Mixing and delivery systems and needle hubs for same

Abstract

A needle hub and reconstitution device, and a system comprising the same, is described herein. The needle hub features a needle connector facing away from the housing and a transfer needle extending towards the housing. The transfer needle is designed to pierce a seal of a pharmaceutical component-mixing delivery assembly when the needle hub is in the second position. The housing can include longitudinal grooves and snapper engagement locations, while the needle hub can have snappers that engage these locations. The system described herein is intended for reconstituting and delivering mixed pharmaceutical components.

Description

MIXING AND DELIVERY SYSTEMS AND NEEDLE HUBS FOR SAMECROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No. 63 / 611,501 filed December 18, 2023 (Attorney Docket No.: 260493.000016), to U.S. Provisional Application No. 63 / 555,553 filed February 20, 2024 (Attorney Docket No.: 260493.000017), and to U.S. Provisional Application No. 63 / 644,702 filed May 9, 2024 (Attorney Docket No.: 260493.000024), each of which are incorporated by reference as if set forth in full herein.FIELD OF THE INVENTION

[0002] The present disclosure relates to syringes and corresponding needle hubs suitable for mixing a pair of components and delivering same.

[0003] More particularly, the disclosure relates to a syringe suitable for mixing a two component therapeutic, such as a solid or liquid medicament and a liquid diluent. The present disclosure also relates to novel detachably attachable needle hubs to deliver the mixed medicament from the syringe.BACKGROUND

[0004] Many medicaments are unsuitable for the long-term storage as a liquid solution because they may be unstable when mixed into a solution and thus have a shorter shelflife than other forms. Such medicaments may be reconstituted with a diluent or carrier, usually a liquid, prior to administration. Thus, liquid or solid medicaments may be stored in a sealed vial prior to reconstitution. Increasingly, prefilled syringes capable of separate storage of at least two different components are being used. Such syringes usually comprise a medicinal component stored in a first chamber and a dissolving or dispersing component in a second chamber. The components are kept apart until use.

[0005] Dual chamber syringes have been developed which can suitably be used with powdered or liquid medicaments and a suitable liquid diluent. Such dual chambers may be used for the administration of “biopharmaceuticals,” such as recombinant proteins; and the like. One disadvantage of dual chamber syringes on the market is that they areexpensive to manufacture and can lack simplicity for the end-user. Producing a lyophilized powdered medicament in situ in the syringe can also be difficult and does not lend itself to rapid and large scale manufacturing techniques. These and other issues exist.SUMMARY

[0006] The present disclosure provides solutions to the aforementioned issues. The disclosure provides example syringes and corresponding needle hubs suitable for mixing a pair of components and delivering same. More particularly, the solutions described herein relate to detachably attachable needle hubs to deliver the mixed medicament from the syringe.

[0007] An aspect of the present disclosure provides a syringe assembly. The syringe assembly includes a housing. The syringe assembly includes a needle hub engageable with the housing and movable from a first position with respect to the housing to a second position with respect to the housing. The needle hub includes a needle connector positioned such that it faces away from the housing when the needle hub is engaged with the housing. The needle hub includes a transfer needle positioned such that it extends toward the housing when the needle hub is engaged with the housing, the transfer needle configured to pierce a seal of a pharmaceutical component-mixing delivery assembly when the needle hub is moved from the first position to the second position.

[0008] Another aspect of the present disclosure provides a method. The method includes connecting a needle hub to a distal end of a housing. The method includes inserting a pharmaceutical component-mixing delivery assembly into a proximal end of the housing. The method includes securing the pharmaceutical component-mixing delivery assembly within the housing. The method includes moving the needle hub from a first position with respect to the housing to a second position with respect to the housing, such that a transfer needle of the needle hub moves proximally toward the pharmaceutical component-mixing delivery assembly. The method includes piercing, in response to proximal movement of the transfer needle, a seal of the pharmaceutical componentmixing delivery assembly with the transfer needle.BRIEF DESCRIPTION OF THE DRAWINGS

[0009] FIGs. 1 (a) to (d) are cross-sectional views of a pharmaceutical componentmixing delivery assembly comprising a ball valve component.

[0010] FIGs. 2 (a) to (d) are cross-sectional views of a pharmaceutical componentmixing delivery assembly comprising a ball valve component provided with ball displacement means.

[0011] FIGs. 3 (a) to (e) are cross-sectional views of a pharmaceutical componentmixing delivery assembly comprising a T-valve component.

[0012] FIGs. 4 (a) to (e) are cross-sectional views of a pharmaceutical componentmixing delivery assembly comprising an “annular valve” component.

[0013] FIGs. 5 (a) to (d) are cross-sectional views of a sealed pharmaceutical component-mixing delivery assembly comprising a partially threaded plunger and “needle valve” component.

[0014] FIGs. 6 (a) to (d) are cross-sectional views of a pharmaceutical componentmixing delivery assembly comprising a spigot plug component.

[0015] FIGs. 7 (a) and 7 (b) are cutaway perspective views of a pharmaceutical component-mixing delivery assembly comprising a spigot plug component of FIG. 6; and FIG. 7 (c) is a perspective view of the delivery assembly of FIG. 6.

[0016] FIGs. 8 (a) to (d) are cross-sectional views of a pharmaceutical componentmixing delivery assembly comprising a hollow plug component.

[0017] FIGs. 9 (a) and 9 (b) are cutaway perspective views of a pharmaceutical component-mixing delivery assembly comprising a hollow plug component of FIG. 8; FIG. 9 (c) is a perspective view of the delivery assembly of FIG. 8.

[0018] FIGs. 10 (a) and (b) are cross-sectional views of a pharmaceutical componentmixing delivery assembly comprising a ribbed non-invasive valve component.

[0019] FIGs. 11 (a) and 11 (b) are cutaway perspective views of a pharmaceutical component-mixing delivery assembly comprising ribbed non-invasive valve component of FIG. 10.

[0020] FIG. 11 (c) is a perspective view of the delivery assembly of FIG. 10.

[0021] FIG. 12 is a cutaway perspective view of a non-invasive valve component of a pharmaceutical component-mixing delivery assembly.

[0022] FIG. 13 A shows a disassembled needle hub and a transfer needle, and FIG. 13B shows the needle hub of FIG. 13 A assembled.

[0023] FIG. 14A shows an example housing.

[0024] FIG. 14B shows a housing with a needle hub connected thereto, and FIG. 14C is a cross-sectional view of the housing with needle hub shown in FIG. 14B.

[0025] FIG. 15A is a detailed view of a needle hub assembled to a housing prior to attaching a delivery needle, and FIG. 15B is a detailed view of the assembly of FIG. 15A after attaching the delivery needle.

[0026] FIG. 16A shows the step of assembling a pharmaceutical component-mixing delivery assembly with a housing comprising a needle hub, and FIG. 16B shows the assembly, housing, and needle hub assembled.

[0027] FIG. 17A shows the step of adding an end cap to the assembly shown in FIG. 16B, and FIG. 17B shows the assembly assembled with the end cap.

[0028] FIG. 18A shows the step of adding a plunger to the assembly shown in FIG. 17B, and FIG. 18B shows the assembly assembled with the plunger.

[0029] FIG. 19 shows a fully assembled device with a needle hub after delivering a reconstituted medicaments using the device.

[0030] FIG. 20 is a perspective view of a hub housing with an angled groove for engaging with lugs on a needle hub.

[0031] FIG. 21A is a cross-sectional view of a needle hub with lugs engageable with the angled groove of FIG. 20.

[0032] FIG. 21B is a top plan view of the needle hub of FIG. 21A.

[0033] FIG. 22A shows a needle hub with lugs engaged in a starting slot of a housing with an angled groove.

[0034] FIG. 22B is a schematic of a track for a twistable needle hub, the track having wall snaps.

[0035] FIG. 22C shows the needle hub of FIGs. 23A and 23B positioned on a housing.

[0036] FIG. 23A is a proximal-to-distal-end perspective view of a needle hub with inward-facing lugs.

[0037] FIG. 23B is a distal-to-proximal-end perspective view of the needle hub of FIG. 23A.

[0038] FIG. 23C shows an example perforated seal that is usable with a twistable needle hub.

[0039] FIG. 23D shows the seal of FIG. 23C rolled as it would be assembled on a needle hub / housing assembly.

[0040] FIG. 23E shows the seal of FIGs. 23C and 23D added to a needle hub / housing assembly.

[0041] FIG. 23F shows an alternative design for a perforated seal.

[0042] FIG. 23G shows the perforated seal of FIG. 23F added to a needle hub assembly.

[0043] FIG. 24A is a schematic of a track for a twistable needle hub, the track having an ending slot that is a vertical track.

[0044] FIG. 24B is a schematic of a track for a twistable needle hub, the track having starting and ending slots that are vertical tracks.

[0045] FIG. 25 is a schematic of a track for a twistable needle hub, the track having an ending slot that is a horizontal track.

[0046] FIG. 26 is a perspective view of a housing with distal threads to engage with a needle hub.

[0047] FIG. 27A is a cross sectional view of a housing with a distal loading chamfer.

[0048] FIG. 27B is a cross sectional view of a needle hub with a gas vent and a circumferential seal.

[0049] FIG. 28 is a flowchart for an example method for using a syringe assembly.

[0050] FIGs. 29A-29F show steps to fill a pharmaceutical component-mixing delivery assembly. FIG. 29A shows the step of adding a spigot plug component to a first cartridge.

[0051] FIG. 29B shows the step of adding a first pharmaceutical component to the first cartridge.

[0052] FIG. 29C shows the step of adding a plunger stopper to the first cartridge.

[0053] FIG. 29D shows the step of adding a second pharmaceutical component into a sealed second cartridge.

[0054] FIG. 29E shows the step of adding a piston component to the first cartridge.

[0055] FIG. 29F shows the step of adding the first cartridge to the second cartridge.

[0056] FIG. 30 is a flowchart for an example method for filling a pharmaceutical component-mixing delivery assembly via a real-fill method.

[0057] FIGs. 31 A-31G show steps to fill a pharmaceutical component-mixing delivery assembly. FIG. 31 A shows the step of adding a spigot plug component to a first cartridge.

[0058] FIG. 3 IB shows the step of adding a first pharmaceutical component to the first cartridge.

[0059] FIG. 31C shows the step of adding a plunger stopper to the first cartridge.

[0060] FIG. 3 ID shows the step of adding a piston component to the first cartridge.

[0061] FIG. 3 IE shows the step of adding the first cartridge of FIG. 3 ID to an empty and distally-open second cartridge.

[0062] FIG. 3 IF shows the step of inverting the assembly shown in FIG. 3 IE and adding a second pharmaceutical component into the distal end of the second cartridge.

[0063] FIG. 31G sealing the distal end of the second cartridge with a cartridge cap.

[0064] FIG. 32 is a flowchart for an example method for filling a pharmaceutical component-mixing delivery assembly via a tip-fill method.

[0065] FIG. 33 is a flowchart showing a method of manufacturing an active pharmaceutical component , according to aspects of the present disclosure.

[0066] FIG. 34 is a table showing results of testing a spray dried hydrocortisone sodium succinate as prepared using the method of FIG. 33.

[0067] FIG. 35 is a table showing example spray-drying conditions for hydrocortisone sodium succinate, according to aspects of the present disclosure.

[0068] FIGs. 36A-36C are cross-sectional views showing use of a syringe assembly.DETAILED DESCRIPTION

[0069] The present disclosure can be understood more readily by reference to the following detailed description of exemplary embodiments and the examples included herein. Before the exemplary embodiments of the devices and methods according to the present disclosure are disclosed and described, it is to be understood that embodiments are not limited to those described within this disclosure. Numerous modifications and variations therein will be apparent to those skilled in the art and remain within the scope of the disclosure. It is also to be understood that the terminology used herein is for thepurpose of describing specific embodiments only and is not intended to be limiting. Some embodiments of the disclosed technology will be described more fully hereinafter with reference to the accompanying drawings. This disclosed technology may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth therein.

[0070] In the following description, numerous specific details are set forth. But it is to be understood that embodiments of the disclosed technology may be practiced without these specific details. In other instances, well-known methods, structures, and techniques have not been shown in detail in order not to obscure an understanding of this description. References to “one embodiment,” “an embodiment,” “example embodiment,” “some embodiments,” “certain embodiments,” “various embodiments,” etc., indicate that the embodiment(s) of the disclosed technology so described may include a particular feature, structure, or characteristic, but not every embodiment necessarily includes the particular feature, structure, or characteristic. Further, repeated use of the phrase “in one embodiment” does not necessarily refer to the same embodiment, although it may.

[0071] Unless otherwise noted, the terms used herein are to be understood according to conventional usage by those of ordinary skill in the relevant art. In addition to any definitions of terms provided below, it is to be understood that as used in the specification and in the claims, “a” or “an” can mean one or more, depending upon the context in which it is used. Throughout the specification and the claims, the following terms take at least the meanings explicitly associated herein, unless the context clearly dictates otherwise. The term “or” is intended to mean an inclusive “or.” Further, the terms “a,” “an,” and “the” are intended to mean one or more unless specified otherwise or clear from the context to be directed to a singular form.

[0072] Unless otherwise specified, the use of the ordinal adjectives “first,” “second,” “third,” etc., to describe a common object, merely indicate that different instances of like objects are being referred to, and are not intended to imply that the objects so described must be in a given sequence, either temporally, spatially, in ranking, or in any other manner.

[0073] Also, in describing the exemplary embodiments, terminology will be resorted to for the sake of clarity. It is intended that each term contemplates its broadest meaningas understood by those skilled in the art and includes all technical equivalents that operate in a similar manner to accomplish a similar purpose.

[0074] To facilitate an understanding of the principles and features of the embodiments of the present disclosure, exemplary embodiments are explained hereinafter with reference to their implementation in an illustrative embodiment. Such illustrative embodiments are not, however, intended to be limiting.

[0075] The materials described hereinafter as making up the various elements of the embodiments of the present disclosure are intended to be illustrative and not restrictive. Many suitable materials that would perform the same or a similar function as the materials described herein are intended to be embraced within the scope of the example embodiments. Such other materials not described herein can include, but are not limited to, materials that are developed after the time of the development of the disclosed technology, for example.

[0076] Embodiments of the disclosed technology include detachably attachable needle hubs that can be used to deliver mixed medicament from a dual chambered reconstitution device. But examples of the disclosed technology are not so limited. The disclosed needle hub devices and techniques may be effective in delivering medicament from other fluid delivery devices, including for example single-chamber fluid delivery devices, or even fluid delivery devices with more than two separate chambers / compartments. Also, the devices described herein can be used to deliver any number of medicaments. Some examples described herein can include reconstituting a pharmaceutical component (e.g., the later mentioned second pharmaceutical component (11) within second cartridge (3)) using another pharmaceutical component (usually a liquid, see for example the later mentioned first pharmaceutical component (7) within first cartridge (2)). It will be understood that the second pharmaceutical component (11) can be a solid component (e.g., a powder) that is created, for example and not limitation, via lyophilization or spraydrying.

[0077] According to one aspect of the present disclosure there is described a pharmaceutical component-mixing delivery assembly comprising: a first cartridge and a second cartridge; the first and second cartridges being dimensioned so that they are movable relative to one another such that the first cartridge is slidable within the secondcartridge from a pre-mixed position to a post-mixed position; the first cartridge comprising a body provided with an outlet end, the first cartridge being fitted with plunger and containing a first pharmaceutical component; the second cartridge comprising a body provided with an inlet end and an outlet end, the second cartridge containing a second pharmaceutical component; and wherein the first and second cartridges are separated by a non-invasive valve component.

[0078] In a particular embodiment the non-invasive valve component, e.g., comprising a piston, can include a terminal rib, that is, a circumferential rib located at the end of the non-invasive valve component nearest to the open end of the second cartridge. The inclusion of a terminal rib is advantageous in that, inter alia, it allows the sterility of the delivery assembly to be maintained when the device is primed before injection.

[0079] Furthermore, the non-invasive valve component, e.g., a piston, may be generally elongated. The region of the second cartridge that contains the second pharmaceutical component can include an aseptic mixing chamber, whilst the inner wall of the second cartridge outside of the mixing chamber and beyond the terminal rib of the piston, will generally be non-aseptic. In use, as the plunger of the delivery assembly is depressed and the piston moves towards the inlet end of the second cartridge, the mixing chamber essentially expands longitudinally. Thus, the length of the piston is desirably chosen so that as the piston moves, the mixing chamber never comes into contact with the nonaseptic walls of the second cartridge and the sterility of the mixing chamber is maintained at all times. Therefore, the length of the piston will be dictated by how far back along the second cartridge it has to move, which will in turn be dictated by the volume required for the mixing chamber.

[0080] The non-invasive valve component can comprise a ball valve, a flow through stopper component or a T-shaped stopper component.

[0081] The pharmaceutical component-mixing delivery assembly can include a syringe assembly. Thus, the pharmaceutical component-mixing delivery assembly hereinbefore described may include a needle, e.g., a hypodermic needle, attached to the outlet end of the second cartridge.

[0082] One of the first and second pharmaceutical components may comprise a solid therapeutically active component or agent, and the other is a liquid capable of solubilizingor forming a suspension with the solid therapeutically active component. In a particular aspect of the disclosure the first pharmaceutical component comprises a liquid and the second pharmaceutical component comprises a solid therapeutically active component. However, it will be understood by the person skilled in the art that the first and second pharmaceutical components may comprise liquid / liquid components, viscous / non- viscous components, etc.

[0083] The first and second pharmaceutical component of the present invention may include any and all active ingredients considered appropriate, normal, standard, and / or typical for treating a target disease, disorder, or condition, including drugs at any stage of the drug development process / pipeline, including but not limited to, active ingredients that are in preclinical development, drugs undergoing clinical trials / marketing approval, drugs approved for use, marketed drugs, and / or drugs in early, middle, or late stages of development, including repurposed and / or reformulated drugs. General mention is made of any and all hormone drugs, antibody therapeutics, autoinjector drugs, self-injection drugs and / or drugs involving reconstitution systems for delivery. Additional active ingredients include, but are not limited to, antibacterial (e.g. beta-lactam antibiotics, penicillins, vancomycin, ciprofloxacin), antiviral (e g. aciclovir, oseltainivir) and antifungal (e.g. naftifln, nystatin) substances and immunomodulatory and immunosuppressive compounds such as cyclosporin, Methotrexat®, TNF antagonists (e.g. Humira®, Etanercept, infliximab), IL-1 inhibitors (e.g. Anakinra, Canakinumab, Rilonacept), phosphodiesterase inhibitors (e.g. Apremilast), Jak / STAT inhibitors (e.g. Tothcitinib, Baricitinib, GLPG0634), leflunomid, cyclophosphamide, rituximab, belimuinab, tacrolimus, rapamycin, mycophenolate mofetil, interferons, corticosteroids (e.g. prednisone, prednisolone, methylprednisolone, hydrocortisone, betamethasone), cyclophosphamide, azathioprine, sulfasalazine, paracetamol and non-steroidal antiinflammatory substances (NSAIDS) (e.g., aspirin, ibuprofen, naproxen, etodolac, celecoxib, colchicine).

[0084] In some embodiments, the first and / or second pharmaceutical component of the present invention may include, but are not limited to, hydrocortisone, a hydrocortisone prodrug, or a pharmaceutically acceptable salt of hydrocortisone. In some embodiments, the hydrocortisone prodrug is a hydrocortisone ester. In some embodiments, thehydrocortisone prodrug or pharmaceutically acceptable salt thereof of hydrocortisone is selected from hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydrocortisone hydrogen succinate, hydrocortisone butyrate, and hydrocortisone acetate. In some embodiments, the hydrocortisone prodrug or pharmaceutically acceptable salt thereof is hydrocortisone sodium phosphate.

[0085] In addition to the active ingredients mentioned above, the first and second pharmaceutical component of the present invention may also include, but are not limited to, the following active ingredients: Vitamin D analogs (e.g., calcipotriol, tacalcitol or calcitriol), salicylic acid, urea, ciclosporine, methotrexate, efalizumab for treatment of dermatological disorders; methotrexate and biologies for B-cell and T-cell therapy (e.g. rituximab, abatacept) for rheumatoid disorders, for example rheumatoid arthritis, spondyloarthritis and juvenile idiopathic arthritis; substances for treatment of pulmonary disorders, for example beta-2-sympathomimetics (e g. salbutamol), anticholinergics (e g. glycopyrronium), methylxanthines (e.g. theophylline), leukotriene receptor antagonists (e.g. montelukast), PDE-4 (phosphodiesterase type 4) inhibitors (e.g. roflumilast), methotrexate, IgE antibodies, azathioprine and cyclophosphamide, cortisol-containing preparations; lipid-lowering drugs, for example, fibrates (e.g. bezafibrate, etofibrate, fenofibrate, gemfibrozil), nicotinic acid derivatives (e.g. nicotinic acid / laropiprant), ezetimib, statins (e.g. simvastatin, fluvastatin), anion exchangers (e.g. colestyramine, colestipol, colesevelam); active ingredients for treatment of cardiovascular disorders such as beta-blockers (e g. metoprolol), ACE inhibitors (e.g. benazepril), angiotensin receptor blockers (e.g. losartan, valsartan), diuretics (e.g. hydrochlorothiazide), calcium-channel blockers (e.g. nifedipine), statins (e.g. simvastatin, fluvastatin); neurotrophic substances, such as, acetylcholinesterase inhibitors (e.g. donepezil), MAO (monoaminooxidase) inhibitors (e g. selegiline), interferons and anticonvulsives (e.g. gabapentin); anti-diabetic drugs, for example metformin, glinides (e.g. rtateglinide), DPP-4 (dipeptidyl peptidase- 4) inhibitors (e.g. linagliptin, saxagliptin, sitagliptin, SGLT2 (sodium / glucose cotransporter 2) inhibitors, gliflozin (e.g. dapagliflozin, empagliflozin), incretin mimetics (hormone glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 1 (GLP-1) anal ogues / agoni sts (e.g. exenatide, hraglutide, lixisenatide), a-glucosidase inhibitors (e.g. acarbose, miglitol, voglibiose) and sulphonyl ureas (e.g. glibenclamide,tolbutamide), insulin sensitizers (e.g. pioglitazone) and insulin therapy (e.g. NPH insulin, insulin lispro), substances for treatment of hypoglycaemia, for treatment of diabetes and metabolic syndrome; beta-interferon (IFN-beta) (e.g. IFN beta-lb, IFN beta-la, Avonex® and Betaferon®), glatiramer acetate, immunoglobulins, natalizumab, fmgolimod and immunosuppressants such as mitoxantrone, azathioprine and cyclophosphamide for treatment of multiple sclerosis; and active ingredients for Alzheimer's therapy, for example, acetylcholinesterase inhibitors (e.g. donepezil, rivastigmine, galantamine, tacrine), NMDA (N-methyl-D-aspartate) receptor antagonists (e.g. memantine); L-DOPA / carbidopa (1,3,4-dihydroxyphenylalanine), COMT (catechol-O-methyltransferase) inhibitors (e.g. entacapone), dopamine agonists (e.g. ropinirole, pramipexole, bromocriptine), MAO-B (monoaminooxidase-B) inhibitors (e.g. selegiline), anticholinergics (e.g. trihexyphenidyl) and NMDA antagonists (e.g. amantadine) for treatment of Parkinson's Disease.

[0086] The use of a non-invasive valve as hereinbefore described is advantageous in that, inter alia, conventional syringe bodies and / or plungers may be utilized, significantly reducing the expense of the syringe assembly as a whole. It also avoids, for example, the need for an elastomeric septum.

[0087] In one aspect of the disclosure the non-invasive valve component may comprise a ball valve. Such a ball valve component may comprise one or more balls located within the outlet of the first cartridge, such that the ball(s) acts to seal the first cartridge. The ball valve component includes a substantially hollow apertured piston suitable for receiving the ball from the first cartridge.

[0088] More specifically, the ball valve component may comprise a substantially hollow apertured piston with a first end adjacent the outlet end of the first cartridge and a second end adjacent the inlet end of the second cartridge. The hollow apertured piston will comprise side walls which generally form a seal against the inner walls of the second cartridge.

[0089] The first end of the piston may comprise means for locating the outlet end of the first cartridge. For example, such means may comprise a substantially circumferential ridge. The second end of the piston may comprise one or more apertures which, when in use, are dimensioned to allow fluid to flow.

[0090] A single ball or a plurality, e.g., two or three balls, may be located within the outlet of the first cartridge, such that the ball(s) acts to seal the first cartridge. In use, when the plunger is depressed within the first cartridge the fluid pressure will force the ball valve to open allowing fluid to flow from the first cartridge to the second cartridge enabling mixing to occur.

[0091] In another aspect of the disclosure the non-invasive valve component may comprise a ball valve as hereinbefore described. However, the second end of the piston may comprise a separate plug component which can include one or more apertures which, when in use, are dimensioned to allow fluid to flow. In addition, the plug component may be provided with means for displacing the ball from the outlet of the first cartridge allowing fluid to flow from the first cartridge to the second cartridge enabling mixing to occur. Thus, in accordance with this aspect of the disclosure there is described a pharmaceutical component-mixing delivery assembly as hereinbefore described wherein the ball valve component includes a plug component which can include one or more apertures and which can include a means for displacing the ball from the outlet of the first cartridge. One example of such displacement means is a plug provided with a protruding spigot.

[0092] In another aspect of the disclosure the non-invasive valve component may comprise a flow through stopper component. The flow through stopper component may comprise a stopper which can include a conduit means. Said conduit means may comprise an internal conduit within the stopper or alternatively, may comprise an external conduit, that is, a conduit between the walls of the piston and the stopper.

[0093] One example of a flow through stopper component with an internal conduit is a T-valve. Such a T-valve component may comprise a substantially hollow apertured piston with a first end adjacent the outlet end of the first cartridge and a second end adjacent the inlet end of the second cartridge. The hollow apertured piston will comprise side walls which generally form a seal against the inner walls of the second cartridge as hereinbefore described.

[0094] The first end of the piston may comprise means for locating the outlet end of the first cartridge. For example, such means may comprise a substantially circumferential ridge. The piston also houses a stopper which has a flow through capability and whichseals the outlet end of the first cartridge. Said stopper may comprise an internal conduit which is substantially coaxial with the longitudinal axis of the first cartridge, but which can include one or more branches which seal against the side walls of the piston.[00951 Inuse, when the plunger is depressed within the first cartridge the fluid pressure will displace the flow through stopper such that the one or more branches of the conduit are no longer sealed against the side walls of the piston allowing fluid to flow from the first cartridge to the second cartridge enabling mixing to occur. Optionally, a second stopper may be provided adjacent the inlet of the second cartridge. The second stopper may also be provided with one or more branched conduits, which act in a substantially similar manner to the first.

[0096] In any of the embodiments described herein the side walls of the non-invasive valve component may be provided with one or more external ribs to improve the seal formed between the non-invasive valve component and the second cartridge. Thus, for example, when the non-invasive valve component comprises a piston, the piston may be ribbed, z.e., can include one or more external ribs, to improve the seal formed between the piston and the inner walls of the second cartridge. Preferably the piston can include one or more circumferential ribs. It is especially preferred for the piston to be provided with a plurality of circumferential ribs, e.g., 2, 3 or 4 ribs.

[0097] An alternative example of a flow through stopper component with an external conduit is an “annular valve”. Although an “annular valve” possesses a similar functionality to the aforementioned T-valve, the “annular valve” stopper itself does not comprise an internal conduit.

[0098] Adj acent the first cartridge the internal walls of the piston are configured to form a snug fit with the stopper. In this first position, the stopper seals the first cartridge. The piston also provides a second position wherein the stopper forms a loose fit, such a conduit external to the stopper is formed between the stopper and the piston, such that fluid may pass through the conduit, between the walls of the piston and the stopper.

[0099] Thus, according to this aspect of the disclosure there is described a pharmaceutical component-mixing delivery assembly as hereinbefore described wherein the “annular valve” comprises a piston configured to form a snug fit with a stopper which seals the first cartridge; and wherein the piston provides a second position wherein thestopper forms a loose fit, such that fluid may pass between the walls of the piston and the stopper.

[0100] The use of a T-valve is advantageous, inter alia, in that:• It provides guidance for the piston in the hollow stopper (the plug cannot tilt)• Aids assembly — physical stop• Prevents the piston being accidently drawn back into the syringe• Ribs provide enhanced sealing in the neck of the of the cartridge• The larger diameter part is held by the hollow stopper which provides additional retention of the piston

[0101] According to a further aspect of the present disclosure there is described a method of operating a pharmaceutical component-mixing delivery assembly holding first and second pharmaceutical components; said delivery assembly comprising: a first cartridge and a second cartridge; the first and second cartridges being dimensioned so that they are movable relative to one another such that the first cartridge is slidable within the second cartridge from a pre-mixed position to a post-mixed position; the first cartridge comprising a body provided with an outlet end, the first cartridge being fitted with plunger and containing a first pharmaceutical component; the second cartridge comprising a body provided with an inlet end and an outlet end, the second cartridge containing a second pharmaceutical component; and wherein the first and second cartridges are separated by a non-invasive valve component; said method comprising pressing the plunger axially into the first cartridge to an intermediate position thus pressurizing the first cartridge and opening the non-invasive valve component, causing the first pharmaceutical component to flow through the valve and into the second cartridge to mix with the second pharmaceutical component.

[0102] According to a yet further aspect of the present disclosure there is described a method of administering a therapeutically active component to a patient which comprises operating a pharmaceutical component-mixing delivery assembly holding first and second pharmaceutical components; said delivery assembly comprising: a first cartridge and a second cartridge; the first and second cartridges being dimensioned so that they are movable relative to one another such that the first cartridge is slidable within the secondcartridge from a pre-mixed position to a post-mixed position; the first cartridge comprising a body provided with an outlet end, the first cartridge being fitted with plunger and containing a first pharmaceutical component; the second cartridge comprising a body provided with an inlet end and an outlet end, the second cartridge containing a second pharmaceutical component; and wherein the first and second cartridges are separated by a non-invasive valve component; said method comprising the steps of (i) pressing the plunger axially into the first cartridge to an intermediate position thus pressurizing the first cartridge and opening the a non-invasive valve component, causing the first pharmaceutical component to flow through the valve and into the second cartridge to mix with the second pharmaceutical component; (ii) after the first and second pharmaceutical components have mixed, administering the mixed pharmaceutical components to a patient.

[0103] According to a particular aspect of the method of the disclosure the non-invasive valve component can include a terminal rib to improve the seal formed between the non- invasive valve component and the second cartridge.

[0104] The pharmaceutical component-mixing delivery assembly can include a syringe assembly. Thus, the method of administering a therapeutically active component to a patient can include an additional step of attaching a needle, e.g., a hypodermic needle, to the outlet end of the second cartridge, followed by administering the mixed pharmaceutical components to a patient.

[0105] In the aforementioned methods preferably one of the first and second pharmaceutical components comprises a solid therapeutically active component and the other is a liquid capable of solubilizing or forming a suspension with the solid therapeutically active component. In a particular aspect of the disclosure the first pharmaceutical component comprises a liquid and the second pharmaceutical component comprises a solid therapeutically active component. Alternatively, the first and second pharmaceutical components may comprise liquid / liquid components, viscous / non- viscous components, etc.

[0106] In another embodiment of the present disclosure resistance or friction may be minimized for the user by providing a plunger with an external screw thread. In this particular embodiment the plunger is desirably threaded along a predetermined portionof its length. It is within the scope of the present disclosure for the plunger to be threaded along the whole of its length; however, it is preferred that the plunger is only partially threaded, i.e., threaded along only a portion of its length. Thus, the user may screw the plunger to bring the contents of the first and second cartridges into contact, since this is generally where the user experiences most resistance. However, the remainder of the shaft of the plunger may desirably be unthreaded so that a conventional push action may be used for administration of the medicament solution to a patient.

[0107] The use of a threaded, or partially threaded, plunger as hereinbefore described may also be advantageous in that it may be used to provide a sealed system, improving sterility of the delivery device. Thus, a frangible seal may be provided around the shaft of the plunger, for example, within the body of the first cartridge, such that twisting of the plunger by the user can cause the frangible seal to break.

[0108] The use of a threaded plunger may suitably be used with any of the aforementioned syringe embodiments hereinbefore described. However, it will be understood by the person skilled in the art that such a threaded plunger arrangement is novel per se and may therefore be suitably applied to a conventionally known valve component, such as a needle piercing an elastomeric septum. Desirably, the pharmaceutical component-mixing delivery assembly according to this aspect of the disclosure can include a sealed unit, e.g., an outer casing which house the first and second cartridges.

[0109] A particular advantage of the use of a threaded plunger is that a seal may be placed around the end of the first cartridge by, i.e., between the first cartridge and the outer casing.

[0110] Thus, according to this further aspect of the present disclosure there is described a pharmaceutical component-mixing delivery assembly comprising: an outer casing is provided which houses a first and a second cartridge; the first and second cartridges being dimensioned so that they are movable relative to one another such that the first cartridge is slidable within the second cartridge from a pre-mixed position to a post-mixed position; the first cartridge comprising a body provided with an outlet end, the first cartridge being fitted with an at least partially threaded plunger the end of which protrudes from the outer casing, said first cartridge containing a first pharmaceutical component; the secondcartridge comprising a body provided with an inlet end and an outlet end, the second cartridge containing a second pharmaceutical component; wherein the first and second cartridges are separated by a valve component; and a frangible seal is provided between the outer casing and the first cartridge.

[0111] In use, when the at least partially threaded plunger is twisted the frangible seal is broken; then as the at least partially threaded plunger and the cartridge are pushed towards the second cartridge the first cartridge disengages from the seal. The use of a frangible seal enables the device to remain sterile during storage, whilst the disengagement of the frangible seal from the first cartridge reduces friction and lowers force required to complete the administration of the therapeutically active component.

[0112] According to this aspect of the disclosure the valve component may comprise a non-invasive valve as hereinbefore described or a conventionally known valve, such as a needle valve or a bypass valve.

[0113] In a further aspect of the disclosure there is described a method of administering a therapeutically active component to a patient which comprises operating a pharmaceutical component-mixing delivery assembly holding first and second pharmaceutical components; said delivery assembly comprising: an outer casing is provided which houses a first and a second cartridge; the first and second cartridges being dimensioned so that they are movable relative to one another such that the first cartridge is slidable within the second cartridge from a pre-mixed position to a post-mixed position; the first cartridge comprising a body provided with an outlet end, the first cartridge being fitted with an at least partially threaded plunger the end of which protrudes from the outer casing, said first cartridge containing a first pharmaceutical component; the second cartridge comprising a body provided with an inlet end and an outlet end, the second cartridge containing a second pharmaceutical component; wherein the first and second cartridges are separated by a valve component; and a frangible seal is provided between the outer casing and the first cartridge.

[0114] The method of operation according to this aspect of the disclosure can include first turning the at least partially threaded plunger causing the frangible seal to break and disengage from the first cartridge and subsequently pressing the plunger to administer the mixed pharmaceutical components to a patient.

[0115] The term “non-invasive valve” will be understood by the person skilled in the art. However, for the avoidance of doubt, the term should be construed so as not to include a component wherein, for example, a needle is utilized to pierce a septum and the like. Furthermore, the term “non-invasive valve component” should be construed as meaning that the valve is made up entirely of the component, i.e., it does not utilize the wall of the syringe or cartridge.

[0116] According to a yet further aspect of the disclosure there is described a kit suitable for mixing and delivery of pharmaceutical components, said kit comprising: a first cartridge and a second cartridge; the first and second cartridges being dimensioned so that when placed together they are movable relative to one another such that the first cartridge is slidable within the second cartridge from a pre-mixed position to a post-mixed position; the first cartridge comprising a body provided with an outlet end, the first cartridge being fitted with plunger and containing a first pharmaceutical component; the second cartridge comprising a body provided with an inlet end and an outlet end, the second cartridge containing a second pharmaceutical component; and wherein when the first and second cartridges are placed together they are separated by a non-invasive valve component.

[0117] The present disclosure also describes a kit suitable for mixing and delivery of pharmaceutical components, said kit comprising: an outer casing which houses a first and a second cartridge; the first and second cartridges being dimensioned so that they are movable relative to one another such that the first cartridge is slidable within the second cartridge from a pre-mixed position to a post-mixed position; the first cartridge comprising a body provided with an outlet end, the first cartridge being fitted with an at least partially threaded plunger the end of which protrudes from the outer casing, said first cartridge containing a first pharmaceutical component; the second cartridge comprising a body provided with an inlet end and an outlet end, the second cartridge containing a second pharmaceutical component; wherein the first and second cartridges are separated by a valve component; and a frangible seal is provided between the outer casing and the first cartridge.

[0118] The disclosure further describes the use of a pharmaceutical component-mixing delivery assembly comprising: a first cartridge and a second cartridge; the first and secondcartridges being dimensioned so that they are movable relative to one another such that the first cartridge is slidable within the second cartridge from a pre-mixed position to a post-mixed position; the first cartridge comprising a body provided with an outlet end, the first cartridge being fitted with plunger and containing a first pharmaceutical component; the second cartridge comprising a body provided with an inlet end and an outlet end, the second cartridge containing a second pharmaceutical component; and wherein the first and second cartridges are separated by a non-invasive valve component; for the mixing and delivery of a first and second pharmaceutical component. According to this aspect of the disclosure the non-invasive valve component can include a terminal rib to improve the seal formed between the non-invasive valve component and the second cartridge.

[0119] Reference will now be made to the figures, in which similar structures will be provided with similar reference designations. Referring to FIGs. 1 (a) to (d) a pharmaceutical component-mixing delivery assembly (1) comprises a first cartridge (2) and a second cartridge (3), the first cartridge (2) being dimensioned so that it is slidable within the second cartridge (3) from a pre-mixed position to a post-mixed position. The first cartridge (2) comprises a body (4) provided with an outlet end (5) and a plunger (6). The first cartridge (2) contains a first pharmaceutical component (7). The second cartridge (3) comprises a body (8) provided with an inlet end (17) and an outlet end (10). The second cartridge (3) contains a second pharmaceutical component (11). A non-invasive valve component (12) separates the first and second cartridges (2) and (3).

[0120] The non-invasive valve component (12) comprises a ball valve (13) which consists of a hollow piston (14) with a first end (15) adjacent the outlet end (5) of the first cartridge (2) and a second end (16) adjacent the inlet end (17) of the second cartridge (3). The hollow piston (14) comprises a side wall (18) which generally forms a seal against the inner surface (19) of the body (8) of the second cartridge (3).

[0121] The first end (15) of the hollow piston (14) can include a circumferential recess(20) suitable for locating the outlet end (5) of the first cartridge (2). In the embodiment shown the outlet end (5) of the first cartridge (2) can include a circumferential shoulder(21) adapted to fit into the circumferential recess (20) of the first end (15) of the hollow piston (14). The second end (16) of the hollow piston (14) can include a pair of apertures(22) and (23). The outlet end (5) of the first cartridge (2) can include an orifice (24) within which sits a ball (25) which acts to seal the first cartridge (2).

[0122] In use, when the plunger (6) is depressed within the first cartridge (2) the increase in pressure will force the ball (25) out of the orifice (24), which causes the valve component (12) to open allowing the first pharmaceutical component (7), usually a fluid to flow from the first cartridge (2) through orifice (24), around ball (25), through apertures (22) and (23) and into the second cartridge (3) where it mixes with the second pharmaceutical component (11).

[0123] Referring to FIGs. 2 (a) to (d) a pharmaceutical component-mixing delivery assembly (1) comprises a first cartridge (2) and a second cartridge (3) as hereinbefore described with reference to FIGs. 1 (a) to (d). The non-invasive valve component (12) comprises a ball valve (13) which consists of a hollow piston (14) with a first end (15) adjacent the outlet end (5) of the first cartridge (2) and a second end (16) adjacent the inlet end (17) of the second cartridge (3) as hereinbefore described.

[0124] However, the second end (16) of the hollow piston (14) comprises a separate plug component (16a) which can include a pair of apertures (22) and (23). In addition, the plug component (16a) can include a substantially central spigot (16b) which protrudes from plug component (16a) towards the outlet end (5) of the first cartridge (2).

[0125] In use, when the plunger (6) is depressed within the first cartridge (2) the first cartridge (2) slides towards the plug component (16a). When the spigot (16b) comes into contact with the ball (25), the ball (25) is displaced from orifice (24), which causes the valve component (12) to open allowing the first pharmaceutical component (7), usually a fluid to flow from the first cartridge (2) through orifice (24), around ball (25), through apertures (22) and (23) and into the second cartridge (3) where it mixes with the second pharmaceutical component (11).

[0126] Referring to FIGs. 3 (a) to (e), a pharmaceutical component-mixing delivery assembly (1) comprises a first cartridge (2) and a second cartridge (3), the first cartridge (2) being dimensioned so that it is slidable within the second cartridge (3) from a premixed position to a post-mixed position. The first cartridge (2) comprises a body (4) provided with an outlet end (5) and a plunger (6). The first cartridge (2) contains a first pharmaceutical component (7). The second cartridge (3) comprises a body (8) providedwith an inlet end (17) and an outlet end (10). The second cartridge (3) contains a second pharmaceutical component (11). A non-invasive valve component (12) separates the first and second cartridges (2) and (3).

[0127] The non-invasive valve component (12) comprises a T-valve component (26). The T-valve component (26) consists of a pair of hollow pistons (27) and (28). A first hollow piston (27) is adjacent the outlet end (5) of the first cartridge (2) and a second hollow piston (28) is adjacent the inlet end (17) of the second cartridge (3). Each of the hollow pistons (27) and (28) comprises a side wall (29) and (30) respectively which generally forms a seal against the inner surface (19) of the body (8) of the second cartridge (3).

[0128] The first hollow piston (27) can include a circumferential recess (31) suitable for locating the outlet end (5) of the first cartridge (2). In the embodiment shown the outlet end (5) of the first cartridge (2) can include a circumferential shoulder (21) adapted to fit into the circumferential recess (31) of the first hollow piston (27). The first hollow piston (27) is fitted with a stopper component (32) with an internal conduit (33) which is substantially coaxial with the longitudinal axis of the first cartridge (2). The internal conduit (33) is provided with a branched conduit (34) which seals against the side wall (29) of the first hollow piston (27).

[0129] The second hollow piston (28) is fitted with a second stopper component (35) with an internal conduit (36) which is substantially coaxial with the longitudinal axis of the first cartridge (2). The internal conduit (36) can include a branch (37) which seals against the side wall (30) of the second hollow piston (28).

[0130] In use, when the plunger (6) is depressed within the first cartridge (2) the increase in pressure will force the stopper component (32) to protrude out of the first hollow piston (27). This movement causes the branched conduit (34) to be exposed and lose its seals against the side wall (29) of the first hollow piston (27) allowing the first pharmaceutical component (7), usually a fluid, to flow from the first cartridge (2) through internal conduit (33) and branched conduit (34) into the second hollow piston (28). Continued depression of the plunger (6) causes the second stopper component (35) to protrude out of the second hollow piston (28). This movement causes the branched conduit (37) to be exposed and lose its seal against the side wall (30) of the second hollowpiston (28) allowing the first pharmaceutical component (7) to flow from the first cartridge (2) and first hollow piston (27) through internal conduit (36) and branched conduit (37) into the second cartridge (3) where it mixes with the second pharmaceutical component (11).

[0131] Referring to FIGs. 4 (a) to (e), a pharmaceutical component-mixing delivery assembly (1) comprises first and second cartridges (2) and (3) as hereinbefore described.

[0132] An annular valve component (38) comprises a round stopper component (39) with a conduit external to the stopper. This is hereinafter referred to as an “annular valve”.

[0133] The annular valve component (38) consists of a pair of hollow pistons (40) and (41). A first hollow piston (40) is adjacent the outlet end (5) of the first cartridge (2) and a second hollow piston (41) is adjacent the inlet end (17) of the second cartridge (3). Each of the hollow pistons (40) and (41) comprises a side wall (42) and (43) respectively which generally forms a seal against the inner surface (19) of the body (8) of the second cartridge (3).

[0134] The first hollow piston (40) can include a circumferential recess (44) suitable for locating the outlet end (5) of the first cartridge (2) The first hollow piston (40) is fitted with a first stopper component (45) with a circumferential shoulder (46) adapted to fit into the outlet end (5) of the first cartridge (2) and seal it.

[0135] The first hollow piston (40) comprises a star shaped orifice (47) whilst the first stopper component (45) is substantially circular in cross section.

[0136] Similarly, the second hollow piston (41) comprises a star shaped orifice (48) and is fitted with a second stopper component (49). The second stopper component (49) is substantially circular in cross section. However, the inner surface (43a) of the side wall (43) can include ridges (not shown) which enable the second stopper component (49) to form a seal.

[0137] It will be understood by the person skilled in the art that the shape of the orifices (47) and (48) and / or the first and second stopper components (45) and (49) may suitably be varied provided that the stopper (45) and (49) does not form a sealing fit within the orifice (47) and (48).

[0138] In use, when the plunger (6) is depressed within the first cartridge (2) the increase in pressure will force the first stopper component (45) out of the first cartridge(2). This movement allows the first pharmaceutical component (7), usually a fluid, to flow from the first cartridge (2) between the stopper component (45) and the side wall(42) of the piston (40) and through first orifice (47) into the second hollow piston (41). Continued depression of the plunger (6) causes the second stoper component (49) to move axially within the second hollow piston (41) away from the ridges (not shown). This movement causes the second stopper component (49) to lose its seal against the side wall(43) of the second hollow piston (41) allowing the first pharmaceutical component (7) to flow from the first cartridge (2) and first hollow piston (40) past the second stopper component (49) and through orifice (48) into the second cartridge (3) where it mixes with the second pharmaceutical component (11).

[0139] Referring to FIGs. 5 (a) to (d) a pharmaceutical component-mixing delivery assembly (1) comprises a first cartridge (2) and a second cartridge (3), the first cartridge (2) being dimensioned so that it is slidable within the second cartridge (3) from a premixed position to a post-mixed position. An outer casing (97) is provided which houses the first and second cartridges (2) and (3). The first cartridge (2) comprises a body (4) provided with a sealed outlet end (50). The outer casing (97) comprises a sealed plunger end (51) and the plunger (6) protrudes through the sealed plunger end (51) of the outer casing (97). The first cartridge (2) contains a first pharmaceutical component (7). The second cartridge (3) comprises a body (8) provided with an inlet end (9) and an outlet end (10). The second cartridge (3) contains a second pharmaceutical component (11).

[0140] The plunger (6) can include a threaded surface (52) such that the threaded surface (52) is present along a predetermined portion of the length of the plunger (6). The sealed plunger end (51) of the outer casing (97) can include a stopper (53) which includes an orifice (54) through which the plunger (6) passes and a frangible seal (98). The inner surface (55) of the orifice (54) can include a threaded surface (56) which corresponds to and engages with the threaded surface (52) of the plunger (6).

[0141] A plug component (57) separates the first and second cartridges (2) and (3). Said plug component (57) comprises a first seal (58) provided with a hollow needle (59) which extends either side of the first seal (58). A second seal (60) comprises a septum (61) provided with a guide channel (62) which, in use, is adapted to receive the needle (59) extending from the first seal (58).

[0142] In use, when the plunger (6) is turned within the orifice (54) of the stopper (53) in the outer casing (97) the frangible seal (98) is broken and the plunger (6) and the first cartridge (2) are pushed towards the second cartridge (3), causing the first cartridge (2) to disengage from the frangible seal (98). Continued turning of the plunger (6) causes the first cartridge (2) to slide towards the plug component (57) until the needle (59) pierces the sealed outlet end (50) of the first cartridge (2). Continued turning of the plunger (6) causes the needle (59) to pierce the septum (61) allowing the first pharmaceutical component (7), usually a fluid, to flow from the first cartridge (2) through the needle (59) and into the second cartridge (3) where it mixes with the second pharmaceutical component (11). Once the first and second pharmaceutical components (7) and (11) are mixed and the threaded surface (52) of the plunger (6) has passed through the orifice (54), the plunger (6) may be pushed in a conventional manner to administer the medicament solution to a patient.

[0143] Referring to FIGs. 6 and 7 (which includes FIGs. 6 (a) to (d) and FIGs. 7 (a) to (c)) a pharmaceutical component-mixing delivery assembly (1) comprises a first cartridge (2) and a second cartridge (3), the first cartridge (2) being dimensioned so that it is slidable within the second cartridge (3) from a pre-mixed position to a post-mixed position. The first cartridge (2) comprises a body (4) provided with an outlet end (5) and a plunger (6). The first cartridge (2) contains a first pharmaceutical component (7). The second cartridge (3) comprises a body (8) provided with an inlet end (17) and an outlet end (10). The second cartridge (3) contains a second pharmaceutical component (11). A non-invasive valve component (12) separates the first and second cartridges (2) and (3).

[0144] The non-invasive valve component (12) comprises a spigot plug component(63) housed in a piston component (64). The piston component (64) is anchored to the first cartridge (2) by a lip (70). The spigot plug component (63) consists of a T-shaped component (65) with a first end (66) of narrower diameter forming a plug in the outlet end (5) of the first cartridge (2) and a second end (67) of wider diameter adjacent the inlet end (17) of the second cartridge (3). The dimensions of the second end (67) are such that it forms an “annular valve” component (68) with the side wall (69) of piston component(64).

[0145] In use, when the plunger (6) is depressed within the first cartridge (2) the increase in pressure will force the spigot plug component (63) away from outlet end (5) of the first cartridge (2), which creates a conduit (71) between T-shaped component (65) and the side wall (69) of piston component (64) through which the first pharmaceutical component (7), usually a fluid, can flow into the second cartridge (3) where it mixes with the second pharmaceutical component (11).

[0146] Referring to FIGs. 8 and 9 (which includes FIGs. 8 (a) to (c) and FIGs. 9 (a) to (c)) a pharmaceutical component-mixing delivery assembly (1) comprises a first cartridge (2) and a second cartridge (3), the first cartridge (2) being dimensioned so that it is slidable within the second cartridge (3) from a pre-mixed position to a post-mixed position. The first cartridge (2) comprises a body (4) provided with an outlet end (5) and a plunger (6). The first cartridge (2) contains a first pharmaceutical component (7). The second cartridge (3) comprises a body (8) provided with an inlet end (17) and an outlet end (10). The second cartridge (3) contains a second pharmaceutical component (11). A non-invasive valve component (12) separates the first and second cartridges (2) and (3).

[0147] The non-invasive valve component (12) comprises a hollow plug component (72) housed in a piston component (73). The piston component (73) is anchored to the first cartridge (2) by a lip (74). The hollow plug component (72) consists of a stopper (75) provided with a T-shaped conduit (76) such that the inlet end (77) of the conduit is coaxial with the first and second cartridges (2) and (3) and the outlet end (78) of the conduit is perpendicular to the inlet end (77) of the conduit, i.e., diametrical to the stopper (75). The piston component (73) is also T-shaped such that the outlet end (79) of the piston component is of greater diameter than the inlet end (80) of the piston component (73). Thus, the outlet end (78) of the conduit is capable of forming an “annular valve” component (81) with the side wall (82) of piston component (73).

[0148] In use, when the plunger (6) is depressed within the first cartridge (2) the increase in pressure will force the hollow plug component (72) away from outlet end (5) of the first cartridge (2), which opens the T-shaped conduit (76). Thus, the first pharmaceutical component (7), usually a fluid, can flow through the inlet end (77) of the conduit to the outlet end (78) of the conduit and between the side of the hollow plugcomponent (72) and the side wall (82) of piston component (73) into the second cartridge (3) where it mixes with the second pharmaceutical component (11).

[0149] Referring to FIGs. 10 and 11 (which includes FIGs. 10 (a) to (b) and FIGs. 11 (a) to (c)) a pharmaceutical component-mixing delivery assembly (1) comprises a first cartridge (2) and a second cartridge (3), the first cartridge (2) being dimensioned so that it is slidable within the second cartridge (3) from a pre-mixed position to a post-mixed position. The first cartridge (2) comprises a body (4) provided with an outlet end (5) and a plunger (6). The first cartridge (2) contains a first pharmaceutical component (7). The second cartridge (3) comprises a body (8) provided with an inlet end (17) and an outlet end (10). The second cartridge (3) contains a second pharmaceutical component (11). A non-invasive valve component (12) separates the first and second cartridges (2) and (3).

[0150] The non-invasive valve component (12) comprises an elongated piston (83). The piston (83) can include a plurality of external circumferential ribs (84) which form a seal between the side wall (85) of the piston (83) and the inner wall (86) of the second cartridge (3). The piston is also provided with terminal rib (87), comprising a circumferential rib located at the end (88) of the piston (83) nearest to the inlet end (17) of the second cartridge (3).

[0151] The region of the second cartridge (3) that contains the second pharmaceutical component (11) can include an aseptic mixing chamber (89). The length of the piston (83) will be dictated by how far back along the second cartridge (3) it has to move, which will in turn be dictated by the volume required for the mixing chamber (89). In use, as the plunger (6) is depressed and the piston (83) moves towards the inlet end (17) of the second cartridge (3), the mixing chamber (89) does not come into contact with the non-aseptic inner wall (86) of the inlet end (17) of the second cartridge (3) and the sterility of the mixing chamber (89) is maintained at all times.

[0152] FIG. 12 is a cutaway perspective view of another non-invasive valve component (12) for a pharmaceutical component-mixing delivery assembly. The example shown in FIG. 12 is similar to the examiner shown and described with respect to FIGs. 6 and 7. In this example, the non-invasive valve component (12) comprises a piston component (94) that is anchored to the first cartridge (2) by a lip (92). The piston component (94) can include circumferential ribs (95) as defined above. A spigot plug component (93) ishoused in the piston component (94). Similar to as described above, distal to the spigot plug component (93) is positioned a T-shaped conduit (96) into which the spigot plug component (93) can move when the plunger (6) is depressed within the first cartridge (2). The T-shaped conduit (96) is sized such that, when the first cartridge (2) pressure increases to move the spigot plug component (93) distally, an annular valve is created around the spigot plug component (93) and between the plug and the walls of the T- shaped conduit (96). Fluid from first cartridge (2) can then exit the T-shaped conduit (96) through channels (99) formed at the distal end of the piston component (94).

[0153] FIGs. 13A-19 provide example implementations of a needle hub (100) that can be used with any of the aforementioned pharmaceutical component-mixing delivery assemblies (1). The prior disclosure provided various solutions for reconstitution devices. One aspect of those devices is to take the reconstituted medicament and deliver said reconstituted medicament as needed (e. ., by injecting a patient or, more likely, by delivering the fluid from the injector into another medical container or fluid delivery device). More information about delivery mechanisms and needle connections is provided below. FIGs. 13A-19 show an example needle hub (100) that can be used to attach to an outer cartridge (e.g., second cartridge (3)) proximate the outlet end (10) to deliver the medicament.

[0154] Referring now to FIG. 13 A, a needle hub (100) includes a transfer needle (102), which can be attached to or can extend from the needle hub (100). The transfer needle (102) will be positioned such that, once assembled, the transfer needle (102) will be pointed retrograde such that it is pointed toward a pierceable seal of second cartridge (3) (see FIGs. 15A and 15B for reference). FIG. 13B shows the needle hub (100) and the transfer needle (102) assembled. It will be appreciated that the transfer needle (102) can be a separate component from the needle hub (100) and which is co-molded, insert molded, or glued to the needle hub ( 100). In other examples the transfer needle (102) can be a molded spike that is integrated with the needle hub (100).

[0155] The needle hub (100) includes one or more attachment features that allows the hub to attach to a housing (108), as will be described below. The attachment features can be one or more snappers (104) that engage the housing (108), as shown. A snapper (104) is a deflectable extension with a protrusion or tab at one end, and the protrusion or tabcan engage with one or more snapper engagement locations of the housing (108) (see, e.g., FIGs. 14A and 14C). The needle hub (100) also includes a needle connector (106) that can connect to one or more delivery needles (e.g., a delivery needle (120) as in FIG. 15B). The needle connector (106) can be a luer lock connection, a luer slip connection, or the like. The needle connector (106) can be one side of a male-to-male or female-to- female connection that enables the needle hub (100) to fluidly connect the pharmaceutical component-mixing delivery assembly (1) to another delivery device. In some examples, the needle hub (100) can be used in intramuscular injection, and as such the needle connector (106) can be sized and / or shaped to accommodate a delivery needle (120) that can be used for the intramuscular injection, for example and not limitation a 20 to 25 gauge needle. In some examples, the needle hub (100) can be used for subcutaneous injection, and as such the needle connector (106) can be sized and / or shaped to accommodate a delivery needle (120) that can be used for the subcutaneous injection, for example and not limitation a 25 to 30 gauge needle. In some examples, the needle hub (100) can be used in connecting to an intravenous (IV) line, and as such the needle connector (106) can be sized and / or shaped to connect to a connector on the IV line.

[0156] A housing (108) is shown in FIG. 14A. The housing (108) can include visualization windows (110) that can enable an operator to see inside to view the first cartridge (2), second cartridge (3), or the pharmaceutical components therein while reconstitution is being performed. At a distal end of the housing (108) (distal being down in FIG. 14 A), the housing (108) can include longitudinal grooves (see FIG. 14C labeled as grooves (109)) that extend from the end of the housing (108) one or more snapper engagement locations in the housing (108). When the needle hub (100) is being assembled into the distal end of the housing (108), the snappers (104) can slide down a respective longitudinal grooves (109) and snap into place into the one or more snapper engagement locations. The housing (108) can include first snapper engagement locations (112) positioned distally, and second snapper engagement locations (114) positioned more proximally. As will be described in greater detail below, the snappers (104) can be engaged in the first snapper engagement locations (112) when the needle hub (100) is at an initial position. The pressure on the needle hub (100) distally, for example by applying the delivery needle (120) (see FIG. 15B) to the needle connector (106), can cause thesnappers (104) to disengage from the first snapper engagement locations (112) and engage within the second snapper engagement locations (114). At this location, the transfer needle (102) translates proximally as well and extends through the pierceable seal (116) of the second cartridge (3) (also see FIG. 15B for illustration). The snapper engagement locations (112), (114) can be apertures or depressions in the body of the housing (108).

[0157] In other embodiments, the housing (108) can be formed from a translucent or transparent material that does not require visualization windows (110), which could provide the benefit of simplifying the manufacturing processes as well as providing for a more cohesive outer shell. A see-through housing (108) would also allow for the use of a fully wrapped sleeve or sticker that could allow for additional graphics to promote correct usage of the syringe assembly. The fully wrapped sleeve could also be the seal (170) shown in FIG. 22C, for example.

[0158] FIG. 14B shows a housing (108) with a needle hub (100) connected thereto. The needle hub (100) can also include centering guides (105) extending similar to the snappers (104) but do not slide in longitudinal grooves (109). Instead, the centering guides (105) can have an outwardly-deflected bias such that they engage an interior surface of a distal end of the housing (108). FIG. 14C is a cross-sectional view of the housing (108) assembly shown in FIG. 14B. FIG. 14C provides a view of the longitudinal grooves (109) that the one or more snappers (104) can slide through from their first snapper engagement locations (112) to their first snapper engagement locations (114).

[0159] FIG. 15A is a detailed view of a needle hub (100) assembled to a housing (108) prior to attaching a delivery needle (120). The needle hub (100) is positioned near the outlet end (10) of the second cartridge (3), such that the outlet end (10) abuts a stop (118) in the needle hub (100). The transfer needle (102) is positioned toward the pierceable seal (116) of the second cartridge (3). At this position, the one or more snappers (104) can be engaged within their more distal first snapper engagement locations (112) (see FIG. 14B). FIG. 15B is a detailed view of the assembly of FIG. 15A after attaching the delivery needle (120) to the needle hub (100). Axial pressure upon the distal end of the needle hub (100) can cause the needle hub (100) to translate proximally ( / .<?., to the right in the view of FIG. 15B) along a longitudinal axis L-L of the housing (108), moving the snappers(104) through their longitudinal grooves (109) (see FIG. 14C) from the first snapper engagement locations (112) to the second snapper engagement locations (114), and thereby moving the transfer needle (102) through the pierceable seal (116). In some examples, this axial force can be provided by attaching the delivery needle (120) onto the needle connector (106), thereby priming the device to be ready to inject. In other examples, the force of a user inserting the tip of the delivery needle (120) through skin can be sufficient to disengage the one or more snappers (104) from their first snapper engagement locations (112) so as to translate to the second snapper engagement locations (114). In yet other examples, the amount of force required to disengage the one or more snappers (104) from their first snapper engagement locations (112) can be high enough to prevent inadvertent proximal movement of the needle hub (100), and as such a user must provide sufficient, and purposeful force to move the needle hub (100).

[0160] FIG. 16A shows the step of assembling a pharmaceutical component-mixing delivery assembly (1) with a housing (108) comprising a needle hub (100). The pharmaceutical component-mixing delivery assembly (1) can be any of the aforementioned assemblies comprising a first cartridge (2) and a second cartridge (3), and once those cartridges are assembled, they can be inserted into the housing (108) at the opposite end from where the connected needle hub (100) is connected. FIG. 16B shows the pharmaceutical component-mixing delivery assembly (1), housing (108), and needle hub (100) assembled.

[0161] FIG. 17A shows the step of adding an end cap (124) to the assembly shown in FIG. 16B. The end cap (124) can be added to contain the assembled pharmaceutical component-mixing delivery assembly (1) within the housing (108). The end cap (124) includes a plunger aperture (126) that can accept a plunger (6) (see FIG. 18A). FIG. 17B shows the pharmaceutical component-mixing delivery assembly (1), housing (108), and needle hub (100) assembly with the end cap (124) connected.

[0162] FIG. 18A shows the step of adding the plunger (6) to the assembly shown in FIG. 17B. The plunger (6) is inserted into the first cartridge (2) via the plunger aperture (126), and a distal end of the plunger (6) can be attached to a stopper within the first cartridge (2). FIG. 18B shows the pharmaceutical component-mixing delivery assembly (1), housing (108), and needle hub (100) assembly, end cap (124) and plunger (6) allassembled. At the implementation shown in FIG. 18B, the device is ready for adding a delivery needle (120).

[0163] FIG. 19 shows a fully assembled device with a needle hub (100) after delivering a reconstituted medicament using the device. The view clearly shows the location of a snapper (104) having transitioned to a second snapper engagement locations (114). Any of the embodiments described herein can include a safety cap (122) to cover the delivery needle (120), as will be appreciated.

[0164] FIGs. 20-26 show an alternative to the longitudinal, “push” activation of the needle hub (100) shown in FIGs. 13A-19. The examples shown in FIGs. 20-26 instead have a twisting mechanism that causes the transfer needle (102) to translate proximally to extend through the pierceable seal (116) of the second cartridge (3) (also see FIG. 15B for reference). Referring first to FIG. 20, the figure shows a perspective view of a hub housing (108) with an angled groove (132) for engaging with lugs (130) on a needle hub (100) (see FIGs. 21A and 21B for lugs (130)). As shown, the housing (108) can have two angled grooves (132) positioned diametrically opposite each other at the distal end of the housing (108). The one or more angled grooves (132) enable a user to twist the needle hub (100) with respect to the housing (108) in order to move the needle hub (100) proximal to pierce the pierceable seal (116). FIG. 21 A is a cross-sectional view of the needle hub (100) with lugs (130) engageable with the angled grooves (132) of FIG. 20, and FIG. 21B is a top plan view of the needle hub (100) of FIG. 21 A. The example needle hub (100) in FIGs. 21A and 21B have two lugs, first lug (BOA) and second lug (130B), to correspond to a housing (108) having two angled grooves (132). The angled grooves (132) therefore provide a track (labeled as track (150)) through which the lugs (130) move. The angled grooves (132) can be cuts that extend entirely through the body of the housing (108), as shown in FIG. 22A, or the angled grooves (132) can be channels cut superficially into the body of the housing (108).

[0165] FIG. 22A shows a needle hub (100) with lugs (130) engaged in a starting slot (134) of a housing (108) with an angled groove (132). In some examples, the needle hub (100) may be pre-assembled, such that it is configured like that shown in FIG. 22A. As such, the pharmaceutical component-mixing delivery assembly (1) need only be inserted into a proximal end of the housing (108) (see FIG. 16A for illustration). FIG. 22B is aschematic of the track (150) for a twistable needle hub (100) shown in FIG. 22A. The track (150) in FIGs. 22 and 23 have wall snaps (136), (140). In these examples, the track (150) includes a starting slot (134) separated from the angled groove (132) by a first wall snap (136), and includes an ending slot (138) separated from the angled groove (132) by a second wall snap (140). The wall snaps (136), (140) are solid sections of the housing (108) in which the lugs (130) of the needle hub (100) must overcome to transition to the next part of the track (150). For example, in an initial starting position, the needle hub (100) is engaged with the housing (108) such that the one or more lugs (130) are engaged in a starting slot (134). As the user twists the needle hub (100), the one or more lugs (130) will move out of the starting slot (134) and across the first wall snap (136) to engage with the angled groove (132). Moving the one or more lugs (130) across a first wall snap (136) can provide both audible and tactile feedback that the device is being activated for fluid delivery. The user can then continue to twist the needle hub (100) such that the one or more lugs (130) track through the angled groove (132). This movement causes the transfer needle (102) to translate proximally to extend through the pierceable seal (116) of the second cartridge (3) (see FIGs. 15A and 15B for reference). Then the one or more lugs (130) will contact the second wall snap (140) at the end of the angled groove (132). As the user continues to twist the needle hub (100), the one or more lugs (130) will move out of the angled groove (132) and across the second wall snap (140) to engage with the endling slot (138). The ending slot (138) is a location wherein the transfer needle (102) is finally positioned within the pierceable seal (116) (see FIG. 15B for reference).

[0166] FIG. 23A is a proximal-to-distal-end perspective view of a needle hub (100) with inward-facing lugs (130A, BOB). The example assembly shown in FIG. 22A shows a needle hub (100) formed such that it is positioned internal to the distal end of the housing (108). The lugs (first lug (130A) and second lug (130B)) on the needle hub (100) are therefore positioned on the external surface of the hub. In FIG. 23 A, the lugs (first lug (BOA) and second lug (BOB)) of the needle hub (100) are on an inside surface (160) of the hub such that they face inwardly toward the housing (108). As such, the first lug (BOA) and second lug (BOB) will point inwardly and into the track, i.e., angled groove (132), of the housing (108). This design is shown in detail in FIG. 22C, which shows the needle hub (100) of FIGs. 23A and 23B positioned on a housing (108).

[0167] The proximal end of the needle hub (100) terminates at a proximal end surface (161). In some examples, such as seen in FIG. 23 A, the proximal end can include one or more notches (161 A) that give the proximal end surface (161) a wavy contour with one or more ramped / recessed sections. The one or more lugs (130) are provided on sections of the needle hub (100) that are non-recessed. The varying of the contour can be used for various purposes, such as a visual indicator regarding twist of the hub (100) (e.g., direction of twist, twist completion, and the like). In other examples, the proximal end surface can be approximately smooth (i.e., with no notches).

[0168] Referring again to FIG. 23 A and 23B, the needle hub (100) can include a textured grip (162) that enables a user to perform the twisting motion described herein to move the lug(s) (130) through the angled groove (132) of the housing (108). The textured grip (162) can have a variety of designs enabling the user to grip the device to twist, including but not limited to a wavy polygonal pattern (as shown in FIG. 22C and 22D), a rough surface, a gritty surface, and the like. FIG. 22C shows the needle hub of FIGs. 23A and 23B on a housing.

[0169] FIG. 23C shows an example perforated seal (170) that is usable with a twistable needle hub (100). To ensure that the particular injector device has not been previously used, the device can have a perforated seal (170) to act as a tamper-proof indicator. The perforation (172) on the seal (170) can be torn in response to twisting the needle hub (100) to move the lug(s) (130) through the angled groove (132) of the housing (108), as described herein. The perforated seal (170) can also be used as a label, for either providing operational instructions for the device or to provide branding. A proximal edge (174) of the perforated seal (170) can accommodate shapes and features of the housing (108). For example, FIGs. 23C-23E show an example perforated seal (170) having a non-linear proximal edge (174) such that when the perforated seal (170) is rolled (FIG. 23D) onto a hub / housing assembly (FIG. 23E), the proximal edge (174) forms a slanted edge that corresponds to a slanted distal visualization window (110) on the housing (108). For injectors wherein the distal visualization window (110) is not slanted and / or has a horizontal distal edge, the proximal edge (174) of the perforated seal (170) can be straight / horizontal (see FIGs. 23F and 23G). FIGs. 23C-23G each also show cutouts (176) on the perforated seal (170). These cutouts (176) can be provided to avoid an excessof the perforated seal (170) from getting jammed between the needle hub (100) and the housing (108), which may inhibit the user from fully engaging the needle hub (100). In some examples, however, the perforated seal (170) may not include cutouts (176).

[0170] FIG. 24A is a schematic of a different type of track (150) for a twistable needle hub (100). Here, the track (150) does not include the wall snaps (136), (140) and therefore has more of a passive transition as the needle hub (100) is twisted. The example shown has an ending slot (138) that is a vertical track (152). In other words, when the needle hub (100) has been twisted until the one or more lugs (130) enter the ending slot (138), the one or more lugs (130) will track into the vertical track (152). The vertical track (152) can also provide a degree of play, or springiness, to the needle hub (100) as it is being used to deliver a fluid, but a height of the vertical track (152) can be such that the transfer needle (102) (see FIG. 15A) does not retract from the pierceable seal (116) during normal use of delivering fluid through the syringe.

[0171] FIG. 24B is a schematic of a different type of track (150) for a twistable needle hub (100), similar to that of FIG. 24A. Here, the track (150) does not include the wall snaps (136), (140) and therefore has more of a passive transition as the needle hub (100) is twisted. The example shown has a starting slot (134) that is a first vertical track (152A) an ending slot (138) that is a second vertical track (152B). In other words, prior to twisting, the one or more lugs (130) are engaged in the first vertical track (152A) of the starting slot (134). The first vertical track (152A) extends vertically beyond (in both vertical direction) the angled groove (132) at the juncture where the angled groove (132) joins with the starting slot (134), which provides positive feedback to the user that the one or more lugs (130) are engaged with the starting slot (134). When the needle hub (100) has been twisted until the one or more lugs (130) enter the ending slot (138), the one or more lugs (130) will track into the second vertical track (152B). The second vertical track (152B) extends vertically below (i.e., in a direction generally vertically towards the starting slot (134)) the angled groove (132) at the juncture where the angled groove (132) joins with the ending slot (138). The second vertical track (152B) provides positive feedback to the user that the one or more lugs (130) are engaged with the ending slot (138), and can also provide a degree of play, or springiness, to the needle hub (100) as it is being used to deliver a fluid. As with the previous example of FIG. 24A, a heightof the second vertical track (152B) can be such that the transfer needle (102) (see FIG. 15A) does not retract from the pierceable seal (116) during normal use of delivering fluid through the syringe.

[0172] FIG. 25 is a schematic of a different type of track (150) for a twistable needle hub (100). Here, the track (150) does not include the wall snaps (136), (140) and therefore has more of a passive transition as the needle hub (100) is twisted. The example shown has an ending slot (138) that is a horizontal track (154). In other words, when the needle hub (100) has been twisted until the one or more lugs (130) enter the ending slot (138), the one or more lugs (130) will track into the horizontal track (154). The horizontal track (154) can provide a certain amount of rotation for the needle hub (100) once the one or more lugs (130) have seated into the horizontal track (154), but horizontal track (154) is shaped such that the needle hub (100) will be constrained vertically when the needle hub (100) is pushed from its distal end.

[0173] FIG. 26 is a perspective view of a housing (108) with distal threads (142) to engage with a needle hub (100). This example shows an implementation wherein the needle hub (100) can be screwed onto the distal end of the housing (108). FIG. 27A is a cross sectional view of a housing (108) with a distal loading chamfer (156). In this example, the housing (108) can accept a needle hub (100) that is pressed longitudinally into the distal end of the housing (108). The distal loading chamfer (156) can assist in centering the needle hub (100) within the end of the housing (108). FIG. 27B is a cross sectional view of a needle hub (100) with a gas vent (144) and a circumferential seal (146). In some examples, the needle hub (100) can include a circumferential seal (146) to provide an aseptic seal for the pharmaceutical component-mixing delivery assembly (1) within the housing (108). The circumferential seal (146) can include, for example, an elastomer radial seal (e.g., an O-ring), an elastomer linear seal (e.g., a crimp cap), a plastic-to-plastic seal, and the like. In some examples, the pharmaceutical componentmixing delivery assembly (1) can be positioned in the housing (108) / needle hub (100) assembly to be shipped to an end user, and can also be sterilized after assembly. In these examples, the needle hub (100) can include the gas vent (144) to enable pressure equalization between the interior of the housing (108) / needle hub (100) assembly and external environment during sterilization.

[0174] It will also be appreciated that any of the needle hub (100) assemblies described herein and related systems can be used in any environment in which a user needs to reconstitute or resuspend second pharmaceutical component (11) ( .g., a liquid or a solid, such as a powder, medicament) with the help of first pharmaceutical component (7) (e.g., a diluent) within pharmaceutical component-mixing delivery assembly (1). For example, pharmaceutical component-mixing delivery assembly (1) can be stored separately from needle hub (100), and when needed, a user can grab the pharmaceutical componentmixing delivery assembly (1), insert it into needle hub (100) as described herein, reconstitute / resuspend the medicament, and then deliver. As such, it is contemplated that the pharmaceutical component-mixing delivery assembly (1) could be stored in a refrigerated state before being used with needle hub (100). It is also contemplated that the pharmaceutical component-mixing delivery assembly (1) can be stored inside of the needle hub (100). In any case, the systems described herein provide good solutions for emergency care, for example in military use, paramedic or emergency medical services use, and the like.

[0175] FIG. 28 is a flowchart for an example method (2800) for using a syringe assembly. Method (2800) includes connecting (2805) a needle hub to a distal end of a housing. Method (2800) includes inserting (2810) a pharmaceutical component-mixing delivery assembly into a proximal end of the housing. Method (2800) includes securing (2815) the pharmaceutical component-mixing delivery assembly within the housing. Method (2800) includes moving (2820) the needle hub from a first position with respect to the housing to a second position with respect to the housing, such that a transfer needle of the needle hub moves proximally toward the pharmaceutical component-mixing delivery assembly. Method (2800) includes piercing (2825), in response to proximal movement of the transfer needle, a seal of the pharmaceutical component-mixing delivery assembly with the transfer needle.

[0176] FIGs. 29A-29F show steps to fill a pharmaceutical component-mixing delivery assembly (1). The examples shown in FIGs. 29A-29F depict the steps of filling an assembly comprising a first cartridge (2), a second cartridge (3), and the non-invasive valve component (12) shown in and described with respect to FIG. 12. It will be appreciated, however, that other examples of the non-invasive valve component (12)systems described herein can be supplemented in place of the examples shown in FIG. 12. Referring now to the method steps of filling the pharmaceutical component-mixing delivery assembly (1), FIG. 29 A shows the step of adding a spigot plug component (93) to a first cartridge (2). The spigot plug component (93) is inserted to seal the distal end (down in FIG. 29A) of the first cartridge (2). In FIG. 29B, a first pharmaceutical component (7) is added to the first cartridge (2). As described herein, the first pharmaceutical component (7) can be a liquid diluent.

[0177] FIG. 29C shows the step of adding a plunger stopper (128) to the open, proximal end of the first cartridge (2). Because the distal end of the first cartridge (2) includes the spigot plug component (93), inserting the plunger stopper (128) into the first cartridge (2) could cause a positive pressure within the cartridge that could push out the spigot plug component (93). Accordingly, to ensure the spigot plug component (93) is not disengaged from the first cartridge (2) when inserting the plunger stopper (128), the step shown in FIG. 29C can be performed under vacuum. In other words, after adding the first pharmaceutical component (7), the first cartridge (2) can be placed into a vacuum chamber along with the plunger stopper (128) to insert the plunger stopper (128).

[0178] FIG. 29D shows the step of adding a second pharmaceutical component (11) into a distally-sealed second cartridge (3). The second cartridge (3) is sealed by a cartridge cap (115) inserted into the distal end of the second cartridge (3). The cartridge cap (11 ) comprises the aforementioned pierceable seal (116) (see FIGs. 15A and 15B for reference). Since the distal end of the second cartridge (3) is closed, the second pharmaceutical component (11) can be inserted into the rear ( / .<?.. open proximal end) of the second cartridge (3).

[0179] FIG. 29E shows the step of adding a piston component (94) to the first cartridge (2). As described above, a non-invasive valve component (12) can include the piston component (94) and the spigot plug component (93). The non-invasive valve component (12) separates the first and second cartridges (2) and (3). The piston component (94) plus the spigot plug component (93) work as a one-way valve, allowing the first pharmaceutical component (7) to flow distally to mix with the second pharmaceutical component (11) in the second cartridge (3), but preventing the mixed first / second pharmaceutical components to flow proximal back into the second cartridge (3). FIG. 29Esimply shows the step of adding the piston component (94) to the distal end of the first cartridge (2) that already includes the spigot plug component (93) (see FIG. 29A).

[0180] FIG. 29F shows the step of adding the first cartridge (2), with the positioned piston component (94), into the rear ( / .<?., proximal) end of the second cartridge (3). Because the distal end of the second cartridge (3) includes the cartridge cap (115), inserting the first cartridge (2) into the second cartridge (3) could cause a positive pressure to build within the second cartridge (3), making it difficult to insert the first cartridge (2). Accordingly, the step shown in FIG. 29F can be performed under vacuum. In other words, the second cartridge (3) can be placed into a vacuum chamber along with the first cartridge (2) such that the first cartridge (2), with the positioned piston component (94), can be inserted into the rear (z.e., proximal) end of the second cartridge (3). After the step shown in FIG. 29F, the assembled construct shown therein can be inserted into housing (108) assembled with the needle hub (100) (see FIG. 16A).

[0181] FIG. 30 is a flowchart for an example method (3000) for filling a pharmaceutical component-mixing delivery assembly (1) via a rear-fill method. Method (3000) includes inserting (3005) a spigot plug component (90) into a distal end of a first cartridge (2). Method (3000) includes filling (3010) the first cartridge (2), via an open proximal end of the first cartridge (2), with a first pharmaceutical component (7). Method (3000) includes inserting (3015), with the first cartridge (2) in a vacuum, a plunger stopper (128) into the open proximal end of the first cartridge (2) to seal the first pharmaceutical component (7). Method (3000) includes inserting (3020) a cartridge cap (115) onto a distal end of a second cartridge (3), the cartridge cap (115) comprising a pierceable seal (116). Method step (3020) is shown in dashed lines as it is an optional step; the cartridge cap (115) may come pre-loaded on the second cartridge (3). Method (3000) includes filling (3025) the second cartridge (3), via an open proximal end of the second cartridge (3), with a second pharmaceutical component (11). Method (3000) includes positioning (3030) a piston component (94) onto the distal end of the first cartridge (2). Method (3000) includes inserting (3035), with the first cartridge (2) and the second cartridge (3) in a vacuum, the distal end of the first cartridge (2) into the open proximal end of the second cartridge (3) to seal the second pharmaceutical component (11). Method (3000) can end after step (3035), or additional steps can be performed according to the present disclosure.

[0182] FIGs. 31 A-31G show steps to fill a pharmaceutical component-mixing delivery assembly (1). The examples shown in FIGs. 31A-31G depict the steps of filling an assembly comprising a first cartridge (2), a second cartridge (3), and the non-invasive valve component (12) shown in and described with respect to FIG. 12. It will be appreciated, however, that other examples of the non-invasive valve component (12) systems described herein can be supplemented in place of the examples shown in FIG. 12. Referring now to the method steps of filling the pharmaceutical component-mixing delivery assembly (1), FIG. 31A shows the step of adding a spigot plug component (93) to a first cartridge (2). The spigot plug component (93) is inserted to seal the distal end (down in FIG. 31 A) of the first cartridge (2). In FIG. 3 IB, a first pharmaceutical component (7) is added to the first cartridge (2). As described herein, the first pharmaceutical component (7) can be a liquid diluent.

[0183] FIG. 31C shows the step of adding a plunger stopper (128) to the open, proximal end of the first cartridge (2). Because the distal end of the first cartridge (2) includes the spigot plug component (93), inserting the plunger stopper (128) into the first cartridge (2) could cause a positive pressure within the cartridge that could push out the spigot plug component (93). Accordingly, to ensure the spigot plug component (93) is not disengaged from the first cartridge (2) when inserting the plunger stopper (128), the step shown in FIG. 31C can be performed under vacuum. In other words, after adding the first pharmaceutical component (7), the first cartridge (2) can be placed into a vacuum chamber along with the plunger stopper (128), and the plunger stopper (128) can be inserted.

[0184] FIG. 3 ID shows the step of adding a piston component (94) to the first cartridge (2). As described above, a non-invasive valve component (12) can include the piston component (94) and the spigot plug component (93). The non-invasive valve component (12) separates the first and second cartridges (2) and (3). The piston component (94) in combination with the spigot plug component (93) work as a one-way valve, allowing the first pharmaceutical component (7) to flow distally to mix with the second pharmaceutical component (11) in the second cartridge (3), but preventing the mixed first / second pharmaceutical components to flow proximal back into the second cartridge (3). FIG.3 ID simply shows the step of adding the piston component (94) to the distal end of the first cartridge (2) that already includes the spigot plug component (93) (see FIG. 31 A).

[0185] FIG. 3 ID shows the step of adding the first cartridge (2), with the positioned piston component (94), into the rear (i.e., proximal) end of the second cartridge (3). In this example, the distal end / tip of the second cartridge (3) is not covered or closed, so the first cartridge (2), with the positioned piston component (94), can be inserted without positive pressure building in the second cartridge (3). FIG. 3 IF shows inverting the assembly shown in FIG. 3 IE such that the open distal tip of the second cartridge (3) is positioned upwardly. Then, a second pharmaceutical component (11) can be added into the open distal tip of the second cartridge (3). FIG. 31G sows sealing the distal tip of the second cartridge (3) with a cartridge cap (115). After the step shown in FIG. 31G, the assembled construct shown herein can be inserted into housing (108) assembled with the needle hub (100) (see FIG. 16A).

[0186] FIG. 32 is a flowchart for an example method (3200) for filling a pharmaceutical component-mixing delivery assembly (1) via a tip-fill method. Method (3200) includes inserting (3205) a spigot plug component (90) into a distal end of a first cartridge (2). Method (3200) includes filling (3210) the first cartridge (2), via an open proximal end of the first cartridge (2), with a first pharmaceutical component (7). Method (3200) includes inserting (3215), with the first cartridge (2) in a vacuum, a plunger stopper (128) into the open proximal end of the first cartridge (2) to seal the first pharmaceutical component (7). Method (3200) includes positioning (3220) a piston component (94) onto the distal end of the first cartridge (2). Method (3200) includes inserting (3225) the distal end of the first cartridge (2) into a proximal end of a second cartridge (3). Method (3200) includes inverting (3230) the second cartridge (3) such that an open distal end is positioned upwardly. Method (3200) includes filling (3235) the open distal end with a second pharmaceutical component. Method (3200) includes sealing (3240) the second pharmaceutical component within the second cartridge with a cartridge cap. Method (3200) can end after step (3240), or additional steps can be performed according to the present disclosure.

[0187] In any example described herein, the pharmaceutical component-mixing delivery assembly (1) can deliver, for example, a hydrocortisone sodium succinatesodium salt, hydrocortisone phosphate, and / or hydrocortisone acetate. However, as will be appreciated, other active components (such as those listed, supra) can be included. In some examples, the active components can be spray-dried or lyophilized, and that spray- dried or lyophilized product can be placed in the second cartridge (3). In certain examples, there can be advantages to spray drying the active component (e.g., hydrocortisone sodium succinate sodium salt). Spray drying can be a simple, singular process from solution to powder, whereas lyophilization requires additional milling or micronization. Spray drying provides consistent particle size and flow properties, and there is a possibility for particle engineering to adjust size distribution if necessary. The particles made by the spray drying process can be of any size, including nano-, micro-, submicro-, and macro-sized particles. Generally, the particles are between about 0.5 pm to 50 pm in diameter, or between 1 pm and 10 pm in diameter. As such, this disclosure also provides solutions for spray drying the pharmaceutical component (e g., hydrocortisone sodium succinate sodium salt) to include in the second cartridge (3).

[0188] FIG. 33 is a flowchart showing a method 3300 of manufacturing an active pharmaceutical component (e.g., second pharmaceutical component (11)), according to aspects of the present disclosure. Method 3300 can include adding 3305 approximately 1 ,95g hydrocortisone 21-hemi succinate API in to 50mL acetone and stirring until a fully dissolved solution is achieved. Method 3300 can include adding 3310 approximately lOOmL WFI to the fully dissolved solution. Method 3300 can include adding 3315 approximately 0.1N NaOH whilst stirring until a resulting solution having a pH 7.4 is achieved. Method 3300 can include heating 3320 the resulting solution to 25°C under vacuum using a rotary evaporator to remove the acetone, thereby leaving a final solution with a volume of approximately 50mL. Method 300 can include adding 3325 approximately 12.2mg monobasic sodium phosphate anhydrous and approximately 133mg dibasic sodium phosphate to the final solution and stirring to dissolve. Method 3000 can include adjusting 3330 of the final solution the pH to 7.4. Method 3300 can end after the adjusting 3330 step, or additional steps can be performed as described herein or as will be appreciated.

[0189] The steps outlined above were performed to identify the purity produced with such method 3300, and the data is provided in the table shown in FIG. 34. The testedspray-dried powder (labeled as “Current HSS” in the table) was analyzed by RP-HPLC and the purity / impurity profile compared to that of the API, hydrocortisone hemisuccinate and the RLD, Solu-Cortef™ measured in the same chromatographic system. The data (area %), with relevant United States Pharmacopeia (USP) specifications are shown in FIG. 34.

[0190] Compared to the feed API, the “Current HSS” shows increased levels of hydrocortisone (hydrolysis product) and an unknown impurity at RRT 0.57. The impurities seen at RRT 1.13 and RRT 1.53 are derived from the API and are not of concern since the API is supplied as GMP grade suitable for human use. The USP has specifications for hydrocortisone hemisuccinate of not more than 1% of any individual impurity and not more that 2% of total impurities. The API meets these specifications.

[0191] The USP also has specifications for hydrocortisone sodium succinate injection. The specifications allow for not more that 6.7% free hydrocortisone. The specifications do not address impurity levels in the HSS injection preparation. In conclusion, the “Current HSS” meets the required purity specifications.

[0192] The final solution can be spray dried. Spray drying a therapeutic component can be understood to mean a process of subjecting the therapeutic to high temperatures and then cooling the therapeutic, thereby providing an evaporative effect. In the instant case, the final solution of HSS can be spray dried according to the parameters shown in FIG. 35. For example, the HSS can be spray dried at an inlet temperature of from 82°C to 150°C and with an outlet temperature of from 50°C to 90°C, e.g, with an inlet temperature of 147-150°C and with an outlet temperature of 90°C, with an inlet temperature of 111°C and with an outlet temperature of 70°C, with an inlet temperature of 95-99°C and with an outlet temperature of 60°C, with an inlet temperature of 82°C and with an outlet temperature of 50°C, etc. (see FIG. 35). The active pharmaceutical component can be spray dried using nitrogen.

[0193] As stated above, the second pharmaceutical component (11) described within this disclosure can be a solid component (e.g, a powder) that is created, for example and not limitation, via lyophilization or spray-drying. That spray-drying can be accomplished by the features described with respect to FIGs. 33-35.

[0194] FIGs. 36A-36C are cross-sectional views showing use of a syringe assembly.

[0195] Referring to FIG. 36A, the needle hub (100) is connected to a distal end of the housing (108). The first cartridge (2) and the second cartridge (3) are inserted into and secured within a proximal end of the housing (108).

[0196] Referring to FIG. 36B, when the plunger (6) is depressed within the first cartridge (2), the increase in pressure will force the spigot plug component (93) away from outlet end of the first cartridge (2), which opens the conduit (96). Thus, the first pharmaceutical component (7), usually a fluid, can flow through the inlet end of the conduit (96) to the outlet end of the conduit (96) and between the side of the spigot plug component (93) and the side wall of piston component (94) into the second cartridge (3) where it mixes with the second pharmaceutical component (11).

[0197] Referring to FIG. 36C, the needle hub (100) is moved from a first position (see position of the needle hub (100) in FIG. 36B) with respect to the housing (108) to a second position (see position of the needle hub (100) in FIG. 36C) with respect to the housing (108), such that the transfer needle (102) of the needle hub (100) moves proximally toward the pharmaceutical component-mixing delivery assembly. In the present example, the lugs (130) moving along the track (150), which results in a twisting action and the proximal movement. This proximal movement of the transfer needle (102) results in the piercing of the seal (116) of the pharmaceutical component-mixing delivery assembly with the transfer needle (102). The transition between the position shown in FIG. 36B and that shown in FIG. 36C also shows the piston component (94) being pushed further distally by plunger (6). This distal movement of the piston component (94) also drives the reconstituted pharmaceutical component (7, 11) through the transfer needle (102).

[0198] Aspects of the present disclosure can be provided by any of the following clauses.

[0199] Clause 1 : A syringe assembly comprising: a housing; and a needle hub engageable with the housing and movable from a first position with respect to the housing to a second position with respect to the housing, the needle hub comprising: a needle connector positioned such that it faces away from the housing when the needle hub is engaged with the housing; and a transfer needle positioned such that it extends toward the housing when the needle hub is engaged with the housing, the transfer needleconfigured to pierce a seal of a pharmaceutical component-mixing delivery assembly when the needle hub is moved from the first position to the second position.

[0200] Clause 2: The syringe assembly of Clause 1, wherein the second position is located proximally of, and along a longitudinal axis of the housing from, the first position.

[0201] Clause 3: The syringe assembly of Clause 1 or 2, wherein: the housing comprises: a longitudinal groove positioned internally and proximate a distal end of the housing; a first snapper engagement location; and a second snapper engagement location; and the needle hub comprises a snapper extending therefrom, the snapper positionable within the longitudinal groove.

[0202] Clause 4: The syringe assembly of Clause 3, wherein the snapper is engageable with the first snapper engagement location and the second snapper engagement location.

[0203] Clause 5: The syringe assembly of Clause 4, wherein the first snapper engagement location and the second snapper engagement location are indentations in an internal surface of the housing.

[0204] Clause 6: The syringe assembly of Clause 4, wherein the first snapper engagement location and the second snapper engagement location are open apertures in the housing such that at least a portion of the snapper is visible through the first snapper engagement location and the second snapper engagement location.

[0205] Clause 7: The syringe assembly of Clause 1, wherein the needle connector comprises a luer lock connection.

[0206] Clause 8: The syringe assembly of Clause 1, wherein the needle hub is moveable from the first position to the second position responsive to attaching a delivery needle thereto.

[0207] Clause 9: The syringe assembly of Clause 1 , wherein the needle hub is moveable from the first position to the second position responsive to a user advancing the needle hub proximally so as to prime the syringe assembly for medicament delivery.

[0208] Clause 10: The syringe assembly of Clause 1, wherein: the housing comprises an angled groove; the needle hub comprises a lug extending radially and sized to engage the angled groove; and the needle hub is movable from the first position to the second position in response to a twisting motion that enables the lug to track through the angled groove.

[0209] Clause 11 : The syringe assembly of Clause 10, wherein the housing comprises: a starting slot; a first wall snap; a second wall snap; and an ending slot, wherein the angled groove is positioned between the first wall snap and the second wall snap.

[0210] Clause 12: The syringe assembly of Clause 11, wherein the twisting motion causes the lug to pass over the first wall snap and the second wall snap, and that passing over the first wall snap and the second wall snap provides at least one of tactile or audible feedback of a position of the needle hub with respect to the housing.

[0211] Clause 13: The syringe assembly of Clause 1, wherein: the housing comprises distal threads; the needle hub comprises a lug extending radially and sized to engage the distal threads; and the needle hub is movable from the first position to the second position in response to a twisting motion that enables lug to thread through the distal threads.

[0212] Clause 14: The syringe assembly of Clause 1, wherein the needle hub comprises a circumferential seal, the circumferential seal sealing a connection between the needle hub and the housing.

[0213] Clause 15: The syringe assembly of Clause 12, wherein a distal end of the housing comprises a loading chamfer.

[0214] Clause 16: The syringe assembly of Clause 1, wherein the pharmaceutical component-mixing delivery assembly comprises a first cartridge and a second cartridge, the first cartridge and the second cartridge being dimensioned so that they are movable relative to one another such that the first cartridge is slidable within the second cartridge.

[0215] Clause 17: The syringe assembly of Clause 16, wherein the first cartridge comprises a liquid pharmaceutical component, and wherein the second cartridge comprises a solid pharmaceutical component.

[0216] Clause 18: The syringe assembly of Clause 17, wherein the solid pharmaceutical component is a powered component manufactured using a spray-drying technique.

[0217] Clause 19: The syringe assembly of Clause 18, wherein the spray-drying technique is performed according to the process of any one of Clauses 35 to 37.

[0218] Clause 20: A kit comprising the needle hub, the housing, and the pharmaceutical component-mixing delivery assembly of any one of Clauses 16 to 19.

[0219] Clause 21 : A kit comprising the needle hub and the housing of Clause 1.

[0220] Clause 22: A method comprising: connecting a needle hub to a distal end of a housing; inserting a pharmaceutical component-mixing delivery assembly into a proximal end of the housing; securing the pharmaceutical component-mixing delivery assembly within the housing; moving the needle hub from a first position with respect to the housing to a second position with respect to the housing, such that a transfer needle of the needle hub moves proximally toward the pharmaceutical component-mixing delivery assembly; and piercing, in response to proximal movement of the transfer needle, a seal of the pharmaceutical component-mixing delivery assembly with the transfer needle.

[0221] Clause 23 : The method of Clause 22, wherein moving the needle hub from the first position to the second position comprises moving a snapper of the needle hub from a first snapper engagement location to a second snapper engagement location.

[0222] Clause 24: The method of Clause 23, wherein the first snapper engagement location and the second snapper engagement location are indentations in an internal surface of the housing.

[0223] Clause 25: The method of Clause 23, wherein the first snapper engagement location and the second snapper engagement location are open apertures in the housing such that at least a portion of the snapper is visible through the first snapper engagement location and the second snapper engagement location.

[0224] Clause 26: The method of Clause 23 further comprising attaching a delivery needle to a needle connector of the needle hub.

[0225] Clause 27: The method of Clause 26, wherein the needle connector comprises a luer lock connection.

[0226] Clause 28: The method of Clause 26, wherein the needle hub is moveable from the first position to the second position responsive to attaching the delivery needle to the needle connector.

[0227] Clause 29: The method of Clause 22, wherein the needle hub is moveable from the first position to the second position responsive to a user advancing the needle hub proximally so as to prime the pharmaceutical component-mixing delivery assembly for medicament delivery.

[0228] Clause 30: The method of Clause 22, wherein moving the needle hub from the first position to the second position comprises twisting the needle hub with respect to the housing.

[0229] Clause 31 : The method of Clause 30, wherein twisting the needle hub moves a lug of the needle hub along an angled groove disposed within the distal end of the housing.

[0230] Clause 32: The method of Clause 31, further comprising: moving the lug from a starting slot, over a first wall snap, and to the angled groove; and moving the lug from the angled groove, over a second wall snap, and to an endling slot.

[0231] Clause 33 : The method of Clause 32, wherein moving the lug over the first wall snap and the second wall snap provides at least one of tactile or audible feedback of a position of the needle hub with respect to the housing. I’d

[0232] Clause 34: The method of Clause 30, wherein twisting the needle hub moves a lug of the needle hub along threads disposed within the distal end of the housing.

[0233] Clause 35: A method of manufacturing an active pharmaceutical component comprising: adding an active pharmaceutical ingredient to an organic solvent and stirring until a fully dissolved solution is achieved; adding WFI to the fully dissolved solution; optionally adding an inorganic acid (e.g., HC1, or the like) and / or base (e.g., NaOH, sodium bicarbonate, or the like) whilst stirring until a resulting solution having pH 7.4 is achieved; heating the resulting solution to 25°C under vacuum using a rotary evaporator to remove the organic solvent, thereby leaving a final solution having a desired volume; optionally adding a buffer to the final solution and stirring to dissolve; and adjusting the pH of the final solution to 7.4.

[0234] Clause 36: A method of manufacturing an active pharmaceutical component comprising: adding approximately 1.95g hydrocortisone 21-hemi succinate API in to 50mL acetone and stirring until a fully dissolved solution is achieved; adding approximately lOOmL WFI to the fully dissolved solution; adding approximately 0.1N NaOH whilst stirring until a resulting solution having a pH 7.4 is achieved; heating the resulting solution to 25°C under vacuum using a rotary evaporator to remove the acetone, thereby leaving a final solution with a volume of approximately 50mL; adding approximately 12.2mg monobasic sodium phosphate anhydrous and approximately133mg dibasic sodium phosphate to the final solution and stirring to dissolve; and adjusting of the final solution the pH to 7.4.

[0235] Clause 37: The method of Clause 36, wherein the step of manufacturing the active pharmaceutical component further comprises spray drying the final solution using nitrogen.

[0236] Clause 38: The method of Clause 36, further comprising spray drying the final solution at an inlet temperature of from 82°C to 150°C, and with an outlet temperature of from 50°C to 90°C.

[0237] Clause 39: A method for filling a pharmaceutical component-mixing delivery assembly comprising: inserting a spigot plug component into a distal end of a first cartridge; filling the first cartridge, via an open proximal end of the first cartridge, with a first pharmaceutical component; inserting, with the first cartridge in a vacuum, a plunger stopper into the open proximal end of the first cartridge to seal the first pharmaceutical component; filling the second cartridge, via an open proximal end of the second cartridge, with a second pharmaceutical component; positioning a piston component onto the distal end of the first cartridge; and inserting, with the first cartridge and the second cartridge in a vacuum, the distal end of the first cartridge into the open proximal end of the second cartridge to seal the second pharmaceutical component.

[0238] Clause 40: The method of Clause 39, further comprising, after the inserting the plunger stopper step: inserting a cartridge cap onto a distal end of a second cartridge, the cartridge cap comprising a pierceable seal.

[0239] Clause 41: A method for filling a pharmaceutical component-mixing delivery assembly comprising: inserting a spigot plug component into a distal end of a first cartridge; filling the first cartridge, via an open proximal end of the first cartridge, with a first pharmaceutical component; inserting, with the first cartridge in a vacuum, a plunger stopper into the open proximal end of the first cartridge to seal the first pharmaceutical component; positioning a piston component onto the distal end of the first cartridge; inserting the distal end of the first cartridge into a proximal end of a second cartridge; inverting the second cartridge such that an open distal end is positioned upwardly; filling the open distal end with a second pharmaceutical component; and sealing the second pharmaceutical component within the second cartridge with a cartridge cap.

[0240] It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present disclosure which will be limited only by the appended claims.

[0241] Ranges may be expressed herein as from “about” one particular value, and / or to “about” another particular value. When such a range is expressed, also specifically contemplated and considered disclosed is the range from the one particular value and / or to the other particular value unless the context specifically indicates otherwise. Similarly, when values are expressed as approximations, by use of the antecedent “about” or “approximately,” it will be understood that the particular value forms another, specifically contemplated embodiment that should be considered disclosed unless the context specifically indicates otherwise. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint unless the context specifically indicates otherwise. The term “about” or “approximately” as used herein when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of ±20%, ±10%, ±5%, ±1%, ±0.5%, or ±0.1% from the specified value, as such variations are appropriate to perform the disclosed methods.

[0242] “Optional” or “optionally” means that the subsequently described event, circumstance, or material may or may not occur or be present, and that the description includes instances where the event, circumstance, or material occurs or is present and instances where it does not occur or is not present.

[0243] The phrase “and / or,” as used herein in the specification and in the claims, should be understood to mean “either or both” of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Other elements may optionally be present other than the elements specifically identified by the “and / or” clause, whether related or unrelated to those elements specifically identified unless clearly indicated to the contrary. Thus, as a non-limiting example, a reference to “A and / or B,” when used in conjunction with open-ended language such as “comprising” can refer, in some embodiments, to A without B (optionally including elements other than B); in another embodiments, to B without A (optionally including elements other thanA); in yet another embodiments, to both A and B (optionally including other elements); etc.

[0244] The following reference numbers are used in this detailed disclosure.

Claims

CLAIMS1. A syringe assembly comprising: a housing; and a needle hub engageable with the housing and movable from a first position with respect to the housing to a second position with respect to the housing, the needle hub comprising: a needle connector positioned such that the needle connector faces away from the housing when the needle hub is engaged with the housing; and a transfer needle positioned such that the needle connector extends toward the housing when the needle hub is engaged with the housing, the transfer needle configured to pierce a seal of a pharmaceutical componentmixing delivery assembly when the needle hub is moved from the first position to the second position.

2. The syringe assembly of Claim 1, wherein the second position is located proximally of, and along a longitudinal axis of the housing from, the first position.

3. The syringe assembly of Claim 1 or 2, wherein: the housing comprises: a longitudinal groove positioned internally and proximate a distal end of the housing; a first snapper engagement location; and a second snapper engagement location; and the needle hub comprises a snapper extending therefrom, the snapper positionable within the longitudinal groove.

4. The syringe assembly of Claim 3, wherein the snapper is engageable with the first snapper engagement location and the second snapper engagement location.

5. The syringe assembly of Claim 4, wherein the first snapper engagement location and the second snapper engagement location are indentations in an internal surface of the housing.

6. The syringe assembly of Claim 4, wherein the first snapper engagement location and the second snapper engagement location are open apertures in the housing such that at least a portion of the snapper is visible through the first snapper engagement location and the second snapper engagement location.

7. The syringe assembly of Claim 1, wherein the needle connector comprises a luer lock connection.

8. The syringe assembly of Claim 1, wherein the needle hub is moveable from the first position to the second position responsive to attaching a delivery needle thereto.

9. The syringe assembly of Claim 1, wherein the needle hub is moveable from the first position to the second position responsive to a user advancing the needle hub proximally so as to prime the syringe assembly for medicament delivery.

10. The syringe assembly of Claim 1, wherein: the housing comprises an angled groove; the needle hub comprises a lug extending radially and sized to engage the angled groove; and the needle hub is movable from the first position to the second position in response to a twisting motion that enables the lug to track through the angled groove.

11. The syringe assembly of Claim 10, wherein the housing comprises: a starting slot; a first wall snap; a second wall snap; and an ending slot,wherein the angled groove is positioned between the first wall snap and the second wall snap.

12. The syringe assembly of Claim 11, wherein the twisting motion causes the lug to pass over the first wall snap and the second wall snap, and that passing over the first wall snap and the second wall snap provides at least one of tactile or audible feedback of a position of the needle hub with respect to the housing.

13. The syringe assembly of Claim 1, wherein: the housing comprises distal threads; the needle hub comprises a lug extending radially and sized to engage the distal threads; and the needle hub is movable from the first position to the second position in response to a twisting motion that enables lug to thread through the distal threads.

14. The syringe assembly of Claim 1, wherein the needle hub comprises a circumferential seal, the circumferential seal sealing a connection between the needle hub and the housing.

15. The syringe assembly of Claim 12, wherein a distal end of the housing comprises a loading chamfer.

16. The syringe assembly of Claim 1, wherein the pharmaceutical componentmixing delivery assembly comprises a first cartridge and a second cartridge, the first cartridge and the second cartridge being dimensioned so that they are movable relative to one another such that the first cartridge is slidable within the second cartridge.

17. The syringe assembly of Claim 16, wherein the first cartridge comprises a liquid pharmaceutical component, and wherein the second cartridge comprises a solid pharmaceutical component.

18. The syringe assembly of Claim 17, wherein the solid pharmaceutical component is a powered component manufactured using a spray-drying technique.

19. The syringe assembly of Claim 18, wherein the spray-drying technique is performed according to the process of any one of Claims 35 to 37.

20. A kit comprising the needle hub, the housing, and the pharmaceutical component-mixing delivery assembly of any one of Claims 16 to 19.

21. A kit comprising the needle hub and the housing of Claim 1.

22. A method comprising: connecting a needle hub to a distal end of a housing; inserting a pharmaceutical component-mixing delivery assembly into a proximal end of the housing; securing the pharmaceutical component-mixing delivery assembly within the housing; moving the needle hub from a first position with respect to the housing to a second position with respect to the housing, such that a transfer needle of the needle hub moves proximally toward the pharmaceutical component-mixing delivery assembly; and piercing, in response to proximal movement of the transfer needle, a seal of the pharmaceutical component-mixing delivery assembly with the transfer needle.

23. The method of Claim 22, wherein moving the needle hub from the first position to the second position comprises moving a snapper of the needle hub from a first snapper engagement location to a second snapper engagement location.

24. The method of Claim 23, wherein the first snapper engagement location and the second snapper engagement location are indentations in an internal surface of the housing.

25. The method of Claim 23, wherein the first snapper engagement location and the second snapper engagement location are open apertures in the housing such that at least a portion of the snapper is visible through the first snapper engagement location and the second snapper engagement location.

26. The method of Claim 23 further comprising attaching a delivery needle to a needle connector of the needle hub.

27. The method of Claim 26, wherein the needle connector comprises a luer lock connection.

28. The method of Claim 26, wherein the needle hub is moveable from the first position to the second position responsive to attaching the delivery needle to the needle connector.

29. The method of Claim 22, wherein the needle hub is moveable from the first position to the second position responsive to a user advancing the needle hub proximally so as to prime the pharmaceutical component-mixing delivery assembly for medicament delivery.

30. The method of Claim 22, wherein moving the needle hub from the first position to the second position comprises twisting the needle hub with respect to the housing.

31. The method of Claim 30, wherein twisting the needle hub moves a lug of the needle hub along an angled groove disposed within the distal end of the housing.

32. The method of Claim 31, further comprising: moving the lug from a starting slot, over a first wall snap, and to the angled groove; andmoving the lug from the angled groove, over a second wall snap, and to an endling slot.

33. The method of Claim 32, wherein moving the lug over the first wall snap and the second wall snap provides at least one of tactile or audible feedback of a position of the needle hub with respect to the housing.

34. The method of Claim 30, wherein twisting the needle hub moves a lug of the needle hub along threads disposed within the distal end of the housing.

35. A method of manufacturing an active pharmaceutical component comprising: adding an active pharmaceutical ingredient to an organic solvent and stirring until a fully dissolved solution is achieved; adding WFI to the fully dissolved solution; optionally adding an inorganic acid and / or base whilst stirring until a resulting solution having pH 7.4 is achieved; heating the resulting solution to 25°C under vacuum using a rotary evaporator to remove the organic solvent, thereby leaving a final solution having a desired volume; optionally adding a buffer to the final solution and stirring to dissolve; and adjusting the pH of the final solution to 7.4.

36. A method of manufacturing an active pharmaceutical component comprising: adding approximately 1.95g hydrocortisone 21-hemi succinate API in to 50mL acetone and stirring until a fully dissolved solution is achieved; adding approximately lOOmL WFI to the fully dissolved solution; adding approximately 0. IN NaOH whilst stirring until a resulting solution having a pH 7.4 is achieved; heating the resulting solution to 25°C under vacuum using a rotary evaporator to remove the acetone, thereby leaving a final solution with a volume of approximately 50mL;adding approximately 12.2mg monobasic sodium phosphate anhydrous and approximately 133mg dibasic sodium phosphate to the final solution and stirring to dissolve; and adjusting of the final solution the pH to 7.4.

37. The method of Claim 36, wherein the step of manufacturing the active pharmaceutical component further comprises spray drying the final solution using nitrogen.

38. The method of Claim 36, further comprising spray drying the final solution at an inlet temperature of from 82°C to 150°C, and with an outlet temperature of from 50°C to 90°C.

39. A method for filling a pharmaceutical component-mixing delivery assembly comprising: inserting a spigot plug component into a distal end of a first cartridge; filling the first cartridge, via an open proximal end of the first cartridge, with a first pharmaceutical component; inserting, with the first cartridge in a vacuum, a plunger stopper into the open proximal end of the first cartridge to seal the first pharmaceutical component; filling a second cartridge, via an open proximal end of the second cartridge, with a second pharmaceutical component; positioning a piston component onto the distal end of the first cartridge; and inserting, with the first cartridge and the second cartridge in a vacuum, the distal end of the first cartridge into the open proximal end of the second cartridge to seal the second pharmaceutical component.

40. The method of Claim 39, further comprising, after the inserting the plunger stopper step: inserting a cartridge cap onto a distal end of a second cartridge, the cartridge cap comprising a pierceable seal.

41. A method for filling a pharmaceutical component-mixing delivery assembly comprising: inserting a spigot plug component into a distal end of a first cartridge; filling the first cartridge, via an open proximal end of the first cartridge, with a first pharmaceutical component; inserting, with the first cartridge in a vacuum, a plunger stopper into the open proximal end of the first cartridge to seal the first pharmaceutical component; positioning a piston component onto the distal end of the first cartridge; inserting the distal end of the first cartridge into a proximal end of a second cartridge; inverting the second cartridge such that an open distal end is positioned upwardly; filling the open distal end with a second pharmaceutical component; and sealing the second pharmaceutical component within the second cartridge with a cartridge cap.

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