Systems, methods, and apparatus for drug injection devices

Abstract

The present disclosure relates to systems and devices for administering an active agent to a subject. The provided apparatus comprises: a housing; an elastic release member; the outer cap can be jointed with the elastic release piece in a separable manner and can rotate along with the elastic release piece; a diluent pusher, wherein the diluent pusher comprises a stopper; a hybrid elastic member adjacent to the diluent pusher, thereby providing a bias pressure to the diluent pusher within the housing; the powder barrel comprises a first puncturable sealing element and a second puncturable sealing element; and a crown member positioned adjacent to the second pierceable seal, and configured to pierce the second pierceable seal in response to translation of the powder cartridge within the housing toward the proximal end; and a fluid chamber disposed between the stopper and the first pierceable seal. Methods of producing active agents are also described.

Description

[0001] Cross - Reference to Related Applications

[0002] This application claims priority and the benefit of U.S. Provisional Application No. 63 / 384,385, filed on November 18, 2022, entitled "SYSTEMS, METHODS, AND APPARATUSES FOR DRUG INJECTORS", the entire content of which is incorporated herein by reference. Technical Field

[0003] The present disclosure relates to a device that includes a needle for administering an active agent to a subject, wherein the active agent is in solid form in a chamber that is isolated from a diluent or pharmaceutically acceptable carrier located in another chamber, and the device is capable of exposing the active agent to the diluent or pharmaceutically acceptable carrier for reconstitution, mixing, or dissolution prior to administering the active agent. Background Art

[0004] For a long time, emergency injections have been used to address various forms of extremely urgent and life - threatening events, including drug overdose, allergic reactions, angioedema, or adrenal insufficiency (AI). Due to the urgent need and importance of the active ingredient, drug delivery requires both precision and speed. In fact, while certain naloxone auto - injection devices and epinephrine - containing auto - injection devices provide more user - friendly and administrable drug delivery systems, steroid injection devices, despite being equally important, are still plagued by cumbersome delivery systems due to their reliance on reconstitution, resulting in sub - optimal drug delivery devices in terms of drug preparation and delivery.

[0005] For example, some prior designs require an individual to inject bacteriostatic water or bacteriostatic saline solution into a sterile vial containing dry hydrocortisone powder, where the diluent in the upper vial is connected to the lower vial containing the active dry hydrocortisone ingredient. This requires laborious manipulation of completely different or connected vials within a critically short period of time to mix, withdraw, and administer the reconstituted mixture. Even in the case of relatively simple and similar drug - mixing systems, users on average require twelve steps or more to complete an injection. Thus, there is a need for a simplified reconstitution device. Summary of the Invention

[0006] The present disclosure relates to systems, methods, and devices for delivering, storing, reconstituting, and injecting active pharmaceutical agents, and the present disclosure provides solutions to the problems identified above.

[0007] One aspect of the present disclosure provides an injection device for delivering a solution of an active agent and a diluent to a subject. The injection device includes a housing. The injection device includes an elastic release member. The injection device includes an outer cap that is separably engageable with the elastic release member and rotatable with the elastic release member. The injection device includes a diluent ejector that includes a stopper. The injection device includes a mixing elastic member adjacent to the diluent ejector to provide a biasing force to the diluent ejector within the housing. The injection device includes a powder cylinder that includes a first tearable seal and a second tearable seal. The injection device includes a crown of thorns positioned near the second tearable seal and configured to pierce the second tearable seal in response to proximal translation of the powder cylinder within the housing. The injection device includes a fluid chamber disposed between the stopper and the first tearable seal.

[0008] Another aspect of the present disclosure provides a method of administering an active agent to a subject through an injection device. The method includes: twisting the outer cap of the injection device to initiate mixing of the active agent and the diluent. The method of initiating mixing includes: actuating the elastic release member to release the mixing elastic member such that the mixing elastic member provides an axial force to the diluent ejector, causing the diluent ejector to translate proximally through the injection device. The method of initiating mixing includes: using the diluent ejector to pierce the first tearable seal and provide an axial force to the powder cylinder such that the diluent ejector and the powder cylinder translate proximally through the injection device toward the crown of thorns. The method of initiating mixing includes: piercing, via the crown of thorns, a second tearable seal positioned near the diluent ejector and the powder cylinder, thereby causing the active agent and the diluent to begin mixing into an at least partially mixed solution. The method of initiating mixing includes: transferring, via the force from the mixing elastic member, the at least partially mixed solution between the crown of thorns and toward a mixing chamber seal, wherein the force of the at least partially mixed solution passing through the crown of thorns causes the mixing chamber seal to translate proximally and form a mixing chamber in which the active agent and the diluent are completely mixed into a fully mixed solution.

[0009] Another aspect of the present disclosure provides a method of assembling an injection device. The method includes: inserting a powder cartridge containing an active pharmaceutical agent into a syringe barrel. The method includes: adding a diluent to the syringe barrel. The method includes inserting a diluent pusher into the syringe barrel such that the diluent is positioned between the diluent pusher and the powder cartridge, thereby creating a sterile-sealed subassembly of the diluent and the active pharmaceutical agent.

[0010] These and other aspects of the invention will be described in the following detailed description and the accompanying drawings. For those of ordinary skill in the art, other aspects and features of the examples of the invention will become apparent when reviewing the following description of specific exemplary examples of the invention in conjunction with the accompanying drawings. Although the features of the invention may be discussed in connection with certain examples and drawings, all examples of the invention may include one or more of the features discussed herein. Additionally, although one or more examples may be described as having certain advantageous features, one or more of these features may also be used with the various examples of the invention discussed herein. In a similar manner, although the exemplary examples may be discussed below as device examples, system examples, or method examples, it should be understood that such exemplary examples may be implemented in various devices, systems, and methods of the invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] The drawings incorporated in and forming a part of this specification illustrate several examples of the disclosed subject matter and are used to explain the principles of the disclosed subject matter. The drawings are not intended to limit the scope of the disclosed subject matter in any way. In the drawings:

[0012] Figure 1 is a side cross-sectional view of an injection device in accordance with an aspect of the present disclosure.

[0013] Figure 2A and Figure 2B is a view of an inner syringe barrel (see Figure 2A ) and a diluent pusher and powder cartridge (see Figure 2B ) in accordance with an aspect of the present disclosure.

[0014] Figure 2C is a cross-sectional view of the distal end of an assembled syringe barrel in accordance with an aspect of the present disclosure.

[0015] Figure 3 is a schematic cross-sectional view showing a crown piece in accordance with an aspect of the present disclosure.

[0016] Figure 4A shows a latch of an injection device in accordance with an aspect of the present disclosure.

[0017] Figure 4BShows a latch inserted into a syringe barrel according to aspects of the present disclosure.

[0018] Figure 5 Shows the insertion of a needle member and a needle hub into a syringe barrel according to aspects of the present disclosure.

[0019] Figure 6A Shows the assembly of a needle cap onto a syringe barrel according to aspects of the present disclosure. Figure 6B Is a detailed view of the proximal end of a needle cap according to aspects of the present disclosure.

[0020] Figure 7A Shows the assembly of a needle cap onto a syringe barrel according to aspects of the present disclosure. Figure 7B Is a detailed view of a track for a needle cap according to aspects of the present disclosure.

[0021] Figure 8A Is a detailed view of two powder barrels according to aspects of the present disclosure, with the bottom barrel showing a cross-sectional view of the powder barrel. Figure 8B Shows the assembly of a powder barrel within a syringe barrel according to aspects of the present disclosure.

[0022] Figure 9 Shows the addition of a diluent to Figure 8B the syringe barrel shown in

[0023] Figure 10A Shows a disassembled diluent injection device and its corresponding stopper according to aspects of the present disclosure. Figure 10B Shows the placement of Figure 10A the diluent injection device and its corresponding stopper in Figure 9 the syringe barrel shown in

[0024] Figure 11 Shows the assembly of a diluent pusher and its corresponding stopper into Figure 10B the syringe barrel of

[0025] Figure 12 Shows an elastic container and an elastic release member according to aspects of the present disclosure.

[0026] Figure 13A Is a detailed view of an elastic container engaged with an elastic release member; Figure 13B Is a front view of an elastic container engaged with an elastic release member according to aspects of the present invention.

[0027] Figure 14 Shows the insertion of Figure 13B the elastic release member of Figure 11 into the partially assembled injection device shown in

[0028] Figure 15 shows the addition of a hybrid elastomer to the Figure 14 injection device shown in

[0029] Figure 16 is a perspective view of the distal end of an injection device according to aspects of the present disclosure, which shows the addition of a hybrid elastomer to the end of the injection device and shows the release ring of an elastomeric release member engaged with an elastomeric container.

[0030] Figure 17A is the Figure 15 insertion of the hybrid elastomer into the distal end of a syringe barrel; Figure 17B is a side view of an injection device according to aspects of the present invention, which shows the addition of a fixing clamp to the hybrid elastomer to cover the hybrid elastomer.

[0031] Figure 18 is a cross-sectional view of the distal end of an injection device after the addition of the Figure 17B fixing clamp according to aspects of the present disclosure.

[0032] Figure 19 is a side elevation view of a housing and an outer cap according to aspects of the present disclosure.

[0033] Figure 20 shows the insertion of the Figure 18 assembled syringe barrel according to aspects of the present disclosure into the Figure 19 housing.

[0034] Figure 21 is a side elevation view of an assembled injection device according to aspects of the present disclosure.

[0035] Figures 22A to 22C shows actuation of the injection device by rotating the outer cap according to aspects of the present disclosure. Figure 22A shows the injection device in an initial state; Figure 22B shows the injection device with the outer cap twisted to initiate reconstitution; and Figure 22C shows the injection device with the outer cap removed.

[0036] Figure 23A and Figure 23B are partial transparent views of an injection device according to aspects of the present disclosure. Figure 23A shows the outer cap on the syringe, and Figure 23B shows the outer cap removed so that the injection device is ready for injection.

[0037] Figures 24A to 24CIs a cross-sectional view of a mixing chamber according to an aspect of the present disclosure, and these views show the process of the latch being released from the engaged state with the needle hub to deliver the reconstituted active pharmaceutical agent. Figure 24A Shows the position of the latch during reconstitution; Figure 24B Shows the process of the latch being released from the needle hub and advancing distally during injection; and Figure 24C Shows the latch at the end of injection.

[0038] Figure 25A And Figure 25B Shows the needle cap locking feature according to an aspect of the present disclosure. Figure 25A Shows the barrel pin located in the rest slot (before injection), and Figure 25B Shows the barrel pin located in the locking slot (after injection).

[0039] Figure 26A And Figure 26B Shows an alternative design for the injection device according to an aspect of the present disclosure. Figure 26A Shows a syringe barrel having only a single distal stop and no powder barrel. Figure 26B Shows a device having no powder barrel or corresponding powder barrel stop and only a first pierceable seal and a second pierceable seal.

[0040] Figure 27 Is a flowchart showing a method of administering an active pharmaceutical agent to a subject by an injection device according to an aspect of the present disclosure.

[0041] Figure 28 Is a flowchart showing at least a part of a method of assembling an injection device according to an aspect of the present disclosure.

[0042] Figure 29 Is a flowchart showing at least a part of a method of assembling an injection device according to an aspect of the present disclosure.

[0043] Figure 30 Is a flowchart showing at least a part of a method of assembling an injection device according to an aspect of the present disclosure.

[0044] Figure 31 Is a flowchart showing a method of manufacturing an active pharmaceutical agent according to an aspect of the present disclosure.

[0045] Figure 32 Is a table showing the results of testing spray-dried sodium hydrocortisone succinate prepared by the method using Figure 31

[0046] Figure 33 Is a table showing exemplary spray-drying conditions for sodium hydrocortisone succinate according to an aspect of the present disclosure. Detailed Embodiments

[0047] Specific examples of the present invention will now be described in detail with reference to the accompanying drawings, where like reference numerals represent functionally similar or identical elements. These examples provide solutions for drug injection devices and injection device systems that are simplified, user-friendly, and safe. The described injection devices and injection device systems include reconstitution devices that enable one-step activation and reconstitution. The active pharmaceutical agent is stored separately from the diluent, and mixing can be accomplished by moving the diluent pusher proximally within the system. The features of the injection devices described herein may also include locking features to prevent accidental reuse of a used device.

[0048] Now refer to Figure 1 , which provides an exemplary cross-sectional view of an injection device 100 according to aspects of the present disclosure. The features of the injection device 100 can be discussed in terms of the process of activating the device. The injection device 100 can be activated by twisting the outer cap 202 relative to the outer housing 200. The twisting can initiate the mixing of the active pharmaceutical agent 404 and the diluent 402, thereby "reconstituting" the active pharmaceutical agent 404. The outer cap 202 can engage an elastic release member 102 located at the distal end of the outer cap 202, and twisting (or rotation) of the outer cap 202 can cause the elastic release member 102 to also rotate within the housing 200. It should be clarified that when "proximal" or "distal" are mentioned in the present disclosure, it will be understood from the perspective of a person self-administering an injection using the injection device 100. For example, the part of the injection device 100 closest to the person is "proximal", and the part farthest from the person is "distal". In Figure 1 , thus, the right-hand side of the figure is "proximal" because that is the direction of the skin of the person self-administering the injection.

[0049] Now referring again to the elastic release member 102, actuation of the elastic release member 102 can cause the mixing elastic member 104 to be released and the diluent pusher 106 to move proximally through the injection device 100. As can be seen from Figure 1 , the mixing elastic member 104 can be located within an elastic container 105, and the elastic container 105 can be releasably engaged with the elastic release member 102 (e.g., via a cam 232 of the elastic release member 102 engaging a groove 220 in the elastic container 105; see Figure 16 and Figure 18 ). The diluent pusher 106 can include a stop 107. The injection device 100 can also include a powder cylinder 108 that houses the active pharmaceutical agent 404. The powder cylinder 108 can include a proximal stop 110 and a distal stop 112. The proximal stop 110 and the distal stop 112, in their engagement with the syringe barrel 208 (see, for example, Figure 2A) provide a liquid-tight seal therebetween such that fluid must pass through the powder cartridge 108. The distal stop 112 may include a first pierceable seal 116, and the proximal stop 110 may include a second pierceable seal 114. The active agent 404 is contained between the first pierceable seal 116 and the second pierceable seal 114. A fluid chamber 302 is defined between the first pierceable seal 116 and the stop 107 of the diluent pusher 106, and the diluent 402 is contained in the fluid chamber 302. The pierceable seals 114, 116 may be foil materials, such as metal foil materials, as foil is easily pierced during operation of the device. Other pierceable materials are also contemplated.

[0050] When the mixing spring 104 releases its compressive force to bias the diluent pusher 106 to drive the pusher proximally, the proximal tip of the diluent pusher 106 will penetrate the first pierceable seal 116. At this time, the diluent 402 in the fluid chamber 302 may flow proximally and into the powder cartridge 108. The positive pressure generated in the fluid chamber 302 due to the fluid and the diluent pusher 106 moving proximally causes the powder cartridge 108 to also move proximally and toward the ratchet crown 118. Then, the ratchet crown 118 will pierce the second pierceable seal 116, and the diluent 402 and the partially redissolved active agent 404 will flow through the powder cartridge 108, through the ratchet crown 118, and toward the mixing chamber seal 122. The mixing chamber seal 122 provides a liquid-tight seal between it and the syringe barrel 208 (see, for example Figure 2A ) such that fluid cannot pass proximally through the mixing chamber seal 122 unless the seal is pierced (as defined below and shown in more detail in Figures 24A to 24C ).

[0051] As the pressure and diluent pusher 106 continuously moves the fluid proximally, the mixing chamber seal 122 will be pushed proximally, and during this process, the mixing chamber seal 122 will move to form the mixing chamber 120, enabling the active pharmaceutical agent 404 to be fully redissolved in the mixing chamber 120. The proximal movement of the mixing chamber seal 122 causes the injection elastomer 134 to collapse under positive pressure. The mixing chamber seal 122 also includes a latch 136 extending therefrom, and the latch 136 is positioned to engage with the needle hub 126 proximal to the latch 136. The needle cap seal 130 seals the area between the needle hub 126 and the needle cap 128. The needle 124 is fixed within the needle hub 126, and when the mixing chamber seal 122 moves proximally, the needle 124 does not translate within the injection device 100. Thus, when the mixing chamber seal 122 moves proximally, the distal end of the needle 124 will pierce the mixing chamber seal 122. When the mixing chamber seal 122 moves proximally far enough, the latch 136 will engage and connect with the needle hub 126. Once the latch 136 engages with the needle hub 126, the mixing chamber 120 can be considered fully formed, enabling the active pharmaceutical agent 404 to be fully redissolved. After redissolution, the injection device 100 is ready for injection.

[0052] The outer cap 202 (see Figure 23B ) can be removed, and the proximal end 132 of the needle cap 128 can be placed on the patient's skin. The proximal end 132 of the needle cap 128 can include a needle stop seal 138, and the needle 124 can pierce the needle stop seal 138. As shown, when the injection device 100 is in the un-fired configuration, the needle 124 can rest within the needle stop seal 138. Then, the operator of the injection device 100 can move the housing 200 towards the skin, at which time the needle cap 128 will move distally relative to the housing 200, thereby withdrawing the distal end of the needle 124. The platform 139 at the distal end of the needle cap 128 can disengage the latch 136 from the needle hub 126 to initiate the injection process. The injection elastomer 134 decompresses, and positive pressure is again generated within the mixing chamber 120, and this pressure can be relieved by the redissolved active pharmaceutical agent 404 flowing into the distal end of the needle 124, through the needle 124, and into the patient's body.

[0053] Once the redissolved active pharmaceutical agent 404 has been administered, the user of the injection device 100 can retract the needle from the patient's skin, and the needle 124 can be reinserted into the needle cap 128. To this end, the needle cap elastomer 140 can expand and force the proximal end 132 of the needle cap 128 to re-sheath the needle 124. As will be described in more detail in Figure 25A and Figure 25B , a locking mechanism can be provided to ensure that the used injection device 100 cannot be reused.

[0054] Figure 2A and Figure 2B are views of syringe inner barrel 208 (see Figure 2A ), diluent pusher 106, and powder barrel 108 (see Figure 2B ) according to aspects of the present disclosure. In Figure 2A , syringe inner barrel 208 is transparent to show the positions of, for example, mixing chamber seal 122, injection elastomer 134, needle cap seal 130, and needle cap elastomer 140. Syringe inner barrel 208 can be positioned within housing 200 (see Figure 1 ), and this feature forms fluid channels for diluent 402 and active agent 404. The distal end of syringe inner barrel 208 (i.e., Figure 2A 's top) can include barrel lip 209, which can interact with fixed clamp 222 (see Figure 18 ). Figure 2B shows diluent pusher 106 and its corresponding stop 107, and powder barrel 108 and its corresponding proximal stop 110 and distal stop 112. Figure 2C is a cross-sectional view of the distal end of assembled syringe barrel 208 according to aspects of the present disclosure. This view shows the positions of diluent pusher 106, the corresponding chambers (i.e., fluid chamber 302, powder chamber 304, and mixing chamber 120), and additional features of assembled, un-fired syringe barrel 208 as described herein.

[0055] Figure 3 is a schematic cross-sectional view showing crown member 118 according to aspects of the present disclosure. In any embodiment, crown member 118 has a sharp end at the distal end to pierce or puncture second pierceable seal 114 when powder barrel 108 is translated proximally. As can be seen from Figure 3 , in one example, crown member 118 can include one or more protrusions 119A that extend from within syringe barrel 208. These protrusions can extend from the material of syringe barrel 208 and toward second pierceable seal 114. Between protrusions 119A is fluid channel 119B, which enables at least a portion of the reconstituted active agent 404 from powder barrel 108 to pass through and enter mixing chamber 120. However, it should be understood that crown member 118 as described in the present disclosure can be a single protrusion that pierces or punctures second pierceable seal 114, and there are no limitations on crown member 118, which looks like Figure 3 's serrated feature shown. In other words, the term "crown member" is not intended to imply a limitation to look like Figure 3Rather than the fully annular structure shown, it is only intended to show that one or more protrusions extend distally from the position of the crown member to pierce or puncture the second pierceable seal 114.

[0056] Figure 4A Latch 136 extending from the mixing chamber seal 122 is shown. Figure 4B Latch 136 and mixing chamber seal 122 inserted into syringe barrel 208 are shown. Figure 5 After latch 136 and mixing chamber seal 122 have been inserted, needle member 124, needle hub 126, and injection elastomer 134 are added to syringe barrel 208, as shown.

[0057] Figure 6A Needle cap 128 being added to Figure 5 the partially assembled syringe barrel 208; and Figure 6B A detailed view of needle stop seal 138 at the proximal end 132 of needle cap 128 is shown. Needle cap 128 can slide downward until one or more barrel pins 210 on syringe barrel 208 slide into track 212 in needle cap 128. Figure 7A Needle cap 128 mounted on syringe barrel 208 with one or more barrel pins 210 inserted into stationary slots 214 is shown. Thus, needle cap 128 may also include a platform 139 extending distally. More details regarding the locking mechanism provided by track 212 will be described in conjunction with Figure 25A and Figure 25B herein.

[0058] Figure 8A A detailed view of two powder barrels 108 according to aspects of the present disclosure is shown, with the bottom powder barrel 108 showing a cross-sectional view. Figure 8B Powder barrel 108 assembled within syringe barrel 208 (such as Figure 7A syringe barrel 208 in Figure 9 ) is shown. As shown in

[0059] Figure 10A An unassembled diluent pusher 106 and its corresponding stopper 107 are shown. Stopper 107 may be made of an elastic material to form a liquid-tight seal around the moving diluent pusher 106 such that the diluent pusher 106 pushes the diluent proximally as it moves proximally. In Figure 10BIn it, the diluent pusher 106 and its corresponding stopper 107 are inserted into the syringe barrel 208 to form a fluid chamber (see Figure 1 ), and the diluent is sealed therein. Figure 11 The injection device after the diluent pusher 106 and its corresponding stopper 107 have been inserted is shown.

[0060] Figures 12 to 18 Details of the elastic release member 102 mechanism described above are highlighted respectively. Now refer to Figure 12 , the elastic container 105 can be engaged with the elastic release member 102 (for details on how to arrange the release ring 228 to engage with the elastic container 105, see Figure 16 ). The elastic container 105 can be open at one end (the distal end) and closed at the other end. Figure 13A The engagement of (i) the cam 232 of the elastic release member 102 and (ii) the groove 220 on the elastic container 105 is shown. As Figure 14 shown, once the elastic container 105 is engaged with the elastic release member 102, the combination of these two components can be assembled onto the partially assembled injection device 100 (e.g., the partially assembled injection device shown in Figure 11 ). As described above, the open end of the elastic container 105 can point distally so that the mixing elastic member 104 can be inserted into the open end, as shown in Figure 15 .

[0061] Figure 16 The distal end of the injection device 100 is shown, where the mixing elastic member 104 has been inserted and the release ring 228 is engaged with the groove 220 of the elastic container 105. It will be noted that the view in Figure 16 is a partial cross-section, so the most distal parts of the elastic container 105 and the mixing elastic member 104 have been removed to more easily show the engagement of the groove 220. The release ring 228 can include one or more elastic arms 230. Figure 16 The example shown in Figure 1)。The outward deflection of the resilient arm 230 can be actuated by the torsion mechanism of the resilient release member 102. As described above, once the hybrid resilient member 104 is released to drive the diluent pusher 106, reconstitution can begin, and the torsion of the outer cap 202 will in turn twist the resilient release member 102, causing the resilient arm 230 to deflect outwardly. It will also be understood that the amount of "twist" required to initiate mixing can be adjusted by how much the resilient release member 102 needs to be moved to rotate and deflect the resilient arm 230. For example, the injection device 100 can be configured such that the outer cap 202 (and thus the resilient release member 102) must be twisted between 0° and 20° before the resilient arm 230 has moved along the lever extension 226 far enough to release the resilient container 102. This can be manipulated such that twisting the outer cap 202 includes twisting the outer cap 202 relative to the housing 200 between 0° and 45° before the cam 232 disengages from the groove 220; such that twisting the outer cap 202 includes twisting the outer cap 202 relative to the housing 200 between 0° and 90° before the cam 232 disengages from the groove 220; such that twisting the outer cap 202 includes twisting the outer cap 202 relative to the housing 200 between 0° and 135° before the cam 232 disengages from the groove 220; such that twisting the outer cap 202 includes twisting the outer cap 202 relative to the housing 200 between 0° and 180° before the cam 232 disengages from the groove 220; such that twisting the outer cap 202 includes twisting the outer cap 202 relative to the housing 200 between 0° and 225° before the cam 232 disengages from the groove 220; such that twisting the outer cap 202 includes twisting the outer cap 202 relative to the housing 200 between 0° and 270° before the cam 232 disengages from the groove 220; such that twisting the outer cap 202 includes twisting the outer cap 202 relative to the housing 200 between 0° and 315° before the cam 232 disengages from the groove 220; such that twisting the outer cap 202 includes twisting the outer cap 202 relative to the housing 200 between 0° and 360° before the cam 232 disengages from the groove 220; or such that twisting the outer cap 202 includes twisting the outer cap 202 relative to the housing 200 by more than 360° before the cam 232 disengages from the groove 220.

[0062] Each resilient arm 230 can be deflected by a feature that acts as an inclined plane within the injection device 100. In some examples, the inclined plane can be, for example, a lever extension extending from the distal end of the syringe barrel 208. In other examples, and as Figure 16 shown, the inclined plane can be a lever extension 226 extending from the fixed clamp 222 (see also Figure 18 ). Now referring to Figure 17A , this view shows the hybrid resilient member 104 inserted into the resilient container 105 before the hybrid resilient member 104 is compressed. In Figure 17BIn [the figure], the fixed clamp 222 can be inserted into the distal end of the injection device 100 to compress and accommodate the mixing elastic member 104. As shown, the fixed clamp 222 can include a connecting extension 224 extending therefrom, and the connecting extension 224 can engage with the barrel lip 209 to keep the mixing elastic member 104 in a compressed state. Figure 18 is a cross-sectional view of the distal end of the injection device 100 after the fixed clamp 222 in accordance with aspects of the present disclosure is added. This figure provides a detailed view of the engagement of the connecting extension 224 with the barrel lip 209. Here, the cam 232 also extends into the groove 220, and the rotation of the elastic release member 102 causes the elastic arm 230 to travel along the lever extension 226 and deflect outwardly. Figure 17B

[0063] Figures 19 to 20 Shows the final assembly step of the injection device. Figure 19 is a side elevation view of the housing 200 and the outer cap 202 in accordance with aspects of the present disclosure. The housing 200 and the outer cap 202 can be combined before inserting the assembled syringe barrel 208. Figure 20 Shows inserting the Figure 18 assembled syringe barrel 208 of Figure 19 into the housing 200 of Figure 21 is a side elevation view of the assembled injection device 100 in accordance with aspects of the present disclosure. Figures 19 to 20 Also provided is a view of the optional windows in the housing 200, which can provide visual information related to the reconstitution state. The housing 200 can include a powder inspection window 204, which is disposed near the position of the powder barrel 108. The powder inspection window 204 can provide an observation of the powder barrel 108 before or during the first mixing of the active agent and the diluent. For example, the position of the powder inspection window 204 can be such that the active agent 404 in the powder barrel 108 can be seen before reconstitution, and once the diluent pusher 106 pierces the first pierceable seal 116, the powder inspection window 204 can show that the initial piercing has occurred. The housing 200 can also include a reconstitution window 206, which is disposed within the wall of the housing 200, near the position of the ratchet crown 118 (i.e., near the mixing chamber 120). The reconstitution window 206 can provide an observation of the position near the final mixing of the active agent 404 and the diluent 402 within the injection device 100. The windows 204, 206 can be made of a translucent plastic material, or the windows 204, 206 can simply be openings in the wall of the housing 200.

[0064] Figures 22A to 22C Shows rotating the outer cap 202 to initiate reconstitution in accordance with aspects of the present disclosure. Figure 22A Shows the injection device 100 in its initial state. Figure 22BAn injection device 100 is shown in which the outer cap 202 is twisted such that the mixing resilient member 104 is actuated, as described above. Figure 22C An injection device 100 is shown with the outer cap 202 removed. Figure 23A and Figure 23B are partial transparent views of the injection device 100 provided by twisting and removing the outer cap 202.

[0065] Figures 24A to 24C is a cross-sectional view of the mixing chamber 120 and this view provides details of the process of releasing the latch 136 from its engaged state with the needle hub 126 to deliver the reconstituted active agent 404 through the needle member 124. As can be seen from Figure 24A at this point the injection device 100 is ready and prepared for injection. The needle member 124 has now extended to the distal end of the mixing chamber seal 122 and thus, by moving the mixing chamber seal 122 distally again, the reconstituted active agent 404 can be delivered through the needle member. To release the latch 136 from the needle hub 126, a platform 129 on the needle cap 128 (see Figure 6B ) can contact the proximal end portion of the latch 136 extending through the needle hub 126. This causes the latch 136 to disengage and the injection resilient member 134 pushes the mixing chamber seal 122 distally, thereby pushing the fluid out of the needle member 124. The injection device can include some feedback mechanisms during this delivery process. For example, when the latch 136 disengages from the needle hub 126, the initial contact between the platform 129 and the latch 136 can provide audible and / or tactile feedback. In Figure 24B the mixing chamber seal 122 is pushed distally, thereby expelling more fluid. Another feedback mechanism can occur or be initiated at the end of the injection. The needle hub 126 can include a needle hub extension 234 extending distally, the needle hub extension 234 including an extension ramp 236. The latch 136 can include a latch ramp 238 which can engage with the extension ramp 236. For example, when the latch 136 is pushed distally by the mixing chamber seal 122, the extension ramp 236 can abut against the latch ramp 238, thereby providing audible and / or tactile feedback indicating that the liquid injection is about to be completed. In Figure 24C the injection has been completed.

[0066] Figure 25A and Figure 25B show the locking features of the needle cap 128 according to aspects of the present disclosure. Figure 25A shows the barrel pin 210 located in the rest slot 214, which is the configuration the injection device 100 may be in before injection. When an injection is performed and the needle cap 128 is pressed against the skin while the housing 200 moves proximally, the barrel pin 210 will travel along the track 212 after passing the deflector plate 218. After injection, the needle cap resilient member 140 (seeFigure 1 )Push the needle cap 128 back to cover the needle 124, and at this time, the barrel pin 210 will travel backward through the track 212. The barrel pin 210 will contact the deflector 218, and the deflector 218 will rotate the needle cap 128 so that the barrel pin 210 travels into the locking groove 216. In Figure 25B , the barrel pin 210 is located in the locking groove 216, and the needle 124 remains covered so that the used device cannot be inadvertently reused.

[0067] Figure 26A and Figure 26B shows an alternative design for the injection device 100 in accordance with aspects of the present disclosure. Figure 26A shows a syringe barrel 208 having only a single distal stop 112 and no powder barrel 108. In this example, there is no powder barrel to define the powder chamber 304, which is the same as the situation in the example shown in Figure 1 . In the example shown in Figure 26A , the powder chamber 304 is defined at one end by the distal stop 112 including the first pierceable seal 116 and at the other end by the mixing chamber seal 122 (which slides distally when in the stationary, un-fired position in the figure). The fluid channel 119B can extend between the powder chamber 304 and the mixing chamber seal 122. In some examples, the syringe barrel 208 can have a narrow section 306 around the powder chamber 304. In this example, when the diluent pusher 106 fires proximally, the proximal tip of the diluent pusher 106 will pierce the first pierceable seal 116. At this time, the diluent 402 in the fluid chamber 302 can flow proximally and into the powder chamber 304. The positive pressure generated in the powder chamber 304 causes the mixing chamber seal 122 to move proximally due to the fluid moving proximally through the fluid channel 119B. In this way, the mixing chamber 120 will be formed, and the reconstitution process can proceed as in the other examples summarized above.

[0068] Figure 26BThe syringe barrel 208 is shown without the powder barrel 108 and without any corresponding stop between the diluent pusher 106 and the mixing chamber seal 122. In this example, the powder chamber 304 is defined at one end by the first pierceable seal 116 and at the other end by the second pierceable seal 114. The fluid passage 119B may extend between the second pierceable seal 114 and the mixing chamber seal 122. In some examples, the syringe barrel 208 may have a constricted section 306 around the powder chamber 304. In this example, when the diluent pusher 106 is fired proximally, the proximal tip of the diluent pusher 106 will pierce the first pierceable seal 116. At this time, the diluent 402 in the fluid chamber 302 may flow proximally and into the powder chamber 304. The positive pressure generated in the powder chamber 304, due to the fluid moving proximally into the powder chamber 304, causes the second pierceable seal 114 to be pierced. Then, at least a portion of the reconstituted active agent 404 will flow through the fluid passage 119B and cause the mixing chamber seal 122 to move proximally. In this way, the mixing chamber 120 will be formed, and the reconstitution process can proceed as in the other examples outlined above. In some alternative examples, Figure 26B the device shown in Figure 26A may not include the second pierceable seal 114, similar to the device shown in

[0069] Figure 27is a flowchart showing a method 2700 of administering an active agent to a subject by an injection device 100 in accordance with aspects of the present disclosure. The method 2700 may include actuating 2705 an elastic release member 102 to release a mixing elastic member 104 such that the mixing elastic member 104 provides an axial force onto a diluent pusher 106, causing the diluent pusher 106 to translate proximally through the injection device 100. The method 2700 may include piercing 2710 a first pierceable seal 116 with the diluent pusher 106 and providing an axial force on a powder cartridge 108 such that the diluent pusher 106 and the powder cartridge 108 translate proximally through the injection device 100 toward a crown member 118. The method 2700 may include piercing 2715 a second pierceable seal 114 positioned proximal to the diluent pusher 106 and the powder cartridge 108 via the crown member 118, causing the active agent 404 and the diluent 402 to begin mixing into at least a partially mixed solution. The method 2700 may include passing 2720 the at least partially mixed solution through spaces between the crown members 118 and toward a mixing chamber seal 122 via a force from the mixing elastic member 104, wherein the force passing the at least partially mixed solution through the crown members 118 causes the mixing chamber seal 122 to translate proximally and form a mixing chamber in which the active agent 404 and the diluent 402 are completely mixed into a fully mixed solution (402 + 404). The method 2700 may end after step 2720 or additional steps may be performed in accordance with the embodiments described herein.

[0070] Figure 28 is a flowchart showing at least a portion of a method 2800 of assembling an injection device 100 in accordance with aspects of the present disclosure. The method 2800 may include inserting 2805 a powder cartridge 108 containing an active agent 404 into a syringe barrel 208. The method 2800 may include adding 2810 a diluent 402 to the syringe barrel 208. The method 2800 may include inserting 2815 a diluent pusher 106 into the syringe barrel 208 such that the diluent is positioned between the diluent pusher 106 and the powder cartridge 108, thereby creating a sterile sealed subassembly for the diluent 402 and the active agent 404. The method 2800 may end after the insertion step 2815 or additional steps may be performed in accordance with the embodiments described herein. For example, in addition to those steps described for Figure 28 those described, these steps described in Figure 28 may also be performed.

[0071] Figure 29is a flow chart showing at least a part of a method 2900 of assembling an injection device 100 according to aspects of the present disclosure. The method 2900 may include covering 2905 a syringe barrel 208 with an elastic container 105 including an elastic release member 102. The method 2900 may include covering 2910 the elastic container 105 with a fixing jig 222 including a mixing elastic member 104. The method 2900 may include inserting 2915 the syringe barrel 208 and the elastic container 105 into a housing 200. The method 2900 may end after the insertion step 2915, or additional steps may be performed according to the embodiments described herein. For example, in addition to those steps described for Figure 28 and / or Figure 29 the steps described for Figure 30 may also be performed.

[0072] Figure 30 is a flow chart showing at least a part of a method 3000 of assembling an injection device 100 according to aspects of the present disclosure. The method 3000 may include connecting 3005 a mixing chamber seal 122 to a latch 136. The method 3000 may include inserting 3010 the mixing chamber seal 122 and the latch 136 into the syringe barrel 208. The method 3000 may include inserting 3015 a needle member 124 and an injection elastic member 134 into the syringe barrel 208. The method 3000 may include at least partially covering 3020 the syringe barrel 208 with a needle cap 128. The method 3000 may end after the covering step 3020, or additional steps may be performed according to the embodiments described herein.

[0073] In any of the examples described herein, the injection device 100 may deliver, for example, sodium succinate hydrocortisone, hydrocortisone phosphate, and / or hydrocortisone acetate. However, it should be understood that other active agents may also be included. In some examples, the active agent may be spray-dried or lyophilized, and the spray-dried or lyophilized product may be provided in a powder barrel 108. In certain examples, spray-dried sodium succinate hydrocortisone has many advantages. Spray drying can be a simple, single process from solution to powder, while lyophilization requires additional grinding or micronization. Spray drying provides consistent particle size and flow properties, and the particle size distribution can be adjusted by particle engineering as needed. Accordingly, the present disclosure also provides a solution for spray-drying sodium succinate hydrocortisone for placement in the powder barrel 108.

[0074] Figure 31is a flow chart showing a method 3100 of manufacturing an active pharmaceutical agent (e.g., active pharmaceutical agent 404) according to aspects of the present disclosure. Method 3100 may include adding 3105 approximately 1.95 g of hydrocortisone 21 - hemisuccinate API to 50 mL of acetone and stirring until a completely dissolved solution is obtained. Method 3100 may include adding 3110 approximately 100 mL of WFI to the completely dissolved solution. Method 3100 may include adding 3115 approximately 0.1 normal concentration of NaOH while stirring until a resulting solution with a pH value of 7.4 is obtained. Method 3100 may include heating 3120 the resulting solution to 25 °C using a rotary evaporator under vacuum to remove acetone, thereby leaving a final solution with a volume of approximately 50 mL. Method 300 may include adding 3125 approximately 12.2 mg of anhydrous sodium dihydrogen phosphate and approximately 133 mg of disodium hydrogen phosphate to the final solution and stirring until dissolved. Method 3000 may include adjusting 3130 the pH value of the final solution to 7.4. Method 3100 may end after the adjustment step 3130, or additional steps may be performed in a manner described or understood herein.

[0075] Perform the steps outlined above to identify the purity obtained using such a method 3100, and the data is provided in the table shown in Figure 32 The spray - dried powder tested (labeled "Existing HSS" in the table) was analyzed using RP - HPLC, and its purity / impurity profile was compared with that of the API (hydrocortisone hemisuccinate) and the results measured for the RLD (Solu - Cortef TM ) in the same chromatographic system. The data (area %) and the relevant United States Pharmacopeia (USP) specifications are as shown in Figure 32 as follows.

[0076] Compared with the feed API, "Existing HSS" showed an increase in the content of hydrocortisone (hydrolysis product), and an unknown impurity appeared at RRT 0.57. The impurities observed at RRT 1.13 and RRT 1.53 are from the API and are not a concern as the supplied API is GMP - grade and suitable for human use. The USP specifications for hydrocortisone hemisuccinate require that the content of any single impurity does not exceed 1%, and the total impurity content does not exceed 2%. This API meets these specifications.

[0077] USP also has relevant specifications for hydrocortisone sodium succinate injection. This specification allows the free hydrocortisone content not to exceed 6.7%. However, this specification does not clearly stipulate the impurity content in the HSS injection formulation. In summary, "Existing HSS" meets the purity specification requirements.

[0078] The final solution can be spray-dried. Spray-drying the therapeutic agent can be understood to mean placing the therapeutic agent at a high temperature and then cooling it, thereby producing an evaporation process. In this example, the final solution of HSS can be spray-dried according to Figure 33 the parameters shown therein. For example, the spray-drying conditions for HSS are: the inlet temperature is from 82 °C to 150 °C, and the outlet temperature is from 50 °C to 90 °C; for example, the inlet temperature is from 147 °C to 150 °C, and the outlet temperature is 90 °C; the inlet temperature is 111 °C, and the outlet temperature is 70 °C; the inlet temperature is from 95 °C to 99 °C, and the outlet temperature is 60 °C; the inlet temperature is 82 °C, and the outlet temperature is 50 °C, etc. (see Figure 33 ). The active pharmaceutical agent can be spray-dried using nitrogen.

[0079] The examples of the present disclosure can be implemented according to at least the following clauses:

[0080] Clause 1: An injection device for delivering a solution of an active pharmaceutical agent and a diluent to a subject, the injection device comprising: a housing (200); an elastic release member (102); an outer cap (202) that is detachably engaged with the elastic release member (102) and is rotatable with the elastic release member (102); a diluent pusher (106) that includes a stopper (107); a mixing elastic member (104) that is adjacent to the diluent pusher (106) to provide a bias for the diluent pusher (106) within the housing (200); a powder cylinder (108) that includes a first pierceable seal (116) and a second pierceable seal (114); a ratchet crown member (118) that is positioned near the second pierceable seal (114) and is configured to pierce the second pierceable seal (114) in response to proximal translation of the powder cylinder (108) within the housing (200); and a fluid chamber (302) that is disposed between the stopper (107) and the first pierceable seal.

[0081] Clause 2: The injection device according to Clause 1, further comprising a mixing chamber seal (122) that is movable within the housing (200) in response to a positive pressure caused by proximal translation of the diluent pusher (106) via the mixing elastic member (104).

[0082] Clause 3: The injection device according to Clause 2, wherein the injection device further comprises: a latch (136) connected to the mixing chamber seal (122); and a needle hub (126) capable of engaging with the latch (136).

[0083] Clause 4: The injection device according to Clause 2 or 3, wherein the injection device further comprises: a needle (124); a needle cap (128); and a needle cap elastic member (140).

[0084] Clause 5: The injection device according to Clause 2, wherein the outer cap (202) can be twisted between 0° and 20° by the elastic release member (102).

[0085] Clause 6: The injection device according to Clause 2, wherein the outer cap (202) can be twisted between 0° and 45° by the elastic release member (102).

[0086] Clause 7: The injection device according to Clause 2, wherein the outer cap (202) can be twisted between 0° and 90° by the elastic release member (102).

[0087] Clause 8: The injection device according to Clause 2, wherein the outer cap (202) can be twisted between 0° and 135° by the elastic release member (102).

[0088] Clause 9: The injection device according to Clause 2, wherein the outer cap (202) can be twisted between 0° and 180° by the elastic release member (102).

[0089] Clause 10: The injection device according to Clause 2, wherein the outer cap (202) can be twisted between 0° and 225° by the elastic release member (102).

[0090] Clause 11: The injection device according to Clause 2, wherein the outer cap (202) can be twisted between 0° and 270° by the elastic release member (102).

[0091] Clause 12: The injection device according to Clause 2, wherein the outer cap (202) can be twisted between 0° and 315° by the elastic release member (102).

[0092] Clause 13: The injection device according to Clause 2, wherein the outer cap (202) can be twisted between 0° and 360° by the elastic release member (102).

[0093] Clause 14: The injection device according to Clause 2, wherein twisting the outer cap (202) includes twisting the outer cap (202) by more than 360°.

[0094] Clause 15: The injection device according to any one of Clauses 2 to 14, the injection device further comprising an active pharmaceutical agent (404), the active pharmaceutical agent (404) being provided within the powder cylinder (108).

[0095] Clause 16: The injection device according to Clause 15, wherein the active pharmaceutical agent (404) is a spray-dried powder stored in the powder cylinder (108).

[0096] Clause 17: The injection device according to Clause 16, wherein the active pharmaceutical agent (404) is sodium hydrocortisone succinate.

[0097] Clause 18: The injection device according to Clause 16, wherein the powder cylinder (108) contains more than 75 mg of spray-dried powder.

[0098] Clause 19: The injection device according to any one of the preceding clauses, wherein the outer cap (202) is capable of engaging with the housing (200) to cover and protect the needle cap (128).

[0099] Clause 20: The injection device according to any one of the preceding clauses, wherein the cross-section of the housing (200) is in the shape of a teardrop.

[0100] Clause 21: The injection device according to any one of the preceding clauses, wherein the housing (200) includes a powder inspection window (204), the powder inspection window (204) being provided near the location of the powder cylinder (108).

[0101] Clause 22: The injection device according to any one of the preceding clauses, wherein the housing (200) includes a powder inspection window (204), the powder inspection window (204) being provided near the location of the powder cylinder (108), the powder inspection window (204) providing an observation of the powder cylinder (108) before or during the first mixing of the active pharmaceutical agent and the diluent.

[0102] Clause 23: The injection device according to any one of the preceding clauses, wherein the housing (200) includes a reconstitution window (206), the reconstitution window (206) being provided within the wall of the housing (200) and near the ratchet crown (118), the reconstitution window (206) providing an observation of the final mixing location of the active pharmaceutical agent and the diluent within the injection device.

[0103] Clause 24: The injection device according to Clause 23, wherein the housing (200) further includes a powder inspection window (204), the powder inspection window (204) is disposed near the position of the powder cylinder (108), and the powder inspection window (204) provides an observation of the powder cylinder (108) before or during the first mixing of the active pharmaceutical agent and the diluent.

[0104] Clause 25: The injection device according to any one of the preceding clauses, the injection device further includes an elastic container (105), the elastic container (105) is close to the diluent pusher (106) and engages with the mixing elastic member (104), the elastic container (105) and the elastic release member (102) can be releasably engaged, wherein detaching the elastic container (105) from the elastic release member (102) releases the biasing force on the elastic container (105) to actuate the diluent pusher (106).

[0105] Clause 26: The injection device according to Clause 25, wherein: the elastic container (105) includes a circumferential groove (220); the elastic release member (102) includes an elastic arm (230), wherein a cam (232) extends from the elastic arm, the cam (232) extends into the circumferential groove (220); and the elastic arm (230) is configured to deflect radially to disengage the cam (232) from the circumferential groove (220).

[0106] Clause 27: The injection device according to Clause 26, the injection device further includes a fixed clamp (222), the fixed clamp engages with the housing (200) at the distal end of the mixing elastic member (104), the fixed clamp (222) includes a lever extension (226), the lever extension (226) extends proximally and extends into the housing (200).

[0107] Clause 28: The injection device according to Clause 27, wherein the lever extension (226) is positioned near the elastic arm (230) and the lever extension (226) can engage with the elastic arm (230), wherein the elastic arm (230) is configured to engage with the lever extension (226) in response to the rotation of the elastic release member (102), thereby causing the elastic arm (230) to deflect radially.

[0108] Clause 29: A method of administering an active agent to a subject through an injection device, the method comprising: twisting an outer cap of the injection device to initiate mixing of the active agent and a diluent, the initiation of mixing comprising the steps of: actuating an elastic release member to release a mixing elastic member such that the mixing elastic member provides an axial force to a diluent pusher, thereby causing the diluent pusher to translate proximally through the injection device; using the diluent pusher to pierce a first pierceable seal and provide an axial force to a powder cylinder such that the diluent pusher and the powder cylinder translate proximally through the injection device towards a crown member; piercing, via the crown member, a second pierceable seal positioned proximal to the diluent pusher and the powder cylinder, thereby causing the active agent and the diluent to begin to mix into at least a partially mixed solution; and transferring, via a force from the mixing elastic member, the at least partially mixed solution between the crown members and towards a mixing chamber seal, wherein the force of the at least partially mixed solution passing through the crown member causes the mixing chamber seal to translate proximally and form a mixing chamber in which the active agent and the diluent are completely mixed into a fully mixed solution.

[0109] Clause 30: The method according to Clause 29, the method further comprising priming the fully mixed solution for injection, wherein priming comprises the steps of: in response to the proximal translation of the mixing chamber seal, piercing the mixing chamber seal with a needle member; and translating, via a force from the mixing elastic member acting on the active agent and the diluent, a latch fixed to the mixing chamber seal proximally towards a needle seat, wherein the proximal translation of the mixing chamber seal and the latch loads an injection elastic member.

[0110] Clause 31: The method according to Clause 30, wherein priming further comprises the step of deflecting the latch such that the latch engages a deflecting member to fix the needle seat, thereby holding the injection elastic member in a compressed position.

[0111] Clause 32: The method according to Clause 30 or 31, the method further comprising: removing the outer cap from the injection device; and injecting the fully mixed solution, the injection comprising the steps of: placing a proximal end of the needle cap at the skin of the subject and moving the housing of the injection device proximally such that the needle cap translates distally relative to the housing and independently of the needle member such that a proximal end of the needle member exits the needle cap proximally; in response to the distal translation of the needle cap, causing the needle seat to translate distally within the injection device to create a pressure in the fully mixed solution between the needle seat and the diluent pusher; and delivering the fully mixed solution through the needle member by the pressure.

[0112] Clause 33: The method according to Clause 32, the method further comprising: removing the needle from the skin by pulling the injection device away from the subject; and causing the needle to be covered by the needle cap via the needle cap elastic member.

[0113] Clause 34: The method according to Clause 33, the method further comprising permanently covering the needle with the needle cap via the needle cap elastic member.

[0114] Clause 35: The method according to any one of Clauses 32 to 34, wherein delivering the fully mixed solution comprises delivering about 1 mL of the fully mixed solution.

[0115] Clause 36: The method according to any one of Clauses 32 to 35, wherein delivering the fully mixed solution comprises delivering less than 1 mL of the fully mixed solution.

[0116] Clause 37: The method according to any one of Clauses 32 to 36, wherein delivering the fully mixed solution comprises delivering about 2 mL of the fully mixed solution.

[0117] Clause 38: The method according to any one of Clauses 32 to 37, wherein delivering the fully mixed solution comprises delivering less than 2 mL of the fully mixed solution.

[0118] Clause 39: The method according to any one of Clauses 32 to 38, wherein delivering the fully mixed solution comprises delivering more than 2 mL of the fully mixed solution.

[0119] Clause 40: The method according to any one of Clauses 32 to 39, wherein delivering the fully mixed solution can be accomplished at any angle relative to the horizontal direction.

[0120] Clause 41: The method according to any one of Clauses 29 to 40, wherein the active pharmaceutical agent is a spray-dried powder stored in the powder cylinder.

[0121] Clause 42: The method according to Clause 41, wherein the active pharmaceutical agent is sodium hydrocortisone succinate.

[0122] Clause 43: The method according to Clause 41 or 42, wherein the powder cylinder comprises more than 75 mg of spray-dried powder.

[0123] Clause 44: The method according to any one of Clauses 29 to 43, wherein twisting the outer cap includes twisting the outer cap relative to the housing by between 0° and 20°.

[0124] Clause 45: The method according to any one of Clauses 29 to 43, wherein twisting the outer cap includes twisting the outer cap relative to the housing by between 0° and 45°.

[0125] Clause 46: The method according to any one of Clauses 29 to 43, wherein twisting the outer cap includes twisting the outer cap relative to the housing by between 0° and 90°.

[0126] Clause 47: The method according to any one of Clauses 29 to 43, wherein twisting the outer cap includes twisting the outer cap relative to the housing by between 0° and 135°.

[0127] Clause 48: The method according to any one of Clauses 29 to 43, wherein twisting the outer cap includes twisting the outer cap relative to the housing by between 0° and 180°.

[0128] Clause 49: The method according to any one of Clauses 29 to 43, wherein twisting the outer cap includes twisting the outer cap relative to the housing by between 0° and 225°.

[0129] Clause 50: The method according to any one of Clauses 29 to 43, wherein twisting the outer cap includes twisting the outer cap relative to the housing by between 0° and 270°.

[0130] Clause 51: The method according to any one of Clauses 29 to 43, wherein twisting the outer cap includes twisting the outer cap relative to the housing by between 0° and 315°.

[0131] Clause 52: The method according to any one of Clauses 29 to 43, wherein twisting the outer cap includes twisting the outer cap relative to the housing by between 0° and 360°.

[0132] Clause 53: The method according to any one of Clauses 29 to 43, wherein twisting the outer cap includes twisting the outer cap relative to the housing by more than 360°.

[0133] Clause 54: The method according to any one of Clauses 29 to 52, wherein the active agent and the diluent are automatically and completely mixed in the mixing chamber within less than or equal to 20 seconds.

[0134] Clause 55: The method according to Clause 32, the method further includes providing an audible cue when the fully mixed solution is completely delivered through the needle.

[0135] Clause 56: A method of assembling an injection device, the method comprising: inserting a powder cartridge containing an active pharmaceutical agent into a syringe barrel; adding a diluent to the syringe barrel; and inserting a diluent pusher into the syringe barrel such that the diluent is positioned between the diluent pusher and the powder cartridge, thereby creating a sterile-sealed sub-assembly of the diluent and the active pharmaceutical agent.

[0136] Clause 57: The method according to Clause 56, the method further comprising: covering the syringe barrel with an elastic container including an elastic release member; covering the elastic container with a mixing elastic member and a fixing clamp; and inserting the syringe barrel and the elastic container into a housing.

[0137] Clause 58: The method of Clause 56 or 57 further comprises: connecting a mixing chamber seal to a latch; inserting the mixing chamber seal and the latch into the syringe barrel; inserting a needle member and an injection elastic member into the syringe barrel; and at least partially covering the syringe barrel with a needle cap.

[0138] Clause 59: The method according to any one of Clauses 56 to 58, the method further comprising manufacturing the active pharmaceutical agent, wherein producing the active pharmaceutical agent comprises: adding about 1.95 g of hydrocortisone 21 - hemisuccinate API to 50 mL of acetone and stirring until a completely dissolved solution is obtained; adding about 100 mL of WFI to the completely dissolved solution; adding about 0.1 normal concentration of NaOH while stirring until a resulting solution with a pH value of 7.4 is obtained; heating the resulting solution to 25°C using a rotary evaporator under vacuum to remove acetone, thereby leaving a final solution with a volume of about 50 mL; adding about 12.2 mg of anhydrous sodium dihydrogen phosphate and about 133 mg of disodium hydrogen phosphate to the final solution and stirring until dissolved; and adjusting the pH value of the final solution to 7.4.

[0139] Clause 60: The method according to Clause 59, wherein the step of manufacturing the active pharmaceutical agent further comprises spray drying the final solution using nitrogen.

[0140] Clause 61: The method according to Clause 60, the method further comprising spray drying the final solution at an inlet temperature of 82°C to 150°C and an outlet temperature of 50°C to 90°C.

[0141] Clause 62: A method of manufacturing an active pharmaceutical agent, the method comprising:

[0142] About 1.95 g of hydrocortisone 21 - hemisuccinate API was added to 50 mL of acetone and stirred until a completely dissolved solution was obtained;

[0143] About 100 mL of WFI was added to the completely dissolved solution;

[0144] About 0.1 normal concentration of NaOH was added while stirring until a resulting solution with a pH value of 7.4 was obtained;

[0145] The resulting solution was heated to 25 °C using a rotary evaporator under vacuum to remove acetone, leaving a final solution with a volume of approximately 50 mL;

[0146] About 12.2 mg of anhydrous sodium dihydrogen phosphate and about 133 mg of disodium hydrogen phosphate were added to the final solution and stirred until dissolved; and

[0147] The pH value of the final solution was adjusted to 7.4.

[0148] Clause 63: The method according to Clause 62, wherein the step of manufacturing the active pharmaceutical further comprises spray - drying the final solution with nitrogen.

[0149] Clause 64: The method according to Clause 62 or 63, the method further comprising spray - drying the final solution under conditions where the inlet temperature is 82 °C to 150 °C and the outlet temperature is 50 °C to 90 °C.

[0150] Clause 65: An injection device for delivering a solution of an active pharmaceutical and a diluent to a subject, the injection device comprising:

[0151] A housing;

[0152] An elastic release member;

[0153] An outer cap that is separably engageable with and rotatable with the elastic release member;

[0154] A diluent pusher that includes a stopper;

[0155] A mixing elastic member that is adjacent to the diluent pusher to provide a biasing force for the diluent pusher within the housing;

[0156] A mixing chamber seal;

[0157] A fluid chamber that is close to the stopper;

[0158] A powder chamber; and

[0159] A first pierceable seal, the first pierceable seal being positioned between the fluid chamber and the powder chamber.

[0160] Clause 66: The injection device according to Clause 65, wherein the diluent pusher is configured to translate proximally and at least partially pierce the first pierceable seal, so that the diluent contained in the fluid chamber enters the powder chamber and the diluent is mixed with the active pharmaceutical agent positioned in the powder chamber.

[0161] Clause 67: The injection device according to Clause 65, wherein the first pierceable seal is at least partially disposed within a stopper.

[0162] Clause 68: The injection device according to Clause 65, the injection device further comprising a second pierceable seal, the second pierceable seal being positioned between the powder chamber and the mixing chamber seal.

[0163] Clause 69: The injection device according to Clause 68, the injection device further comprising a fluid passage disposed between the second pierceable seal and the mixing chamber seal.

[0164] Clause 70: The injection device according to Clause 65, the injection device further comprising:

[0165] A latch, the latch being connected to the mixing chamber seal; and

[0166] A needle hub, the needle hub being engageable with the latch.

[0167] Clause 71: The injection device according to Clause 65, the injection device further comprising:

[0168] A needle-like member;

[0169] A needle cap; and

[0170] A needle cap elastic member.

[0171] Clause 72: The injection device according to Clause 65, wherein the outer cap is capable of twisting between 0° and 20° via the elastic release member.

[0172] Clause 73: The injection device according to Clause 65, wherein the outer cap is capable of twisting between 0° and 45° via the elastic release member.

[0173] Clause 74: The injection device according to Clause 65, wherein the outer cap is capable of twisting between 0° and 90° via the elastic release member.

[0174] Clause 75: The injection device according to Clause 65, wherein the outer cap can be twisted between 0° and 135° by the elastic release member.

[0175] Clause 76: The injection device according to Clause 65, wherein the outer cap can be twisted between 0° and 180° by the elastic release member.

[0176] Clause 77: The injection device according to Clause 65, wherein the outer cap can be twisted between 0° and 225° by the elastic release member.

[0177] Clause 78: The injection device according to Clause 65, wherein the outer cap can be twisted between 0° and 270° by the elastic release member.

[0178] Clause 79: The injection device according to Clause 65, wherein the outer cap can be twisted between 0° and 315° by the elastic release member.

[0179] Clause 80: The injection device according to Clause 65, wherein the outer cap can be twisted between 0° and 360° by the elastic release member.

[0180] Clause 81: The injection device according to any one of Clauses 65 to 80, wherein twisting the outer cap includes twisting the outer cap by more than 360°.

[0181] Clause 82: The injection device according to any one of Clauses 65 to 81, the injection device further comprising an active pharmaceutical agent, wherein the active pharmaceutical agent is a spray-dried powder stored in the powder chamber.

[0182] Clause 83: The injection device according to Clause 82, wherein the active pharmaceutical agent is sodium succinate hydrocortisone.

[0183] Clause 84: The injection device according to any one of Clauses 65 to 83, wherein the outer cap can engage with the housing to cover and protect the needle cap.

[0184] Clause 85: The injection device according to any one of Clauses 65 to 84, wherein the cross-section of the housing is in a teardrop shape.

[0185] Clause 86: The injection device according to any one of Clauses 65 to 85, wherein the housing includes a powder inspection window, and the powder inspection window is arranged near the position of the powder chamber:

[0186] Clause 87: An injection device according to any one of Clauses 65 to 86, wherein the housing includes a powder inspection window, the powder inspection window being provided near the position of the powder chamber, the powder inspection window providing an observation of the powder chamber such that a first mixing of the active agent and the diluent takes place.

[0187] Clause 88: An injection device according to any one of Clauses 65 to 87, wherein the housing includes a reconstitution window, the reconstitution window being provided within the wall of the housing and near the powder chamber, the reconstitution window providing an observation of the final mixing position within the injection device and near the active agent and the diluent.

[0188] Clause 89: An injection device according to Clause 88, wherein the housing further includes a powder inspection window, the powder inspection window being provided near the position of the powder chamber, the powder inspection window providing an observation of the powder chamber such that a first mixing of the active agent and the diluent takes place.

[0189] Clause 90: An injection device according to any one of Clauses 65 to 89, the injection device further including an elastic container, the elastic container being near the diluent pusher and engaging with the mixing elastic member, the elastic container being releasably engageable with the elastic release member, wherein disengaging the elastic container from the elastic release member releases the biasing force on the elastic container to actuate the diluent pusher.

[0190] Clause 91: An injection device according to Clause 90, wherein: the elastic container includes a circumferential groove; the elastic release member includes an elastic arm, wherein a cam extends from the elastic arm, the cam extending into the circumferential groove; and the elastic arm is configured to deflect radially to disengage the cam from the circumferential groove.

[0191] Clause 92: An injection device according to Clause 91, the injection device further including a fixed clamp, the fixed clamp engaging with the housing at the distal end of the mixing elastic member, the fixed clamp including a lever extension that extends proximally and into the housing.

[0192] Clause 93: An injection device according to Clause 92, wherein the lever extension is positioned near the elastic arm and the lever extension is capable of engaging with the elastic arm, wherein the elastic arm is configured to engage with the lever extension in response to rotation of the elastic release member, thereby causing the elastic arm to deflect radially.

[0193] It should be understood that the terms used herein are for the purpose of describing particular embodiments only and are not intended to limit the scope of the present disclosure, which is limited only by the appended claims.

[0194] The scope herein may be expressed as from “about” a particular value and / or to “about” another particular value. When expressing such a scope, unless the context clearly indicates otherwise, the disclosed scope should also be specifically considered and regarded as being from a particular value and / or to another particular value. Similarly, when a numerical value is expressed as an approximation by using the prefix “about” or “approximately”, it should be understood that, unless the context clearly indicates otherwise, that particular value constitutes another specifically considered and disclosed embodiment. It will also be understood that, unless the context clearly indicates otherwise, each endpoint value of a range is significant with respect to the other endpoint value and is independent of the other endpoint value. As used herein, the terms “about” or “approximately” when referring to a measurable value (such as an amount, a time duration, etc.) are intended to cover variations of ±20%, ±10%, ±5%, ±1%, ±0.5%, or ±0.1% relative to the specified value, as such variations are appropriate for carrying out the disclosed methods.

[0195] “Optional” or “optionally” means that the subsequently described event, circumstance, or material may or may not occur or exist, and the description includes the case where the event, circumstance, or material occurs or exists and the case where it does not occur or exist.

[0196] The phrase “and / or” as used in this specification and the claims should be understood to mean “either or both” of the connected elements, i.e., these elements exist in some cases in a conjunctive manner and in other cases in a disjunctive manner. Unless explicitly stated otherwise, other elements may optionally exist in addition to the elements specifically identified in the “and / or” clause, regardless of whether these other elements are related to the specifically identified elements. Thus, as a non-limiting example, when referring to “A and / or B” in combination with open-ended language such as “comprising”, in some embodiments it may refer to A without B (optionally including elements other than B); in another embodiment it may refer to B without A (optionally including elements other than A); in yet another embodiment it may refer to A and B (optionally including other elements); and so on.

[0197] As used herein, the term "pharmaceutically acceptable carrier" or "pharmaceutically acceptable diluent" means an excipient, carrier or diluent that can be administered to a subject together with the agent or pharmaceutical composition disclosed herein, and the excipient, carrier or diluent is inert or does not eliminate the pharmacological activity of the active agent in the pharmaceutical composition. In some embodiments, the pharmaceutically acceptable carrier does not destroy or eliminate the pharmacological activity of the active agent / vaccine and is non-toxic when administered in a dose sufficient to deliver a therapeutically effective amount of the active agent. The term "pharmaceutically acceptable salt" of a nucleic acid as used herein can be an acid salt or a base salt that is generally considered suitable in the art for contact with human or animal tissue without producing undue toxicity, irritation, allergic response or other problems or complications. Such salts include inorganic acid salts and organic acid salts having basic residues (such as amines), and base salts or organic salts having acidic residues (such as carboxylic acids). Specific pharmaceutical salts include, but are not limited to, salts of acids such as hydrochloric acid, phosphoric acid, hydrobromic acid, malic acid, glycolic acid, fumaric acid, sulfuric acid, sulfamic acid, p-aminobenzenesulfonic acid, formic acid, p-toluenesulfonic acid, methanesulfonic acid, benzenesulfonic acid, ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, nitric acid, benzoic acid, 2-acetoxybenzoic acid, citric acid, tartaric acid, lactic acid, stearic acid, salicylic acid, glutamic acid, ascorbic acid, pamoic acid, succinic acid, fumaric acid, maleic acid, propionic acid, hydroxymaleic acid, hydroiodic acid, phenylacetic acid, alkanoic acids such as acetic acid, HOOC-(CH2)n-COOH, where n is from 0 to 4, etc. Similarly, pharmaceutically acceptable cations include, but are not limited to, sodium, potassium, calcium, aluminum, lithium and ammonium. Those of ordinary skill in the art will recognize from the present disclosure and the knowledge in the art that there are other pharmaceutically acceptable salts for the mixed virus-specific antigens or polynucleotides provided herein, including those listed in Remington's Pharmaceutical Sciences, 17th Edition, Mack Publishing Company, Easton, Pennsylvania, page 1418 (1985). Generally, pharmaceutically acceptable acid salts or base salts can be synthesized from the parent compounds containing basic or acidic moieties by any conventional chemical method. Briefly, such salts can be prepared by reacting the free acid or base form of these compounds with a stoichiometric amount of the appropriate base or acid in a suitable solvent.

[0198] As used herein, the terms "subject", "individual", "host", and "patient" are used interchangeably herein and refer to a vertebrate individual in need of diagnosis, treatment, physical therapy, or pharmaceutical injection, including but not limited to mammals or humans, particularly humans. Mammals include but are not limited to rodents, primates, humans, farm animals, cattle, pigs, goats, sheep, horses, dogs, game animals, and pets. The methods described herein are applicable to both human therapy and veterinary applications. In certain instances in the description of the present disclosure, the term "patient" refers to a human patient suffering from a specific disease or disorder. In some embodiments, the subject is a mammal, and in other embodiments, the subject is a human.

[0199] For any therapeutic agent described herein, its therapeutically effective amount can be determined initially based on preliminary in vitro studies and / or animal models. Therapeutically effective doses can also be determined from human data. The doses administered can be adjusted based on the relative bioavailability and potency of the drug administered. Adjusting the dose to achieve maximum efficacy based on the methods described above and other known methods is within the capabilities of a person of ordinary skill in the art. General principles for determining therapeutic effects can be found in Chapter 1 of Goodman and Gilman's The Pharmacological Basis of Therapeutics, 10th Edition, McGraw-Hill, New York, 2001, which is incorporated herein by reference and summarized as follows. Pharmacokinetic principles provide the basis for adjusting dosing regimens to obtain the desired therapeutic effect while minimizing unacceptable adverse reactions. Additional guidance for adjusting the dose can be obtained in situations where the plasma concentration of the drug can be measured and correlated with a therapeutic window. Pharmaceutical products are considered pharmaceutically equivalent if they contain the same active ingredient and are identical in strength or concentration, dosage form, and route of administration. Two pharmaceutically equivalent pharmaceutical products are considered bioequivalent if there are no significant differences in the bioavailability and bioavailability of their active ingredients under appropriate test conditions.

[0200] As used herein, the terms "comprise" (and any form of comprise, such as "comprise", "comprises", and "comprised"), "have" (and any form of have, such as "have" and "has"), "include" (and any form of include, such as "includes" and "include"), or "contain" (and any form of contain, such as "contains" and "contain") are inclusive or open-ended and do not exclude additional, unrecited elements or method steps.

[0201] As used herein, the term "about" means that the value is approximate and that minor variations will not significantly affect the practice of the disclosed embodiments. When the terms "about" or "approximately" are used in reference to measurable values such as amounts, time durations, etc., in this document, it is meant to encompass variations of ±10%, ±5%, ±1%, or ±0.1% relative to the specified value, as such variations are appropriate for practicing the disclosed methods. In cases where numerical limitations are used, unless the context otherwise indicates, "about" means that the value can vary by ±10%, ±5%, ±4%, ±3%, ±2%, or ±1% and still be within the scope of the disclosed embodiments.

[0202] When referring in this specification and claims to the weight parts of a particular element or component in a composition, it represents the weight relationship between that element or component and any other element or component in the composition or article expressed in weight parts. Thus, in a compound containing 2 weight parts of component X and 5 weight parts of component Y, X and Y are present in a weight ratio of 2:5, and they are present in such a ratio regardless of whether other components are present in the compound.

[0203] Unless otherwise expressly stated, the weight percentages (wt.%) of components are calculated based on the total weight of the formulation or composition in which the component is present. As used herein, the term "optional" or "optionally" means that the subsequent described event or circumstance may or may not occur, and the description includes both the case where the event or circumstance occurs and the case where it does not occur.

[0204] As used herein, the term "carrier" means a diluent, adjuvant, or excipient by which a compound is administered. A pharmaceutical carrier can be a liquid, such as water and oils, including oils of petroleum, animal, vegetable, or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil, etc. A pharmaceutical carrier can also be saline, gum arabic, gelatin, starch paste, talc, keratin, colloidal silica, urea, etc. In addition, adjuvants, stabilizers, thickeners, lubricants, and coloring agents can also be used. A pharmaceutical composition comprises a compound in a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers refer to sterile aqueous or non-aqueous solutions, dispersions, suspensions, or emulsions, as well as sterile powders that can be reconstituted into sterile injectable solutions or dispersions before use. Examples of suitable aqueous and non-aqueous carriers, diluents, solvents, or excipients include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, etc.), carboxymethyl cellulose and its suitable mixtures, vegetable oils (such as olive oil), and injectable organic esters (such as ethyl oleate). Compounds can be formulated according to conventional techniques, such as those disclosed in Remington: The Science and Practice of Pharmacy, 19th Edition, edited by Gennaro, Mack Publishing Co., Easton, Pennsylvania, 1995, using pharmaceutically acceptable carriers or diluents and any other known adjuvants and excipients. The term "pharmaceutically acceptable carrier" is well recognized in the art and includes pharmaceutically acceptable materials, compositions, or excipients suitable for administering the compounds of the present invention to a mammal. Carriers include liquid or solid fillers, diluents, excipients, solvents, or encapsulating materials that are used to carry or transport a target agent from one organ or body part of the body to another organ or body part of the body. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients in the formulation and not harmful to the patient. Some examples of materials that can be used as pharmaceutically acceptable carriers include: sugars, such as lactose, glucose, and sucrose; starches, such as corn starch and potato starch; cellulose and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose, and cellulose acetate; tragacanth powder; malt; gelatin; talc; excipients, such as cocoa butter and suppository waxes; oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; diols, such as propylene glycol; polyols, such as glycerol, sorbitol, mannitol, and polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffering agents, such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethanol; phosphate buffer solutions; and other non-toxic and compatible substances employed in pharmaceutical formulations.Suitable pharmaceutical carriers are described in E.W. Martin's *Remington's Pharmaceutical Sciences*, the full text of which is incorporated herein by reference.

[0205] Wetting agents, emulsifying agents and lubricants such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, release agents, coating agents, sweetening agents, flavoring agents and fragrances, preservatives and antioxidants may also be present in these compositions.

[0206] Examples of pharmaceutically acceptable antioxidants include: water-soluble antioxidants such as ascorbic acid, cysteine hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite, etc.; oil-soluble antioxidants such as ascorbyl palmitate, butylated hydroxyanisole (BHA), dibutylhydroxytoluene (BHT), lecithin, propyl gallate, α-tocopherol, etc.; and metal chelating agents such as citric acid, ethylenediaminetetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid, etc.

[0207] It should be understood that all individual values and sub-ranges of values included within the explicitly disclosed ranges have also been specifically considered and are to be regarded as disclosed, unless the context clearly indicates otherwise. The foregoing applies regardless of whether some or all of these embodiments are explicitly disclosed in a particular instance.

Claims

1. An injection device for delivering a solution of an active agent and a diluent to a subject, the injection device comprising: A housing; An elastic release member; An outer cap that is separably engageable with and rotatable with the elastic release member; A diluent pusher that includes a stopper; A mixing elastic member adjacent to the diluent pusher to provide a biasing force to the diluent pusher within the housing; A powder cylinder that includes a first pierceable seal and a second pierceable seal; A crown gear positioned near the second pierceable seal and configured to pierce the second pierceable seal in response to proximal translation of the powder cylinder within the housing; and A fluid chamber disposed between the stopper and the first pierceable seal.

2. The injection device according to claim 1, further comprising a mixing chamber seal that is movable within the housing in response to positive pressure caused by proximal translation of the diluent pusher via the mixing elastic member.

3. The injection device according to claim 2, further comprising: A latch connected to the mixing chamber seal; And A needle hub that is engageable with the latch.

4. The injection device according to claim 2, further comprising: A needle-like member; A needle cap; And A needle cap elastic member.

5. The injection device according to claim 2, wherein, The outer cap is twistable between 0° and 20° via the elastic release member.

6. The injection device according to claim 2, wherein, The outer cap is twistable between 0° and 45° via the elastic release member.

7. The injection device according to claim 2, wherein, The outer cap is twistable between 0° and 90° via the elastic release member.

8. The injection device according to claim 2, wherein, The outer cap is twistable between 0° and 135° via the elastic release member.

9. The injection device according to claim 2, wherein, The outer cap is twistable between 0° and 180° via the elastic release member.

10. The injection device according to claim 2, wherein, The outer cap is twistable between 0° and 225° via the elastic release member.

11. The injection device according to claim 2, wherein, The outer cap is twistable between 0° and 270° via the elastic release member.

12. The injection device according to claim 2, wherein, The outer cap is twistable between 0° and 315° via the elastic release member.

13. The injection device according to claim 2, wherein, The outer cap is twistable between 0° and 360° via the elastic release member.

14. The injection device according to claim 2, wherein, Twisting the outer cap includes twisting the outer cap by more than 360°.

15. The injection device according to claim 2, further comprising an active agent disposed within the powder cylinder.

16. The injection device according to claim 15, wherein, The active agent is a spray-dried powder stored in the powder cylinder.

17. The injection device according to claim 16, wherein, The active agent is sodium hydrocortisone succinate.

18. The injection device according to claim 16, wherein, The powder cylinder includes more than 75 mg of spray-dried powder.

19. The injection device according to claim 1, wherein, The outer cap is engageable with the housing to cover and protect the needle cap.

20. The injection device according to claim 1, wherein, The cross-section of the housing is in a teardrop shape.

21. The injection device according to claim 1, wherein, The housing includes a powder inspection window disposed near the position of the powder cylinder.

22. The injection device according to claim 1, wherein, The housing includes a powder inspection window, which is arranged near the position of the powder cylinder, and the powder inspection window provides an observation of the powder cylinder before or during the first mixing of the active agent and the diluent.

23. The injection device according to claim 1, wherein, The housing includes a reconstitution window, which is arranged within the wall of the housing and near the crown member, and the reconstitution window provides an observation of the position near the final mixing of the active agent and the diluent within the injection device.

24. The injection device according to claim 23, wherein, The housing further includes a powder inspection window, which is arranged near the position of the powder cylinder, and the powder inspection window provides an observation of the powder cylinder before or during the first mixing of the active agent and the diluent.

25. The injection device according to claim 1, wherein the injection device further comprises an elastic container, the elastic container is close to the diluent pusher and engages with the mixing elastic member, and the elastic container and the elastic release member can be releasably engaged, wherein, Detaching the elastic container from the elastic release member releases the biasing force on the elastic container to actuate the diluent pusher.

26. The injection device according to claim 25, wherein: The elastic container includes a circumferential groove; The elastic release member includes an elastic arm, and a cam extends from the elastic arm, and the cam extends into the circumferential groove; and The elastic arm is configured to deflect radially to disengage the cam from the circumferential groove.

27. The injection device according to claim 26, the injection device further includes a fixing clamp, the fixing clamp engages with the housing at the distal end of the mixing elastic member, the fixing clamp includes a lever extension, and the lever extension extends proximally and extends into the housing.

28. The injection device according to claim 27, wherein, The lever extension is positioned near the elastic arm and the lever extension can engage with the elastic arm, wherein the elastic arm is configured to engage with the lever extension in response to the rotation of the elastic release member, thereby causing the elastic arm to deflect radially.

29. A method of administering an active agent to a subject by an injection device, the method comprising: Twisting the outer cap of the injection device to initiate the mixing of the active agent and the diluent, and initiating the mixing includes the following steps: Actuating the elastic release member to release the mixing elastic member, so that the mixing elastic member provides an axial force to the diluent pusher, thereby causing the diluent pusher to translate proximally through the injection device; Using the diluent pusher to pierce the first pierceable seal and provide an axial force to the powder cylinder, so that the diluent pusher and the powder cylinder translate proximally through the injection device towards the crown member; Piercing, via the crown member, a second pierceable seal positioned at the proximal ends of the diluent pusher and the powder cylinder, so that the active agent and the diluent begin to mix into at least a partially mixed solution; and Transferring, via the force from the mixing elastic member, the at least partially mixed solution between the crown members and towards the mixing chamber seal, wherein the force of the at least partially mixed solution passing through the crown member causes the mixing chamber seal to translate proximally and form a mixing chamber, in which the active agent and the diluent are completely mixed into a completely mixed solution.

30. The method according to claim 29, wherein the method further comprises pre-filling the fully mixed solution for injection, wherein, Priming includes the following steps: In response to the proximal translation of the mixing chamber seal, the mixing chamber seal is pierced using a needle-like member; and Via the force from the mixing elastic member acting on the active agent and the diluent, a latch fixed to the mixing chamber seal is translated proximally towards the needle seat, wherein the proximal translation of the mixing chamber seal and the latch loads the injection elastic member.

31. The method according to claim 30, wherein, Priming further includes the step of deflecting the latch such that the latch engages with a deflecting member to fix the needle seat, thereby holding the injection elastic member in a compressed position.

32. The method according to claim 30, the method further comprising: Removing the outer cap from the injection device; and Injecting the fully mixed solution, the injection comprising the steps of: Placing the proximal end of the needle cap at the skin of a subject and moving the housing of the injection device proximally such that the needle cap translates distally relative to the housing and independently of the needle-like member, such that the proximal end of the needle-like member exits the needle cap proximally; In response to the distal translation of the needle cap, causing the needle seat to translate distally within the injection device to generate pressure in the fully mixed solution between the needle seat and the diluent pusher; and Delivering the fully mixed solution through the needle-like member by means of the pressure.

33. The method according to claim 32, the method further comprising: Removing the needle-like member from the skin by pulling the injection device away from the subject; and The needle-like member is sheathed by the needle cap via a needle cap elastic member.

34. The method according to claim 33, the method further comprising permanently sheathing the needle-like member by the needle cap via the needle cap elastic member.

35. The method according to claim 32, wherein Delivering the fully mixed solution includes delivering approximately 1 mL of the fully mixed solution.

36. The method according to claim 32, wherein, Delivering the fully mixed solution includes delivering less than 1 mL of the fully mixed solution.

37. The method according to claim 32, wherein, Delivering the fully mixed solution includes delivering approximately 2 mL of the fully mixed solution.

38. The method according to claim 32, wherein, Delivering the fully mixed solution includes delivering less than 2 mL of the fully mixed solution.

39. The method according to claim 32, wherein, Delivering the fully mixed solution includes delivering more than 2 mL of the fully mixed solution.

40. The method according to claim 32, wherein, Delivering the fully mixed solution can be accomplished at any angle relative to the horizontal direction.

41. The method according to claim 29, wherein, The active agent is a spray-dried powder stored in the powder cylinder.

42. The method according to claim 41, wherein, The active agent is sodium hydrocortisone succinate.

43. The method according to claim 41, wherein The powder cylinder contains more than 75 mg of spray-dried powder.

44. The method according to claim 29, wherein, Twisting the outer cap includes twisting the outer cap relative to the housing between 0° and 20°.

45. The method according to claim 29, wherein, Twisting the outer cap includes twisting the outer cap relative to the housing between 0° and 45°.

46. The method according to claim 29, wherein, Twisting the outer cap includes twisting the outer cap relative to the housing between 0° and 90°.

47. The method according to claim 29, wherein Twisting the outer cap includes twisting the outer cap relative to the housing between 0° and 135°.

48. The method according to claim 29, wherein Twisting the outer cap includes twisting the outer cap relative to the housing between 0° and 180°.

49. The method according to claim 29, wherein Twisting the outer cap includes twisting the outer cap relative to the housing between 0° and 225°.

50. The method according to claim 29, wherein Twisting the outer cap includes twisting the outer cap relative to the housing between 0° and 270°.

51. The method according to claim 29, wherein Twisting the outer cap includes twisting the outer cap relative to the housing between 0° and 315°.

52. The method according to claim 29, wherein, Twisting the outer cap includes twisting the outer cap relative to the housing between 0° and 360°.

53. The method according to claim 29, wherein Twisting the outer cap includes twisting the outer cap relative to the housing by more than 360°.

54. The method according to claim 29, wherein The active agent and the diluent are automatically and completely mixed in the mixing chamber within less than or equal to 20 seconds.

55. The method according to claim 32, the method further comprising providing an audible cue when the fully mixed solution is fully delivered through the needle.

56. A method of assembling an injection device, the method comprising: Inserting a powder cylinder containing an active agent into a syringe cylinder; Adding a diluent to the syringe cylinder; And Inserting a diluent pusher into the syringe cylinder such that the diluent is positioned between the diluent pusher and the powder cylinder, thereby creating a sterile-sealed subassembly for the diluent and the active agent.

57. The method according to claim 56, the method further comprising: Covering the syringe cylinder with an elastic container including an elastic release member; Covering the elastic container with a mixing elastic member and a fixing clamp; And Inserting the syringe cylinder and the elastic container into the housing.

58. The method according to claim 56, the method further comprising: Connecting a mixing chamber seal to a latch; Inserting the mixing chamber seal and the latch into the syringe cylinder; Inserting a needle and an injection elastic member into the syringe cylinder; And At least partially covering the syringe cylinder with a needle cap.

59. The method according to claim 56, the method further comprising manufacturing the active pharmaceutical agent, wherein, Generating the active agent includes: Adding about 1.95 g of hydrocortisone 21 - hemisuccinate API to 50 mL of acetone and stirring until a completely dissolved solution is obtained; Adding about 100 mL of WFI to the completely dissolved solution; Adding about 0.1 normal concentration of NaOH while stirring until a resulting solution with a pH value of 7.4 is obtained; Heating the resulting solution to 25 °C under vacuum using a rotary evaporator to remove acetone, thereby leaving a final solution with a volume of about 50 mL; Adding about 12.2 mg of anhydrous sodium dihydrogen phosphate and about 133 mg of disodium hydrogen phosphate to the final solution and stirring until dissolved; and Adjusting the pH value of the final solution to 7.

4.

60. The method according to claim 59, wherein, The step of manufacturing the active agent further includes spray-drying the final solution using nitrogen.

61. The method according to claim 60, the method further comprising spray-drying the final solution at an inlet temperature of 82 °C to 150 °C and an outlet temperature of 50 °C to 90 °C.

62. A method of manufacturing an active agent, the method comprising: Adding about 1.95 g of hydrocortisone 21 - hemisuccinate API to 50 mL of acetone and stirring until a completely dissolved solution is obtained; Add approximately 100 mL of WFI to the fully dissolved solution; Add approximately 0.1 normal concentration of NaOH while stirring until a resulting solution with a pH value of 7.4 is obtained; Heat the resulting solution to 25 °C using a rotary evaporator under vacuum to remove acetone, leaving a final solution with a volume of approximately 50 mL; Add approximately 12.2 mg of anhydrous sodium dihydrogen phosphate and approximately 133 mg of disodium hydrogen phosphate to the final solution and stir until dissolved; And Adjust the pH value of the final solution to 7.

4.

63. The method according to claim 62, wherein, The step of manufacturing the active pharmaceutical agent further includes spray drying the final solution using nitrogen.

64. The method according to claim 62, the method further includes spray drying the final solution under conditions where the inlet temperature is 82 °C to 150 °C and the outlet temperature is 50 °C to 90 °C.

65. An injection device for delivering a solution of an active pharmaceutical agent and a diluent to a subject, the injection device comprising: A housing; An elastic release member; An outer cap that can be detachably engaged with the elastic release member and can rotate with the elastic release member; A diluent pusher that includes a stopper; A mixing elastic member adjacent to the diluent pusher such that the housing provides a biasing force to the diluent pusher; A mixing chamber seal; A fluid chamber near the stopper; A powder chamber; And A first pierceable seal positioned between the fluid chamber and the powder chamber.

66. The injection device according to claim 65, wherein, The diluent pusher is configured to translate proximally and at least partially pierce the first pierceable seal, thereby allowing the diluent contained in the fluid chamber to enter the powder chamber and mixing the diluent with the active pharmaceutical agent positioned within the powder chamber.

67. The injection device according to claim 65, wherein, The first pierceable seal is at least partially disposed within the stopper.

68. The injection device according to claim 65, the injection device further includes a second pierceable seal positioned between the powder chamber and the mixing chamber seal.

69. The injection device according to claim 68, the injection device further includes a fluid channel disposed between the second pierceable seal and the mixing chamber seal.

70. The injection device according to claim 65, the injection device further includes: A latch connected to the mixing chamber seal; And A needle hub that can engage with the latch.

71. The injection device according to claim 65, the injection device further includes: A needle; A needle cap; And A needle cap elastic member.

72. The injection device according to claim 65, wherein, The outer cap can be twisted between 0° and 20° through the elastic release member.

73. The injection device according to claim 65, wherein, The outer cap can be twisted between 0° and 45° through the elastic release member.

74. The injection device according to claim 65, wherein, The outer cap can be twisted between 0° and 90° through the elastic release member.

75. The injection device according to claim 65, wherein, The outer cap can be twisted between 0° and 135° through the elastic release member.

76. The injection device according to claim 65, wherein, The outer cap can be twisted between 0° and 180° through the elastic release member.

77. The injection device according to claim 65, wherein, The outer cap can be twisted between 0° and 225° by the elastic release member.

78. The injection device according to claim 65, wherein, The outer cap can be twisted between 0° and 270° by the elastic release member.

79. The injection device according to claim 65, wherein, The outer cap can be twisted between 0° and 315° by the elastic release member.

80. The injection device according to claim 65, wherein, The outer cap can be twisted between 0° and 360° by the elastic release member.

81. The injection device according to claim 65, wherein, Twisting the outer cap includes twisting the outer cap by more than 360°.

82. The injection device according to claim 65, further comprising an active pharmaceutical agent, wherein, The active pharmaceutical agent is a spray-dried powder stored in the powder chamber.

83. The injection device according to claim 82, wherein, The active pharmaceutical agent is sodium hydrocortisone succinate.

84. The injection device according to claim 65, wherein, The outer cap can engage with the housing to cover and protect the needle cap.

85. The injection device according to claim 65, wherein, The cross-section of the housing is in the shape of a teardrop.

86. The injection device according to claim 65, wherein, The housing includes a powder inspection window which is arranged near the position of the powder chamber.

87. The injection device according to claim 65, wherein, The housing includes a powder inspection window which is arranged near the position of the powder chamber, and the powder inspection window provides an observation of the powder chamber such that a first mixing of the active pharmaceutical agent and the diluent occurs.

88. The injection device according to claim 65, wherein, The housing includes a reconstitution window which is arranged within the wall of the housing and near the powder chamber, and the reconstitution window provides an observation of the position within the injection device and near the final mixing position of the active pharmaceutical agent and the diluent.

89. The injection device according to claim 88, wherein, The housing further includes a powder inspection window which is arranged near the position of the powder chamber, and the powder inspection window provides an observation of the powder chamber such that a first mixing of the active pharmaceutical agent and the diluent occurs.

90. The injection device according to claim 65, wherein the injection device further comprises an elastic container, the elastic container being close to the diluent pusher and engaging with the mixing elastic member, and the elastic container and the elastic release member can be releasably engaged, wherein, Detaching the elastic container from the elastic release member releases the biasing force on the elastic container to actuating the diluent pusher.

91. The injection device according to claim 90, wherein: The elastic container includes a circumferential groove; The elastic release member includes an elastic arm, wherein a cam extends from the elastic arm and the cam extends into the circumferential groove; and The elastic arm is configured to deflect radially to disengage the cam from the circumferential groove.

92. The injection device according to claim 91, the injection device further includes a fixed clamp which engages with the housing at the distal end of the mixing elastic member, and the fixed clamp includes a lever extension which extends proximally and extends into the housing.

93. The injection device according to claim 92, wherein, The lever extension is positioned near the elastic arm and the lever extension can engage with the elastic arm, wherein the elastic arm is configured to engage with the lever extension in response to rotation of the elastic release member, thereby causing the elastic arm to deflect radially.

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