2 1 and may include a dual vial holder 5, a transfer device 6 and an injection device 7. As previously mentioned, each of these aspects has independent utility and may be claimed independently and / or in combination or in sub-combinations.

[0044] refer to Figure 3 and 4 , the single bottle holder 2 shown includes a housing 8 including side walls 9, end walls 10 and apertures or viewing windows 11. Alternatively, the bottle holder 2 material may be transparent to allow the contents of the bottle 12 to be viewed. The housing 8 is shaped to define at least one or two or more bottle receiving cavities (also referred to as stations or zones) 13 to be viewed in a manner such as Figure 4 Each area 13 shown in the vial holder 5 can be securely held in the vial 12. The cavity 13 in the vial holder 5 can be sized to receive standard injectable vials 12 having different sizes, such as from 1 to 30 ml. The vials 12 can have the same size or different sizes and can contain any desired injectable 14.

[0045] exist Figure 4In the double bottle holder 5 illustrated in FIG. 1 , as a non-limiting example, the bottles may include a bottle 15 of a powdered, lyophilized or liquid drug and a bottle 16 of a liquid or diluent. Variations may exist, and alternatively, for example, each bottle may contain a liquid medicament, or one bottle may contain a diluent and the other may contain a concentrated liquid medicament. The bottle holder 5 may have bottles prepackaged and assembled therein by, for example, a drug manufacturer, or the bottles may be inserted into the bottle holder 5 by an end user or by a medical professional such as a pharmacist or nurse. The bottle holder 5 may have appropriate markings and / or features to allow only specific bottles to be assembled in specific cavities 13. For example, a powdered drug bottle 15 may be inserted into a specific cavity 13 of the bottle holder 5 and a diluent bottle 16 may be inserted into another cavity 13 of the bottle holder 5. The aperture or viewing window 11 in the bottle holder 5 allows direct visualization of the contents 14 of the bottle.

[0046] refer to Figure 3 and 4 As a further alternative, the vial holder 5 may be an assembly of separate vial holders 2, each of which holds a single vial 12. For example, an injectable manufacturer may preassemble vials 12 in separate vial holders 2, which can then be combined with the vial holder 2 of another vial 12 when injected, if desired. For example, a pharmaceutical manufacturer may provide a lyophilized drug 15 in its own vial holder 2 and a diluent 16, such as sterile water or saline, in a separate vial holder 2. The user or medical professional can then connect the separate vial holders 2 as needed to form a vial holder for connection to the vial holder 2. Figure 2 The bottle holder assembly 5 of the transfer device 6 is shown.

[0047] Come back for reference Figure 3 , the bottle holder 2 may include a removable cap 17 that normally covers and protects the end of the bottle 18 during shipping and storage. A typical standard commercial bottle 12 includes a pierceable septum 19 located in the neck of the bottle for accessing the bottle contents 14 covered by a removable cap or closure 20. The removable cap 17 may be configured to engage the bottle cap 20 so that removal of the cap simultaneously removes the bottle cap 20 and exposes the bottle septum 19 to access the contents 14 after any preservative wipe of the septum 19 that the user may deem necessary. The bottle holder 2 may have the bottle 12 recessed therein so that after the bottle cap 20 is removed by the cap 17, the pierceable septum 19 is recessed within the bottle holder 2 to reduce the risk of puncturing the bottle when inserting the bottle holder 2 as in Figure 1 The transfer device 3 shown in FIG. 1 is previously exposed to the opportunity of contamination by the user. This system can be applied to both single bottle holders 2 and double bottle holders 5.

[0048] refer to Figure 3, the bottle holder 2 may include an interlock 27 to prevent the bottle 12 from being removed once the bottle 12 is inserted into the bottle holder 2. This helps prevent the bottle 12 from falling out or being accidentally removed during handling.

[0049] refer to Figure 5 , after the bottle caps are removed and the bottles 15, 16 are installed in the bottle holder 5 by the device manufacturer, the bottle holder 5 can be assembled to the transfer device 6. The exposed bottle septum 19 is held in close proximity to the bottle access member 21, 52 prior to actuation. This configuration provides convenience by eliminating the need for the user to remove the bottle caps, wipe the bottle tops 19, and assemble the bottle holder 5 to the transfer device 6 prior to using the system 4.

[0050] refer to Figure 6 , the bottle holder 2 can be packaged separately from the transfer device 3. In this case, the user will remove the bottle cap using the removable cover 17, wipe the bottle top 19 (if necessary) and assemble the bottle holder 2 into the transfer device 3. Figure 6 As shown in FIG. 1 , the bottle holder 2 may include a lock-out feature 22 that interacts with the transfer device 3 to prevent the bottle holder 2 from being inadvertently pulled out of the transfer device 3 after being actuated by a user.

[0051] refer to Figure 5 , the bottle holder 5 is preferably assembled to the transfer device 6 to configure the bottles 15, 16 upside down in a vertical position. This allows any liquid 23 in the bottle to communicate directly with the bottle access components 21, 52 after insertion into the bottle holder 5. This also forces the air 24 to reach the top of the bottle in this orientation. To encourage the septum 19 to remain uncontaminated after the bottle cap is removed and before the bottle holder 5 is inserted, the exposed bottle septum 19 can be recessed into the bottle holder 5 to prevent contamination as in Figure 4 This configuration can be applied to both single bottle holder and double bottle holder configurations.

[0052] refer to Figure 6 , the bottle holder 2 is preferably mechanically configured with an insertion feature 25 in the transfer device 3 to actuate like an on / off switch, i.e., to have only two states, on and off, such as a light switch. This can prevent a user from pushing the bottle holder 2 halfway into the transfer device 3 and not allowing the bottle access member 21 to pierce the septum 19 and allow communication between the contents 14 of the bottle 12 and the transfer device 3. Additionally, the bottle holder 2 can interact with an interlock 26 in the transfer device 3 to lock the bottle holder 2 in a closed position after the bottle holder 2 is fully inserted to prevent the bottle holder 2 from being removed from the transfer device 3 after insertion.

[0053] refer to Figure 7, the transfer device 3 includes an outer cover 28 and defines a bottle holder docking area or a first receiving station 29 and an injection device docking station or a second receiving station 30 (for a removable injection device). In the illustrated structure, the bottle holder docking station 29 and the injection device docking station 30 are at opposite ends of the transfer device outer cover 28.

[0054] refer to Figure 7 , the transfer device 3 can have an outer cover 28 integrated into a packaging 31 of the system. The outer packaging 31 can essentially form the bottom wall and side walls of the transfer device outer cover 28. All operating steps in the use of the system until the injection device is removed can occur in this packaging 31. This can provide cost reduction and increase ease of use for the user. Additionally, incorporating the entire transfer device 3 into the packaging 31 eliminates possible user errors that can occur if the user is required to remove the transfer device 3 from the packaging 31. The packaging 31 can include a plastic barrel or tray that contains the system. In turn, the packaging 31 can include everything within a shipping carton 32 that contains the entire system.

[0055] refer to Figure 7 , the transfer device 3 includes a vial holder docking area 29, which may include an elongated vial access member or piercing member 21. This access member or piercing member 21 can be configured as a pointed or blunt cannula or needle. Figure 8 , the bottle holder 5 with the bottle 12 coupled thereto is shown inserted into the bottle docking station 29 and the bottle access component 21 pierces the bottle septum 19 to allow access to the contents 14 of the bottle 12. The bottle access component 21 may include a foldable seal 33 to maintain sterility of the bottle access component 21 and the fluid path prior to actuation. The foldable seal 33 may also be coupled and sealed on the outside of the bottle 12 relative to the bottle access component 21 to maintain sterility prior to actuation.

[0056] refer to Figure 8, the bottle access component 21 of the transfer device 3 can include a multi-lumen tube 34 to communicate with the internal fluid path 35 of the transfer device 3. The bottle access component 21 preferably includes an inlet tube 36 that allows air or fluid to enter the bottle 12 and an outlet tube 37 that allows air or fluid to leave the bottle 12. These inlet tubes 36 and outlet tubes 37 can be separate and distinct and communicate with different fluid paths in the transfer device 3. Due to the vertical orientation of the bottle 12 in the upside-down position, the lumen opening 38 in the bottle access component 21 can be oriented so that the inlet tube opening 36 is above the outlet tube opening 37. This orientation allows for the introduction of pressurized air or liquid through the upper inlet tube 36 and the output of the bottle contents 14 through the lower output tube 37. In addition, the outlet opening 37 can be positioned adjacent to the septum 19 near the bottom of the bottle 12 to encourage the entire contents 14 of the bottle 12 to enter the outlet port 37 and be removed from the bottle 12.

[0057] refer to Fig. 9 and 10 The transfer device 6 is configured to perform, preferably automatically, all the steps necessary to transfer, mix and / or reconstitute (if necessary) the injectables 14 contained in the bottles 15, 16 and transfer the mixture to the injection device 7 after the user starts the process. The transfer device 6 is configured and preferably includes a propulsion system or multiple propulsion systems, such as an electrically (e.g., battery-powered) or mechanically (e.g., spring-loaded) actuated pump to guide the diluent from the diluent bottle 16 into the injectable powder bottle 15 and guide the injectables 14 into the injection device 7 through the transfer device 6.

[0058] refer to Fig. 9 and 10 , the transfer device 6 may also include an array of internal fluid paths 35 as needed to perform any transfer, reconstitution, mixing, dilution or other processing of the injectable 14 and transfer it from the vials 15, 16 in the vial holder 5 to the injection device 7. The fluid paths 35 may include flexible or rigid conduits or tubes. These fluid paths 35 may also include check valves, filters, flow restrictors or other devices 40 to guide the drug from the vials 15, 16 to the injection device 7 through the transfer device 6.

[0059] refer to Fig. 9 and 10 , the transfer device 6 may include a variable volume pressure chamber or cylinder having a movable spring loaded piston therein and which communicates directly with the internal fluid path 35. Such chambers will not be required in the embodiments described in the Summary of the Invention and in more detail below where a pressurized gas source is employed to cause fluid transfer and / or mixing. Fig. 9 and 10In an embodiment of the invention, the chamber capacity for each variable volume chamber can be defined by the chamber diameter and the position of the piston in the chamber. The first pressure chamber 41 in the transfer device 6 can preferably have an initial volume set by the manufacturer in the range of 1 to 30 milliliters. The initial contents of the first pressure chamber 41 can preferably include air 45. The piston 43 can be driven by a compression spring 44 in the first pressure chamber 41 whose volume is defined and set by the manufacturer. The spring-loaded piston 43 can have an appropriate size and configuration to generate a static air pressure of 1 to 50 psi in the first pressure chamber 41. The volume of the air 45 will depend on the diameter of the chamber 41 and the stroke position of the piston 43 during operation. This pressure will depend on the relative volume of the air 45 displaced by the piston 43 and the force applied by the spring 44. In other words, the force applied by the spring 44 multiplied by the area of ​​the piston 43 inside the chamber 41 will determine the static pressure in the chamber 41. The force applied by the spring 44 at its compaction height or at the beginning of the stroke may be much greater than the force applied by the spring 44 at the end of its travel. The spring 44 may be appropriately sized to control the rate at which the air 45 is exhausted from the pressure chamber 41 and thus the fluid transfer speed in the transfer device 6. The first pressure chamber 41 is preferably configured to exhaust all of the air 45 from the first pressure chamber 41. Alternatively, a flow restrictor 55 in the output path 35 of the pressure chamber 41 can be used to control the rate at which the air 45 is exhausted from the pressure chamber 41.

[0060] refer to Fig. 9 and 10 , the chamber volume for the second pressure chamber 42 can be set by the manufacturer. Alternatively, the filled chamber volume for the second pressure chamber 42 can be set by the user in the range of 0.5 to 30 ml using a dosage selector or volume controller 48 at the time of use. The spring-loaded piston 46 in the second pressure chamber 42 can have an appropriate size and configuration to generate a pressure of 1 to 200 psi in the second pressure chamber 42. The dosage selector or volume controller 48 allows the user to select a prescribed dose to be injected by the injection device 7 by setting the filling volume of the chamber 42. The dosage selector 48 can have any appropriate configuration. The dosage selector 48 can be directly connected to the pressure plunger assembly chamber 93 that can move inside the pressure chamber 42. Once the piston has reached a position corresponding to the filling volume setting, the trigger 49 in the pressure plunger assembly 93 releases the piston 46 in the second pressure chamber 42. The user selects the desired dose position in the second pressure chamber 42 by moving the dose selector 48 which positions the pressure chamber plunger assembly 93 to define a fill chamber volume equal to the desired injection dose. Alternatively, the position of the pressure plunger assembly 93 may have been set by manufacture corresponding to the dose to be delivered and the user operates the device without making dose adjustments.

[0061] refer to Fig. 9 and 10 , a transfer device 6 for a dual bottle system 4 providing mixing and transferring includes a bottle holder 5 with a first bottle 16 and a second bottle 15, a first variable volume pressure chamber 41, a second variable volume dosage pressure chamber 42, a fluid path 35 and a check valve 40 to guide air from the first pressure chamber 41 into the first bottle 16 and the contents 23 of the first bottle 16 into the second bottle 15 and the resulting mixture 14 in the second bottle 15 into the second pressure chamber 42, and the mixture 14 is then transferred to the injection device 7.

[0062] refer to Figure 8 , allowing release when the bottle holder 5 is fully inserted into the transfer device 6 and the bottle access member 21 is subsequently guided by the user through the septum 19 and into the bottle chamber 12 Fig.10 A pressure chamber trigger 50 is shown.

[0063] refer to Fig. 9 and 10, the release of the trigger 50 then releases the first pressure chamber spring 44, thereby allowing the first pressure chamber piston 43 to advance in the first pressure chamber 41, which causes the air 45 in the first pressure chamber 41 to be forced through the inlet tube 36 of the first bottle access component 21 and into the first bottle 16 through the internal path 35 in the transfer device 6. As more air 45 is squeezed out of the first pressure chamber 41 and into the first bottle 16 through the inlet tube 36, the air 45 rises to the top of the first bottle 16 due to its vertical orientation within the bottle holder 5. The increased air pressure in the first bottle 16 causes the fluid 23 in the bottle 16 to be expelled through the outlet tube 37 of the first bottle access component 21 and through the inlet tube 51 of the second bottle access component 52. The fluid 23 entering the second bottle 15 from the first bottle 16 mixes with the contents 54 of the second bottle 15 containing liquid or powdered medicament and exits through the outlet tube 53 of the second bottle access component 52 and into the second pressure chamber 42. In the same manner within this reconstitution configuration, the plunger 43 advancing in the first pressure chamber 41 continues to push the first fluid 23 and then air 45 mixture through the first bottle 16 and into the second bottle 15. The increased air pressure in the top of the second bottle 15 causes the reconstituted or other mixture 14 in the bottom of the second bottle 15 to be expelled into the second pressure chamber 42. A "popoff" or check valve 40 or other type of valve may be present on the outlet tube 53 of the second bottle access member 52 to force all of the contents 23 of the first bottle 16 into the second bottle 15 before the contents 14 of the second bottle 15 are expelled into the second pressure chamber 42. The valve will not open until the pressure corresponding to the plunger 43 has substantially pushed all of the air 45 out of the first pressure chamber 41. This ensures that the contents 54 of the second bottle 15 can be thoroughly mixed with the contents 23 of the first bottle 16 before the mixture 14 leaves the second bottle 15 and enters the second pressure chamber 42. Alternatively, a flow restrictor 55 may be used in the fluid path 35 to delay transfer and increase mixing time.

[0064] refer to Fig. 9 and 10, the injectable drug 14 flows from the second bottle 15 into the second pressure chamber 42 after mixing, dilution and / or reconstitution, filling the chamber 42 to the extent permitted by the position of the piston 46, as selected by the user or manufacturer using the dose indicator 48, corresponding to the desired dose. When the desired volume of the second pressure chamber 42 has been achieved, the second pressure chamber trigger 49 releases the spring 47 and presses the piston 46 forward, thereby expelling the selected dose of the injectable drug 14 under pressure into the injection device 7. Calibration of the dose volume shown on the dose selector 48 and the actual dose received by the user may be required to account for fluid losses in the internal path 35 of the transfer device 6. The injection device 7 is now full and ready to be removed from the transfer device 6.

[0065] refer to Fig.11 and 12 , an alternative transfer device 3 within a single bottle system 1 is provided that does not perform mixing but merely transfers the fluid 14 from a single bottle 15 to an injection device 7. This alternative transfer device 3 comprises a bottle holder 2 with a single bottle 15, a variable volume pressure chamber 56, a fluid path 35 and a check valve 40 to direct the contents 14 from the bottle 15 to the injection device 7. The inlet tube 36 of the bottle access component 21 leads to the environment 57 to allow air 58 to enter the bottle 1. The outlet tube 37 of the bottle access component 21 is connected to the pressure chamber 56.

[0066] refer to Fig.11 and 12 , the user fully inserts the bottle holder 2 into the transfer device 3 causing the bottle access member 21 to be introduced through the septum 19 of the bottle 15 to access the contents 14 of the bottle 15. This also triggers the release of the pressure chamber trigger 59. The pressure release trigger 59 releases the plunger 60 within the pressure chamber 56 connected to the extraction spring 61. The extraction spring 61 forces the plunger 60 to retract and extract the fluid 14 from the bottle 15 and fill the pressure chamber 56. The specified amount of fluid 14 extracted by the chamber 56 can be set by the manufacturer by limiting the retraction of the plunger 60. Alternatively, the chamber 56 can be configured to extract all of the fluid 14 from the bottle 15 by retracting the plunger 60 to its full stroke. Once the plunger 60 reaches a set position within the pressure chamber 56, it interacts with the dispensing trigger 62, which releases the dispensing spring 63 to force the liquid 14 out of the pressure chamber 56 and into the injection device 7. The check valve 40 can be used to prevent the fluid 14 from flowing back into the bottle 15.

[0067] Pressurized gas driven transfer and / or mixing

[0068] according to Figure 13-24With the present subject matter shown, the transfer and / or mixing and resuspension is driven by a source of pressurized air, such as a pressure vessel, which may be in the form of a pre-filled pressure cylinder or cartridge. This allows the elimination of a variable volume pressure chamber or cylinder with a movable spring-loaded piston as described above and potentially reduces the cost and size of the transfer and mixing / resuspension equipment.

[0069] Now turn to Fig.13 This flow chart provides an overview of a single bottle fluid transfer method and generally depicts certain exemplary steps when using a pressurized gas source to power the transfer. The structures used to perform the process or method and more specific aspects of these structures will be described later.

[0070] Fig.13 Each step in the flow chart may not be required in all embodiments. As reflected in the flow chart, a vial containing a liquid medication is inserted into a vial receiving station that may have a transfer device with a spike for piercing the vial septum and accessing the contents. The spike may have two lumens, one for gas entry and the other for medication exit, or two separate spikes may be used.

[0071] The method is initiated by the user by actuating a gas trigger mechanism that can have a variety of different configurations. As explained later, the trigger mechanism can be actuated when the bottle is inserted into the bottle receiving station or thereafter. For example, such insertion can release the spring force that forces the lancet or puncture needle to pass through a sealing diaphragm or cap associated with the pre-filled pressure gas bottle or cartridge. Alternatively, the user's own force can be used to press the pre-filled gas bottle and puncture needle together to access the pressurized gas when the bottle is inserted into the receiving station. These are just some non-limiting examples.

[0072] Pre-filled pressurized gas cartridges or cylinders may contain gas at very high pressures, such as 500 psig or higher, e.g., 900 psig or higher, and even up to 2,000-3,000 psig or higher. Accordingly, it may be desirable to direct the flowing pressurized gas from the pressure cylinder or cartridge through a flow restrictor, such as an orifice and / or a pressure regulator to control the gas flow and / or gas pressure before it enters the bottle.

[0073] The pressurized gas is directed into the bottle, and the pressure of the gas forces the liquid medicament from the bottle into the injection device. A feedback mechanism may be provided to indicate when the contents of the bottle have been completely transferred to the injection device, and a vent may vent excess gas to the ambient atmosphere. Because the volume of the pre-filled gas cylinder is small, such as 5 ml or less, or even 2 ml or less, the gas vented to the atmosphere will be relatively insignificant and may not even be noticed by the user.

[0074] After transfer to the injection device is complete, the injection device may be removed from the transfer device and used in the manner previously described in the earlier noted PCT publication WO 2014 / 204894.

[0075] Fig.14 It is a diagrammatic view of a single cylinder transfer system including a pressure vessel in the form of a pre-filled pressurized gas cylinder or barrel 100, a flow restrictor and / or a pressure regulator 101, a liquid medicine bottle 102, and an injection device 103. The cylinder can be any suitable cylinder commercially available or can be a custom cylinder. For example, various possible cylinders can be obtained from Leland Gas Technologies, a company in South Plainfield, New Jersey, USA, which manufactures disposable cylinders filled with high-pressure gas of a capacity from 1 to 1000cc. The cylinder can be filled to a suitable pressure of 2000-3000psig or higher. It is understood that relatively small-capacity disposable cylinders will be suitable for this theme. For example, the cylinder can have a volume that is pressurized to 500psig or higher, such as from 900psig to 2000-3000psig or higher, 10ml or less and more preferably less than 5ml such as 1-2ml.

[0076] The gas may be any suitable gas, such as but not limited to an inert gas. Because it will come into contact with the medicament, the gas is preferably pathogen-free, i.e., free of active pathogens. Nitrogen or argon may be suitable gases. When released from the gas cylinder, such as by puncture by a puncture needle, the gas is directed from the gas cylinder to the bottle 102 through a suitable flow path through the restrictor and / or pressure regulator 101.

[0077] The flow restrictor and / or pressure regulator 101 may be of any suitable construction, preferably small and disposable. A typical flow restrictor may be a diaphragm with a small hole to restrict the flow of gas from the gas cylinder. A pressure regulator may also be included in combination with the flow restrictor or independently of the flow restrictor as desired. From the flow restrictor / regulator, a flow path 104 conducts the gas to the bottle 102.

[0078] The vial 102 may be a standard pharmaceutical vial with a rigid container portion 105, typically glass, open at one end and sealed by a pierceable septum or membrane 106 of latex, silicone or other material. The present process is preferably carried out with the vial in an inverted vertical position so that gas flows to the closed end of the vial, thereby squeezing substantially all of the medicament from the vial under the action of the pressurized gas.

[0079] The flow path 107 directs the medicament from the bottle to a suitable container such as the injection device 103 under gas pressure. The injection device has a medicament reservoir, such as an expandable reservoir for receiving the medicament, for example, a reservoir that expands under pressure from the medicament. When the injection device is actuated by the user, the reservoir can be biased to expel the medicament. In the illustrated embodiment, the injection device 103 has an elastomeric expandable bladder that is initially empty and expands when it is filled with medicament flowing therein under the force or pressure of the gas from the gas cylinder 100. As described in the previously filed PCT application noted above, the elastomeric mass of the bladder biases it to expel the medicament into the subject when later actuated by the user.

[0080] Fig.15 One possible transfer device is generally illustrated at 108 for effecting transfer of liquid medication from a vial 102 to an injection device 103 substantially as described above. The illustrated transfer device has a rigid plastic housing 109 including a vial receiving station 110, shown with the vial 102 inserted, and an injection device receiving station 111, shown with the injection device 103 in place. The housing 109 contains fluid flow paths and various operating mechanisms for effecting transfer of medication from the vial to the injection device.

[0081] This can be Fig.16 is better seen in Fig.15 , but the upper portion of the housing 109 is removed to allow viewing of certain internal components. The fluid flow path may be of any suitable construction such as plastic tubing. Fig.16 Not visible in Fig.16 With the upper portion of the cover removed, the gas cylinder or cartridge 100 can be seen in a pre-fill or pre-start position before the gas is released by the puncture needle 112. In the pre-fill position, the gas cylinder is located between a compression spring, generally shown as component 113, and a pivotable or slidable latch or lever 114 that blocks movement of the gas cylinder toward the puncture needle. Inserting the bottle 102 into the bottle receiving station simultaneously forces one or more access spikes (in Fig.16 106 and depresses latch 114. When latch 114 is depressed, it releases pressurized gas cylinder 100 to move toward puncture needle 112 under the action of compression coil spring 113. This causes the needle to puncture a puncture area or sealing cap on the pressurized gas cylinder and allow compressed gas to flow from the cylinder through the needle. Although spring 113 is described as forcing cylinder 100 toward needle 112, alternatively, the needle can be moved toward the cylinder. Moreover, other types of force generating devices other than coil springs can be utilized.

[0082] Fig.171 is a top view of the lower portion of the housing 109 with the bottle 102 and injection device 103 removed to better illustrate the respective positions of the pressure gas cylinder 100, the compression spring 113 and the latch 114. This position is the position shown when the latch blocks movement of the cylinder and before the pressurized gas cylinder is punctured by the puncture needle 112.

[0083] Fig.18 A possible alternative transfer device is shown with a different arrangement for inserting a bottle 102 to cause puncture of a pressurized gas cylinder 100. The transfer device 115 includes an outer housing 116 with a bottle receiving station 117 and an injection device receiving station 118, with the bottle 102 and injection device 103 shown in their respective stations. In this embodiment, the bottle 102 has an outer shell or sheath 119 that is threaded at one end 120 and includes a radial outer flange 121. The bottle receiving station 117 of the transfer device has internal threads to receive the threaded end of the bottle sheath 119. Insertion and rotation of the bottle sheath 119 forces the access spike 122 through the septum 106 of the bottle. Continued rotation of the bottle sheath causes the radial flange 121 to engage toward a push member 123 positioned on the closed end of the pressurized gas cylinder 100. Upon additional rotation of the bottle sheath, as best in Fig.19 As seen in the figure, the push member 123 pushes the cylinder toward the puncture needle 124, causing it to puncture the sealing cap of the cylinder and allowing gas from the cylinder to pass through a flow channel not shown, through the access spike 122 (or a separate access spike) and flow into the bottle 102 to force the liquid medication from the bottle into the injection device 103. The threaded connection between the transfer device receiving station and the bottle sheath provides a mechanical advantage for puncturing the bottle and the cylinder, which may be beneficial for patients with limited strength or dexterity.

[0084] As in Fig.18 and 19 As shown in , there is a single access spike 122. In this case, the spike will typically include two lumens or flow paths. One lumen will be for the ingress of gas and the other for the egress of liquid medicament. The egress lumen may open adjacent to the inside surface of the diaphragm or at the lowest practical position when the bottle is inverted so that it is below the surface of the medicament and is in a position to expel substantially all of the valuable medicament from the bottle. The gas inlet lumen may lead into the bottle near the distal end of the spike 140 and be separated from the egress lumen by a significant distance so that substantially all of the medicament flows from the bottle before the gas exits. The gas lumen may be configured to open above the height of the medicament (when the bottle is inverted) to enhance liquid transfer and reduce the risk of entrainment of gas in the liquid. Alternatively, the gas inlet and liquid outflow lumens could be contained in separate spikes, particularly where the bottle is pushed into a receiving station. In . Fig.18 and 19In thread forms of 1.5 mm, a single point with two lumens will typically be used.

[0085] Now turn to Fig. 20 . Fig. 20 is similar to Fig.13 Flow chart of the present invention is not provided, but in this case an overview of a dual bottle fluid transfer method and certain exemplary steps of the method is provided, which uses a pressurized gas source to power the transfer of contents such as, for example, diluent from a diluent bottle to a medicament bottle and the combined diluent and medicament from the medicament bottle to an injection device. Alternatively, as previously noted, a pressurized gas source can be used to power the transfer of medicament from a first liquid medicament bottle to a second liquid medicament bottle and the combined medicament from the second bottle to the injection device. Alternatively, one of the bottles can contain a diluent and the other bottle contains a concentrated liquid medicament. Other variations can also be used.

[0086] Fig. 20 Each step in the process may not be required in all embodiments. As reflected in the flow chart, vials containing medicament and vials containing diluent are inserted into the vial receiving station of the transfer device so that separate spikes pierce the vial septum and access the contents of each vial. Each spike may have two lumens, one for gas inlet and the other for diluent or medicament outlet, or two separate spikes may be used for each vial.

[0087] As in the single bottle process, the method is initiated by the user by actuating a gas trigger mechanism that can have a variety of different configurations. As explained, the trigger mechanism can be activated when the bottle is inserted into the bottle receiving station or thereafter. Similar to the single bottle system explained above, the bottle insertion can release a spring force that forces the puncture needle or puncture needle to pass or moves the puncture needle or pressure gas cylinder or both through a sealing diaphragm or cap associated with the pre-filled pressure gas cylinder or cartridge. Alternatively, the user's own force can be used to press the pre-filled gas cylinder and puncture needle together to access the pressurized gas when the bottle is inserted into the receiving station. These are just some non-limiting examples.

[0088] The pre-filled pressurized gas cartridge or cylinder, the gas itself, the flow restrictor and / or the pressure regulator are combined substantially as above Fig.13 As mentioned above, however, the pressurized gas cylinders used in a dual cylinder system may need to have a larger capacity and / or a higher pressure than in a single cylinder system.

[0089] In the double bottle system, pressurized gas is typically first directed to the first bottle such as a bottle containing a liquid medicament or a diluent, and the pressure of the gas forces the liquid medicament or the diluent to enter the second or the medicine bottle from the first bottle. As described in the introduction, the medicament can be a powder or have a lyophilized form, and the injection of the diluent requires resuspension or reconstruction of the medicament. The two bottles can also all contain liquid medicament or diluent and liquid medicament. The force of the pressurized gas also forces the resulting fluid such as resuspension medicament to enter the injection device from the second or the medicine bottle. Feedback mechanism can be set to indicate when the content of the medicine bottle has been fully transferred to the injection device, and the exhaust port can discharge unnecessary gas to the ambient atmosphere. Because the volume of the pre-filled gas cylinder is small, the gas discharged into the atmosphere will be relatively minimal and may even make the user unnoticed. As noted above, each bottle can contain a liquid medicament so that the mixture of these two medicaments such as medicine or "impurities" are pressed into the injection device.

[0090] After transfer to the injection device is complete, the injection device may be removed from the transfer device and used in the manner previously described in the above-identified published PCT application.

[0091] For purposes of illustration and not limitation, Fig.21 is a diagrammatic view of a pressurized gas driven dual bottle resuspension and transfer system including a pressure vessel in the form of a pre-filled pressurized gas bottle or cartridge 200, a flow restrictor and / or pressure regulator 201, a liquid diluent bottle 202D, a medication bottle 202M, and an injection device 203. (Each bottle 202D and 202M can also contain a liquid medication.) As previously explained in connection with the single bottle system, the cylinders may be any suitable cylinders commercially available or may be custom cylinders.

[0092] Also similar to the single bottle system, the gas can be any suitable gas such as but not limited to an inert gas that is preferably pathogen-free, i.e., free of active pathogens. When released, such as by puncture by a puncture needle, the gas is directed from the gas bottle through a restrictor and / or pressure regulator 201 through an appropriate flow path into the diluent bottle 202D.

[0093] The flow restrictor and / or pressure regulator 201 may be of any suitable design that is preferably small and disposable. A typical flow restrictor may be a diaphragm with small holes to restrict the flow of gas from the gas cylinder. A pressure regulator may also be included in combination with the flow restrictor or independently of the flow restrictor as desired. From the flow restrictor / regulator, the flow path 204 conducts the gas to the diluent bottle 202D.

[0094] The diluent (or first liquid medicament) bottle 202D and the medicament (or second liquid medicament) bottle 202M may each be of standard pharmaceutical bottle construction with a rigid container portion 205, typically glass, open at one end and sealed by a pierceable membrane or septum 206 of latex, silicone or other material. The present process is preferably carried out with the bottle in an inverted vertical position so that gas flows to the closed end of the bottle, thereby squeezing substantially all of the diluent and / or medicament from the bottle under the force of the pressurized gas before any gas leaves the medicament bottle.

[0095] From the diluent (or first liquid medicament) bottle 202D, flow path 207D directs the diluent (or liquid medicament) under the pressure of the gas into the medicament bottle 202M, where it can resuspend the medicament if it is in dry lyophilized form, or dilute the medicament if it is in liquid concentrate form (or simply combine or mix with the medicament if it is in liquid non-concentrated form). From the medicament bottle 202M, the combined medicament and diluent or the diluted or mixed liquid medicament flows under the pressure of the gas through flow path 207M to any suitable container, such as the injection device 203 disclosed in the previously noted PCT application. As noted above, the injection device can have an expandable reservoir for receiving the medicament, such as an elastomeric bladder.

[0096] Fig. 22 One possible transfer device is generally illustrated at 208 for effecting transfer of liquid diluent or medicament from vial 202D to vial 202M and from vial 202M to injection device 203. The illustrated transfer device has a rigid plastic housing 209 including a dual vial receiving station 210 shown with vials 202D and 202M inserted and an injection device receiving station 211 shown with injection device 203 in place. The housing contains fluid flow paths and operating mechanisms for effecting transfer of diluent or medicament and resulting medicament from the vial to the injection device.

[0097] This is Fig.23 This can be better seen in the figure, which is similar to Fig. 22 , but the upper portion of the housing 209 is removed to allow viewing of certain internal components. The fluid flow path may have a suitable configuration such as plastic tubing. Fig.23 Not visible in Fig.23 With some portion of the cover removed, the gas cylinder or cartridge 200 can be seen in a position prior to the release of gas by the puncture needle 212. In this position, the gas cylinder is located between a compression spring, generally seen as component 213, and a pivotable or slidable latch or lever 214 that normally blocks movement of the gas cylinder toward the puncture needle.

[0098] Inserting bottle pair 202D and 202M into bottle receiving station 210 simultaneously forces one or more access spikes (at Fig.23 214. When the latch 214 is depressed, it moves to an unblocked position, thereby releasing the pressurized gas cylinder 200 to move toward the puncture needle 212 under the force of the compressed coil spring 213, which causes the needle to puncture the puncture area or sealing cap on the pressurized gas cylinder and allow compressed gas to flow from the cylinder. Although the cylinder is described as being forced toward the spike using a spring, alternatively, the spike can be moved toward the cylinder and other types of force generating devices other than coil springs can be used. Both the spike and the cylinder can be moved toward each other by the same or different force generating devices, as desired.

[0099] Fig.24 2 is a top view of the lower portion of the housing 214 with bottles 202D and 202M and injection device 203 removed to better illustrate the respective positions of the pressure cylinder 200, spring 213 and latch 214. This position is shown when the latch blocks movement of the cylinder and before the pressurized gas cylinder is punctured by the puncture needle 212.

[0100] Fig.25 is a cross-sectional view of a system 230 for resuspending dry or micro-agglomerated material stored in a container such as bottle 231 . Fig.25 The components of the system shown are exemplary only and may be varied as will be apparent after reading this specification. In the illustrated embodiment, the system generally comprises a housing at 232 having a bottle receiving station 233, a diluent receiving port 234, a gas connection port 235 and an exhaust port 226.

[0101] The illustrated bottle receiving station 233 has two puncture spikes 227 and 228 for passing through the septum of bottle 231. When inverted in the vertical position, spike 227 extends substantially into the bottle so as to open near the bottom of the bottle and be separated from the bottle septum. Spike 228 is shorter and opens into the bottle at a position adjacent to the inside surface of the septum. Each spike has an inner cavity. The inner cavity of spike 227 is communicated with exhaust port 226 via a pipeline or other flow path in outer cover 232. The inner cavity of spike 228 is communicated with flow path 229, which extends between the spike and one port on 3-way valve 230. Flow path 231 extends between another port on the 3-way valve and diluent port 234, and flow path 232 extends between the third port on the three-way valve and gas port 235. Alternatively, a single puncture spike with a dual lumen can also be used.

[0102] In the illustrated system, a syringe 233 is coupled to the diluent port 234. The syringe can provide a source of diluent for resuspension of the microaggregates in the bottle and a means for later extracting the suspension from the bottle. In addition, a filter 234 is coupled to the exhaust port 226. As will be described below, the filter may take any suitable form and is preferably hydrophobic to prevent leakage of liquid into the environment.

[0103] In operation, a bottle 231 containing a dry material such as a medicament in the form of microaggregates is first connected to a bottle receiving station 233. A syringe 233 containing a diluent is connected to a diluent port 234, and a source of pressurized gas (not shown) is connected to a gas port 235. A three-way valve is set to allow the diluent to flow from the flow path 231 to the fluid flow path 229 leading to the spike 228. The diluent is injected from the syringe into the bottle. The valve 230 is then turned so that the gas can flow from the gas port 235 through the channel 229 to the spike 228. The spike 228 opens toward the bottle below the height of the diluent and the bubbling gas entering the bottle causes agitation between the diluent and the microaggregate material. The gas rises to the bottom of the inverted bottle and leaves through the inner cavity of the spike 227. In the event that the gas carries any liquid with it, a hydrophobic filter 234 in the exhaust flow path prevents the liquid from leaking while allowing the gas to continue to discharge.

[0104] The introduction of gas into the bottle continues for a selected period of time until the microaggregates are substantially completely suspended in the diluent due to agitation by the incoming gas. The 3-way valve is then returned to a position where the diluent flow path 231 and the flow path 229 are connected, and the syringe 233 is retracted to extract the suspended microaggregates from the bottle. The filter 234 allows replacement air to be discharged into the bottle, and the position of the spike 228 allows substantially all of the microaggregates to be extracted from the bottle. Using this system, the microaggregates can be reliably and predictably resuspended without worrying about the uncertainty and variability that can occur when manual resuspension is used.

[0105] Additional aspects and variations

[0106] Without limiting anything in the foregoing or appended claims, other general and more specific aspects and variations of the subject matter of the present specification are set forth below.

[0107] Aspect 1 is a method of transferring a fluid from a bottle containing the fluid to an injection device, comprising: introducing a pressurized gas into the bottle; causing the fluid to flow from the bottle under pressure from the gas; and causing the fluid to flow from the bottle to the injection device under the action of the pressurized gas.

[0108] Aspect 2 is the method of Aspect 1, wherein the fluid is a diluent and the pressurized gas flows into a bottle containing the diluent, and under pressure from the pressurized gas, the diluent flows from the bottle containing the diluent into a bottle containing the medicament and the combined diluent and medicament flows from the bottle containing the medicament into the injection device.

[0109] Aspect 3 is the method of aspect 1, wherein the bottle is a first bottle containing a first liquid medicament, and under the action of pressurized gas, the first medicament flows from the first bottle to a second bottle containing a second liquid medicament, and the mixed first and second medicaments flow from the second bottle to the injection device.

[0110] Aspect 4 is the method of aspect 1, 2 or 3, wherein the injection device comprises an expandable reservoir, and the fluid or the combined diluent and medicament or the mixed first and second medicaments flows into the expandable reservoir under pressure from the pressurized gas.

[0111] Aspect 5 is the method of aspect 3, wherein the expandable reservoir comprises an elastomeric bladder.

[0112] Aspect 6 is the method of aspect 3 or 4, wherein the reservoir is biased to expel the fluid or the combined diluent and medicament or the mixed first and second medicaments.

[0113] Aspect 7 is the method of any of aspects 1-6, wherein the pressurized gas flows from a pre-filled pressure vessel.

[0114] Aspect 8 is the method of aspect 7, wherein the container comprises a pierceable seal and the method comprises piercing the seal.

[0115] Aspect 9 is the method of any of aspects 1-8, wherein the gas is substantially free of pathogens.

[0116] Aspect 10 is the method of any one of aspects 1-9, comprising filtering the gas before it enters the bottle.

[0117] Aspect 11 is the method of any one of aspects 7-10, wherein the pressure container is a gas-filled cylinder having a volume of 10 ml or less.

[0118] Aspect 12 is the method of aspect 11, wherein the cartridge has a volume of approximately 1 ml or less.

[0119] Aspect 13 is the method of any of aspects 7-12, wherein the pressure vessel initially contains a gas at a pressure greater than about 500 psig.

[0120] Aspect 14 is the method of any one of aspects 1-13, wherein the gas is an inert gas.

[0121] Aspect 15 is the method of any one of aspects 1-14, wherein the gas is selected from the group consisting of nitrogen, helium, neon, argon, krypton, and xenon.

[0122] Aspect 16 is the method of any of aspects 4-16, comprising removing entrained gas from the fluid before the fluid enters the expandable accumulator.

[0123] Aspect 17 is the method of any of aspects 1-16, wherein the pressurized gas flows from a pre-filled cartridge having a volume of about 1 ml or less and a pressure of about 900 psig or more.

[0124] Aspect 18 is the method of any one of aspects 1-17, comprising controlling the flow rate and / or pressure of the gas.

[0125] Aspect 19 is a drug transfer apparatus for transferring a fluid from a bottle containing the fluid to an injection device, comprising a pressurized gas source, at least one bottle receiving station, and a drug injection device receiving station, a gas flow path capable of communicating between the gas source and the bottle receiving station, and a fluid flow path capable of communicating between the bottle receiving station and the drug injection device receiving station.

[0126] Aspect 20 is the drug transfer device of Aspect 19, wherein the transfer device includes at least a first bottle receiving station and a second bottle receiving station, and a gas flow path is capable of communicating between a pressurized gas source and the first bottle receiving station and a fluid flow path is capable of communicating between the first bottle receiving station and the second bottle receiving station and between the second bottle or the final receiving station and the injection device.

[0127] Aspect 21 is the medicament transfer device of aspect 19 or 20, wherein the source of pressurized gas comprises a pre-filled pressure container.

[0128] Aspect 22 is the medicament transfer device of aspect 21, wherein the container comprises a pierceable seal and the device comprises a piercing needle for piercing the seal.

[0129] Aspect 23 is the medicament transfer device of aspect 21, comprising an actuator for moving the puncture needle and / or the pressure container between the pre-puncture position and the puncture position.

[0130] Aspect 24 is the medicament transfer device of aspect 22, wherein the actuator comprises an energy storage source biased to move the puncture needle and / or the pressure container to the puncture position.

[0131] Aspect 25 is the medicament transfer device of aspect 23, wherein the energy storage device includes a spring.

[0132] Aspect 26 is the medicament transfer device of aspect 21, wherein the puncture needle includes a seal for contacting the pressure container to limit leakage of the pressurized gas into the surrounding environment.

[0133] Aspect 27 is the medicament transfer device of any of aspects 19-26, wherein the pressurized gas is substantially free of pathogens.

[0134] Aspect 28 is the medicament transfer device of any of aspects 19-27, wherein the gas flow path comprises a filter for filtering the gas before the gas enters the bottle.

[0135] Aspect 29 is the medicament transfer device of any of aspects 19-28, wherein the pressurized gas source is a pre-filled gas cartridge having a volume of 10 ml or less.

[0136] Aspect 30 is the medicament transfer device of any of aspects 19-29, wherein the pressurized gas source has a volume of approximately 1 ml or less.

[0137] Aspect 31 is the medicament transfer device of any of aspects 19-30, wherein the pressure source initially comprises a gas at a pressure greater than about 500 psig.

[0138] Aspect 32 is the medicament transfer apparatus of any one of aspects 19-31, wherein the gas is an inert gas.

[0139] Aspect 33 is the medicament transfer apparatus of any one of aspects 19-31, wherein the gas is selected from the group consisting of nitrogen, helium, neon, argon, krypton, and xenon.

[0140] Aspect 34 is the medicament transfer device of any of aspects 19-32, wherein the fluid flow path comprises a gas collector for removing entrained gas from the fluid prior to entering the injection device.

[0141] Aspect 35 is the medicament transfer device of any of aspects 19-32, wherein the pressurized gas source is a pre-filled cartridge having a volume of about 1 ml or less and a pressure of about 900 psig or more.

[0142] Aspect 36 is the medicament transfer device of any one of aspects 19-35, comprising a flow regulator and / or a pressure regulator for controlling the flow and / or pressure of the gas from the pressurized gas source.

[0143] Aspect 37 is the medicament transfer apparatus of any one of aspects 19-36, comprising a medicament injection device received in an injection device receiving station.

[0144] Aspect 38 is the medicament transfer device of aspect 37, wherein the injection means comprises a reservoir capable of expanding under the pressure of a fluid flowing under the action of a pressurized gas or a combined diluent and medicament or a mixed medicament.

[0145] Aspect 39 is the medicament transfer device of aspect 38, wherein the expandable reservoir comprises an elastomeric bladder.

[0146] Aspect 40 is the medicament transfer device of aspect 38 or 39, wherein the expandable reservoir is biased to expel fluid or a combined diluent and medicament or a mixed medicament when expanded.

[0147] Aspect 41 is a resuspension device for resuspending the contents of a medicament of a bottle of the type having an open end sealed by a septum, the resuspension device comprising an outer cover, the outer cover comprising: a diluent port; a gas port; an exhaust port; a bottle receiving station; a first pointed inner cavity and a second pointed inner cavity extending from the bottle receiving station to puncture the bottle septum when the bottle is received at the bottle receiving station; a gas flow path connected between the air inlet port and the first pointed inner cavity; a diluent flow path connected between the diluent port and the first pointed inner cavity; an exhaust flow path connected between the exhaust port and the second pointed inner cavity; and a hydrophobic filter cooperatively associated with the exhaust flow path to filter gas passing through the exhaust flow path and substantially prevent liquid from leaking from the exhaust flow path.

[0148] Aspect 42 is the resuspension device of aspect 41, comprising a flow node between the gas flow path and the diluent flow path upstream of the first pointed inner cavity, and a valve associated with the flow node to control the flow of gas and / or diluent between the first pointed inner cavity and the gas port and the first pointed inner cavity and the diluent port, respectively.

[0149] Aspect 43 is the resuspension device of aspect 41 or 42, wherein the first tip lumen and the second tip lumen are defined in a single puncture tip.

[0150] Aspect 44 is the resuspension device of aspect 41, wherein the first tip lumen is defined in a first puncture tip and the second tip lumen is defined in a separate second puncture tip.

[0151] Aspect 45 is the resuspension device of any one of aspects 41-44, wherein the second spike-shaped lumen has a greater length than the first spike-shaped lumen so as to extend further into a bottle received at the receiving station.

[0152] Aspect 46 is the resuspension device of any one of Aspects 41-45, wherein the first pointed lumen is configured to open into the bottle so as to be below the level of the diluent during resuspension and the second pointed lumen is configured to open into the bottle at a position so as to be above the level of the diluent during resuspension.

[0153] Aspect 47 is the resuspension device of any one of aspects 41-46, wherein the first pointed lumen is configured to open into the vial at a location proximal to the septum and the second pointed lumen is configured to open into the vial at a location substantially spaced from the septum.

[0154] Aspect 48 is a method of resuspending the contents of a pharmaceutical dose in a bottle, the method comprising: introducing a diluent into the bottle; injecting a gas under pressure into the bottle at a height below the diluent in the bottle to cause agitation of the diluent; exhausting the gas from the bottle; and continuing the injection and exhaust until the medicinal contents are substantially resuspended.

[0155] Aspect 49 is the resuspension method of aspect 48, comprising substantially preventing leakage of liquid with the discharged gas.

[0156] Aspect 50 is the resuspension method of aspect 48 or 49, wherein the exhausted gas passes through a hydrophobic filter to substantially prevent leakage of liquid from the bottle.

[0157] Aspect 51 is the method of any of aspects 48-50, wherein the gas is discharged from the bottle at a height above the height of the diluent.

[0158] Aspect 52 is the method of any one of aspects 48-51, wherein the pharmaceutical contents of the vial are in a substantially dry state.

[0159] Aspect 53 is the method of any one of aspects 48-52, wherein the dosage contents of the vial comprise lyophilized material.

[0160] Aspect 54 is the method of any of aspects 48-53, wherein the gas is substantially free of pathogens.

[0161] Although the subject matter has been described with reference to the illustrated examples and various aspects and variations, this is intended to be illustrative rather than limiting. It should be understood that the subject matter may be applied or modified in other situations without departing from the disclosure herein.

Claims

1. A method of transferring a fluid from a bottle containing the fluid to an injection device, comprising: puncturing a pressurized gas cylinder by inserting the fluid-containing bottle into a transfer device, wherein the transfer device has a rigid plastic housing, the housing including a bottle receiving station and an injection device receiving station, the bottle receiving station having a spike for puncturing a bottle septum and accessing the contents of the fluid-containing bottle; introducing pressurized gas from the punctured pressurized gas cylinder into the fluid-containing bottle; causing fluid to flow from the fluid-containing bottle under pressure from the gas; causing the fluid to flow from the fluid-containing bottle into the injection device under the force of the pressurized gas, wherein, in the housing and in the pre-filled position, the latch blocks the release of the spring force of the spring towards the puncture needle, and wherein inserting the fluid-containing bottle into the bottle receiving station of the transfer device forces the spike to penetrate the bottle septum and depress the latch, thereby releasing the spring force of the spring which forces the puncture needle to penetrate the sealing septum associated with the pressurized gas cylinder, thereby puncturing the pressurized gas cylinder.

2. The drug transfer method according to claim 1, comprising: A medicament is combined with the fluid after causing the fluid to flow from the fluid-containing bottle and before causing the fluid to flow into an injection device.

3. The drug transfer method according to claim 2, wherein the combining step comprises: causing the fluid to flow from the vial containing the fluid to a second vial containing the medicament under pressure from the gas, and The step of causing the fluid to flow into the injection device comprises causing the combined fluid and medicament to flow from the second bottle into the injection device under the force of the pressurized gas.

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