Chemical Mixing System

Abstract

The present invention provides a drug mixing system 10 for mixing a drug formulation 110a stored in a vial 110, such as a powder for reconstitution or a drug concentrate, with a liquid stored in a separate reservoir 120, and then transferring the dissolved or diluted drug formulation 110b to a receiving device 200, such as a nebulizer 201, for delivery to a target site or for subsequent administration. The drug mixing system 10 aims to simplify and improve both the mixing and transfer steps by, among other things, reducing the number of steps required and limiting the risk of contamination and / or leakage of the dissolved or diluted drug formulation 110b. To this end, the drug mixing system 10 uses the overpressure generated when transferring the liquid from the reservoir 120 to the vial 110 with the aid of a piston 125 and then locking the piston 125 in place. The aforementioned overpressure relief by expelling the dissolved or diluted formulation 110b from the vial 110 through the outlet port 130 of the drug mixing system 10 into the receiving device 200 is preferably activated automatically upon connection of the drug mixing system 10 and the receiving device 200.

Description

[Technical Field]

[0001] The present invention relates to a drug mixing system, and in particular to a drug mixing system that facilitates and simplifies the transfer of a freshly prepared formulation (e.g., a dry powder formulation of a drug intended for reconstitution) to a target administration site and / or receiving device such as a nebulizer in a short time prior to use. [Background technology]

[0002] Drugs intended for administration to a patient are often provided either as a dry powder (e.g., lyophilized) or in liquid form (e.g., liquid concentrate or solubilized). Prior to administration, these drugs in powder or liquid form typically require reconstitution or dilution with a pharmaceutically acceptable liquid or vehicle (e.g., a solvent such as water for injection purposes), which is provided in a container separate from the drug. Reconstitution of a drug for administration to a patient should be performed with as little loss as possible and under sterile conditions by transferring a pharmaceutically acceptable liquid to the drug and mixing the drug with the pharmaceutically acceptable liquid.

[0003] Many prior art systems require numerous handling steps to prepare the system for mixing and injection before use, such as breaking an ampoule containing the injectable medium or piercing a rubber closure on a vial or bottle filled with the injectable medium with a needle, aspirating the injectable medium into a syringe, transferring the aspirated medium to a vial containing the formulation, and often several additional steps to mix the drug with the injectable medium and, in most cases, dissolve it therein (e.g., creating physical agitation by shaking the vial and / or moving the drug-vehicle mixture back and forth between the vial and the syringe). If the resulting formulation is then intended for injection into a patient (as opposed to, e.g., some testing device), it is often necessary to exchange the needle attached to the syringe before injection, because the diameter of the needle used for convenient handling and mixing is often larger than that which allows for easy and painless injection.

[0004] Furthermore, in prior art systems where there is no direct connection between the drug-containing vial and the vehicle-containing syringe, the transfer of either the injectable liquid and / or the formulation resulting from mixing the drug with said injectable liquid can introduce air into the system and, consequently, the introduction of airborne microorganisms.

[0005] Furthermore, many users or patients are reluctant to prepare injectable formulations, for example, by opening glass ampoules and / or manually handling multiple needles. Thus, compliance with medications that require the above-described "prepare just before use" procedure is often low, and / or the preparation steps outlined above must be performed by medically trained staff or caregivers. In summary, prior art systems, particularly the multiple steps they require, are not only susceptible to contamination, but also not very user-friendly.

[0006] Attempts to overcome some of the above challenges have been made, particularly for medications intended for subsequent injection using a needle and syringe. For example, U.S. Patent Application Publication No. 20130046270 (herein "US270") or International Publication No. 2021094548 (herein "WO548") describe a mixing and injection system that includes an adapter having an opening adapted to hold two containers: a "drug container" (e.g., a glass vial) containing a formulation, and a "liquid container" containing a liquid for dissolving or diluting the formulation. The adapters of both US270 and WO548 include two movably engageable subunits that enable an activation step of the adapter or an activation step on the adapter, thereby puncturing and opening an initially closed drug container (and possibly both the drug container and the liquid container). That is, activation is achieved by pressing the two subunits of the adapter together or toward each other. Once activated, the liquid can then be transferred from the liquid container to the drug container without the formulation and / or the liquid for dissolving or diluting it coming into contact with the user's hands and without the user being exposed to the released needle tip during this transfer step.

[0007] US270 only provides for one-way liquid flow from a vial-type liquid container, i.e., a "liquid vial," to a vial-type drug container, i.e., a "drug vial," driven by the vacuum often present in such drug vials (e.g., vials of lyophilized drug products). In other words, when the closure of the drug vial of US270 is pierced and opened, the negative pressure within said drug vial draws liquid from the liquid vial. In contrast, WO548 uses a syringe instead of the liquid vial of US270 as the liquid container, thereby providing the option of two-way flow between the drug container and the liquid container, which may be advantageous, for example, for drugs with solubility issues (e.g., poorly soluble drugs) that can benefit from a more thorough mixing process. Furthermore, unlike US 270, which requires the dissolved pharmaceutical composition to be drawn into a separate injection syringe (i.e., a third container attached or attachable to their adapter, which is then removed from the adapter for injection), WO 548 already uses a syringe as a liquid container, thus allowing not only the front-to-back mixing described above, but also (i) a more compact and less material-consuming mixing and injection system, and (ii) easier injection by simply attaching an injection needle to the outlet port of the adapter, without the need to remove the syringe from the adapter. In other words, the syringe of the mixing and injection system described in WO 548 serves both as a liquid container containing a liquid for dissolving or diluting the formulation and as the actual injection syringe.

[0008] However, both the US270 and WO548 systems are expressly adapted to prepare a formulation for injection by dissolving or diluting a drug in a separately stored liquid and then injecting it into the recipient's body (e.g., into a human patient) using a syringe needle. Neither US270 nor WO548 mentions other means of applying or using the freshly dissolved / diluted formulation, or how users of their systems might be further supported if the application mode is not injection, e.g., if the freshly dissolved / diluted formulation must be transferred, preferably without contamination or product loss, to a different site of action or to a receiving device other than a syringe.

[0009] Thus, this can present additional challenges for users, especially those experiencing mobility and / or visual impairments.

[0010] Similar considerations apply to U.S. Patent Application Publication No. 20040030285 (herein "US285"). This document also describes a drug delivery device for mixing and delivering drugs by injection, specifically a drug delivery system that uses overpressure to inject a dissolved formulation into human skin. The overpressure is generated within the drug vial when diluent (e.g., 1 mL) is forced from a diluent cartridge into the drug vial, thereby compressing the ambient air therein. However, to preserve the overpressure, the device user must manually depress the inserted liquid cartridge while simultaneously manually pressing a release mechanism to move the injection needle into the skin. Furthermore, to prevent the injection of compressed air into the skin, the exit opening (the injection needle in US285) must be positioned at an angle of approximately 90° relative to the longitudinal central axis of the drug vial, and the dissolved formulation is delivered to this exit opening via a tortuous flow path / tube. This setting increases both the dead volume through which the formulation is lost and can cause problems with formulations that are not solutions, such as emulsions or suspensions. Furthermore, US 285 teaches that the pressure can only be adjusted by changing the liquid cartridge (e.g., less liquid), which means that flexibility is limited with standardized pre-filled cartridges.

[0011] It is therefore an object of the present invention to provide a device that avoids these drawbacks of the prior art, for example, by providing a drug mixing system or device that is easy to use (e.g., intuitive and preferably one-handed), has low susceptibility to tampering, or is even tamper-proof, and requires few components (i.e., low material consumption). This, in turn, provides for reduced drug product waste and improved flexibility when working with standardized pre-filled drug and / or liquid containers, and minimizes the risk of contamination during dissolution or dilution, preferably under sterile conditions, of the drug product prior to administration. Summary of the Invention

[0012] In a first aspect, the present invention provides a pharmaceutical mixing system (10) for dissolving or diluting a pharmaceutical preparation (110a) stored in a vial (110) prior to use, the pharmaceutical mixing system (10) comprising an adapter (100) adapted to hold a vial (110) containing the pharmaceutical preparation (110a), and a reservoir (120) for containing a liquid (120a) for dissolving or diluting the pharmaceutical preparation (110a), the reservoir (120) comprising a housing (124) and a piston (125) sealingly movable within the housing, the adapter (100) comprising a vial attachment opening (111) adapted to hold the vial (110), a reservoir attachment opening (121) adapted to hold the reservoir (120), an outlet port (130), and an internal adapter fluidly connecting the vial attachment opening (111) and the reservoir attachment opening (121) to the outlet port (130). and a liquid retaining means (145) adapted to block the flow of at least the dissolved or diluted formulation (110b) through the outlet port (130), wherein the adapter (100) comprises a piston locking means (126) adapted to lock the position of the piston (125) when a predetermined amount of liquid is transferred from the reservoir (120) into the vial (110) by pressing the piston (125) into the housing (124), thereby creating and storing an overpressure. The drug mixing system (10) is adapted to expel or transfer the dissolved or diluted formulation (110b) from the vial (110) through the outlet port (130) when a liquid releasing means (155, 255) is actuated using the overpressure created by pressing the piston (125) into the housing (124).

[0013] In a second aspect, the present invention relates to an adapter (100) for a drug mixing system (10) according to the first aspect of the invention.

[0014] In a third aspect, the present invention relates to a method for preparing a dissolved or diluted formulation (110b), optionally a drug solution, from a formulation (110a) stored in a vial (110) using a drug mixing system (10) according to the first aspect of the present invention, more particularly the method comprising: a) providing a pharmaceutical mixing system (10) according to a first aspect of the present invention; b) transferring a predetermined amount of liquid from the reservoir (120) into the vial (110) by pushing the piston (125) into the housing (124) while the liquid retaining means (145) blocks the flow of at least the dissolved or diluted formulation (110b) through the outlet port (130), thereby creating an overpressure and a mixture of the formulation (110a) and the liquid; c) once a predetermined amount of liquid has been transferred from the reservoir (120) to the vial (110), locking the piston (125) in place with the piston locking means (126), thereby storing the overpressure created in step b; d) dissolving or diluting the mixture of formulation (110a) and liquid resulting from steps b) and c) to the desired extent, optionally assisting this dissolving or diluting process by vibrating the drug mixing system (10); e) using the stored overpressure generated in steps b) and c) to expel or transfer the dissolved or diluted formulation (110b) from the vial (110) through the outlet port (130) by actuating the liquid expelling means (155, 255), thereby forcing the piston (125) into the housing (124) and locking the piston (125) in place.

[0015] Further objects, aspects, useful embodiments, applications, beneficial effects, and advantages of the present invention will become apparent based on the description of the invention, the following examples, figures, and claims. [Brief explanation of the drawings]

[0016] The following examples and figures serve to illustrate the invention in exemplary embodiments. However, they should not be understood as limiting the scope of the invention. Any reference signs used in the claims or throughout the specification should not be construed as limitations to the embodiments depicted in any of the figures. Further details of the figures follow in the detailed description section below.

[0017] Furthermore, it should be understood that the figures provided herein represent depictions of the devices and components described herein and are simplified to an extent that allows for a description of said devices and components in terms of their function, effect, and interrelationships, but do not necessarily depict every small detail that may additionally be present in a device or system of the present invention. Thus, the description may include details that are not necessarily all shown in the drawings.

[0018] 1A-1E are cross-sectional front views of an exemplary embodiment of a drug mixing system (10) according to a first aspect of the present invention, more specifically, a sealed-type drug mixing system (10a), in its normal, upright operating position. A vial (110) and a reservoir (120) are positioned side-by-side within an adapter (100 / 100a) with their respective central longitudinal axes "A" and "B" aligned parallel (see FIG. 1E). The adapter (100 / 100a) of the system, which includes two adapter subunits (101, 102), is shown in both its rest position (FIG. 1A; the vial (110) and reservoir (120) are sealed; the subunits are slightly separated) and its actuated position (FIG. 1B; the vial (110) and reservoir (120) are pierced; the subunits are moved toward each other). FIG. 1C shows the system while piston (125) is being inserted into reservoir (120) housing (124), here in the form of a pharmaceutical cartridge (120b) having reservoir lid (122), thereby generating overpressure in vial (110). Movement of the piston is guided by piston guide means (127 / 127a / 127b). Piston (125) includes a piston head (125a) on which a user can place their finger to apply pressure to move the piston, and a stopper (125b) at its lower end facing the liquid (120a) in housing (124). FIG. 1D then shows that the inserted piston (125) is locked in place with piston locking means (126), here in the form of an engaging hook (126a) that captures piston head (125a), thereby accumulating the generated overpressure. The drug mixing system (10a) is provided at its lower end with a connecting means (160), here a male connecting means (160m) that allows connection to the receiving device (200). The septum (131) is attached to the peripheral wall (132) of the outlet port (130), here by, for example, crimping with a metal closure, and functions as a liquid retaining means (145) that blocks the flow of liquid from the outlet port (130).As shown in FIG. 1E, the outlet port (130 / 132) is positioned vertically aligned below the vial (110) and vial piercing cannula (113) (the central longitudinal axis "A" of the vial and the central longitudinal axis "P" of the outlet port are aligned, not angled), allowing for unimpeded, overpressure-driven, gravity-assisted, and non-tortuous flow from the vial (110) to the outlet port (130). FIGS. 1A-1E show embodiments in which the outlet port (130 / 132) protrudes or overhangs slightly from the bottom wall of the adapter (100 / 100a). In alternative embodiments, the downstream end of the outlet port (130) may also be arranged to be flush with the bottom wall of the drug mixing system (10 / 10a). A sleeve-like, dimensionally stable stabilizing wall (170) with dedicated areas (105) for the placement of the four fingers of a human hand surrounds or encases the adapter (100 / 100a) as well as the vial (110) and reservoir (120), thereby preventing the two from bending or being removed from the adapter (100 / 100a). In addition to the piston guide means (127), here in the form of a piston guide groove (127a), the stabilizing wall (170) also forms at its upper end a piston fixing means (129), here in the form of a small hook-like structure, which prevents the piston (125) from being lost, separated, or removed from the reservoir housing (124).

[0019] 2A shows a cross-sectional side view or oblique rear view of an exemplary embodiment of a receiving device (200) according to the first aspect of the present invention, more specifically a receiving device in the form of a nebulizer (201), and even more specifically a vibrating mesh nebulizer (202) having a nebulization chamber (203) and a mesh (204), or a receiving device in the form of a perforated disk. The receiving device (200a) shown in FIG. 2A is adapted for combination and interaction with the seal-type drug mixing system (10a) shown in FIGS. 1A-1E by means of a dedicated lid (270a) with an inlet opening (210) that not only allows access to the nebulization chamber (203) but is also equipped with a liquid discharge means (255) in the form of a septum piercing means (230) having a piercing tip (231). The aforementioned septum piercing means (230) is located at the center of a spoked-wheel-shaped portion (220) located within the inlet opening (210). In Figure 2A, the septum piercing means (230) is provided as a solid piercing pin (230b). Alternatively, as shown in Figures 3A-3C, the septum piercing means (230) may be provided as a cannula or hollow needle (230a). A raised wall (271) disposed on the top of the lid (270 / 270a) and surrounding the inlet opening (210) functions as a female mating means (260f) into which the lower end of the drug mixing system (10a), which functions as a corresponding male mating means (160m), can be inserted or nested.

[0020] 2B is a tilted top view of an exemplary embodiment of a lid (270 / 270a) of a receiving device (200a) similar to that shown in FIG. 2A, providing a better view of the exemplary spoked-wheel-shaped portion (220) that supports the septum piercing means (230 / 230b) at its center and allows liquid to pass through the inlet opening (210) and past the ribs (220a) of the spoked-wheel portion (220) into the nebulization chamber (203; not shown). In the illustrated embodiment, the raised wall (271) that surrounds the inlet opening (210) and serves as the female mating means (260f) of the receiving device (200a) is shaped as a complete circle.

[0021] 3A-3C show that the lower end of the drug mixing system (10a), which functions as the male connecting means (160m), is inserted or nested into the corresponding female connecting means (260f) of the receiving device (200a / 201 / 202), thereby causing the piercing tip (231) of the septum piercing means (255 / 230 / 230a) to pierce or protrude into the septum (131) (or in other words, actuating the liquid discharging means (255)), thereby discharging the piston (125) into the reservoir. 1A-1E illustrate how the seal-type drug mixing system (10a) shown in FIGS. 1A-1E interacts with a receiving device (200a) in the form of a vibrating mesh nebulizer (201 / 202) shown in FIG. 2A when diluted or dissolved formulation (110b) is released from vial (110) through outlet port (130) into receiving device (200a / 201 / 202) using overpressure created by forcing into vial housing (124). When the septum (131) is punctured, both the outlet port (130 / 132) and the receiving device inlet opening (210) are aligned perpendicularly, rather than at an angle to each other, below the vial (110) and vial puncture cannula, allowing unimpeded, overpressure-driven, gravity-assisted, non-tortuous flow from the vial (110) through the outlet port (130 / 132) and inlet opening (210) and into the receiving device (200), here the nebulization chamber (203).

[0022] Figures 4A-4D are similar to Figures 1A-1E, but instead show cross-sectional front views of an alternative exemplary embodiment of the drug mixing system (10) of the first aspect of the present invention, namely, a valve-type drug mixing system (10b), in which the liquid retaining means (145) is provided in the form of a switch valve (150) and the liquid discharging means (155, 255) is provided in the form of a switch valve operating means (156).

[0023] Figure 5 shows a receiving device 200b adapted for combination and interaction with the valve-type drug mixing system 10b shown in Figures 4A-4D. The receiving device 200b is essentially the same as that shown in Figure 2A (e.g., nebulizer 201, more specifically vibrating mesh nebulizer 202), but has a different lid 270b that does not have a septum piercing means 230 within its inlet opening 210.

[0024] 6A and 6B show cross-sectional side views of an exemplary embodiment of the valve-type drug mixing system 10b shown in FIGS. 4A-4D interacting with the receiving device 200b shown in FIG. 5. The elevated wall 271 on the receiving device lid 270b surrounding the receiving device's inlet opening 210 serves as the female connecting means 260f of the receiving device 200b into which the lower end of the drug mixing system 10b, which serves as the corresponding male connecting means 160m, can be inserted or nested to connect the drug mixing system to the receiving device. Furthermore, the inlet opening 210 of the receiving device lid 270b is shaped and sized to receive the drug mixing system's outlet port 130 / 132, which protrudes or overhangs the bottom wall of the adapter 100 / 100b. Additionally, the valve-type drug mixing system (10b) exhibits a liquid dispensing means (155) in the form of a push button-like protrusion (156a) extending from the male connection means (160m) of the adapter and functioning as a switch valve operating means (156). When the male connecting means (160m) of the drug mixing system (10b) is inserted or nested into the corresponding female connecting means (260f) of the receiving device (200b / 201 / 202), the switch valve operating means (156 / 156a) is gradually pressed inward by the female connecting means (260f), thereby shifting the valve from a first valve position that blocks the flow of liquid through the outlet port (130; see FIG. 6A) to a second valve position that allows the flow of liquid through the outlet port (130; see FIG. 6B), thus expelling the dissolved or diluted formulation (110b) from the vial (110), through the outlet port (130), and into the receiving device (200b / 201 / 202), here the nebulization chamber (203), using the overpressure created by forcing the piston (125) into the reservoir housing (124).When the switch valve (150) is actuated by the switch valve operating means (156 / 156a), both the outlet port (130 / 132) and the receiving device inlet opening (210) are aligned perpendicularly, rather than at an angle to each other, below the vial (110) and vial puncture cannula, allowing unimpeded, overpressure-driven, gravity-assisted, and non-tortuous flow from the vial (110) through the outlet port (130 / 132) and inlet opening (210) and into the receiving device.

[0025] 7A-7C show side views of an exemplary embodiment of a drug mixing system (10) according to a first aspect of the present invention, in which a sleeve-like, dimensionally stable stabilizing wall (170) surrounds or encases most of the adapter (100), vial (110), and reservoir (120). Dedicated locations (105, 105′) for resting one or more fingers during use are provided in the stabilizing wall (170). For example, four concave recesses (105) on one side are provided for resting the four fingers of a human hand (particularly during the piston movement step), as well as patterned ledges (105′), one on either side of the drug mixing system, for resting one or two fingers (particularly during the adapter activation step). While Figures 7A and 7B show the piston projections (127b) shaped to "sandwich" corresponding piston guide grooves (127a) by flanges (127b' / 127") on either side of the stabilizing wall (170), the piston projections (127b) in Figure 7C are shaped with flanges (127') only on or against the inside surface of the stabilizing wall (170). Figure 7B shows that the inserted piston (125) is locked in place by piston locking means (126), here in the form of an engaging hook (126a) that captures the piston head (125a).

[0026] Figures 8A-8C show side views of an exemplary embodiment of a drug mixing system 10 according to a first aspect of the present invention, such as the drug mixing system 10 shown in Figure 7C, in use. Figures 8A and 8B illustrate activation steps of the adapter 100 using one or both hands 300, respectively, with the fingers resting on dedicated areas shaped as patterned shelves 105', one hand on either side of the drug mixing system, and the thumb pressed against the flat bottom or lower edge of the adapter 100 (the adapter is covered by the outer stabilizing wall 170 in the depiction). Alternatively, relative to the finger placement shown in Figure 8A, a user could place the drug mixing system 10 between their spread index and middle fingers. FIG. 8C shows the position of the hand (300) during the insertion step of the piston (125), i.e., when said piston is pushed into the housing (124) of the reservoir (120), with the thumb resting / pressing on the piston (125) or its head (125a) and the four fingers resting or abutting on their respective designated areas shaped as four concave depressions (105), thus holding the drug mixing system (10) firmly in the hand (300) but not directly exerting any potentially displacing force on the vial (110) and / or reservoir (120).

[0027] 9A-9C show side views of an exemplary embodiment of the drug mixing system (10) according to the first aspect of the present invention, in which the piston locking means (126) is provided in the form of an engaging hook (126a), more particularly in the form of a plurality of engaging hooks (126a, 126a', 126a") that capture the piston head (125a). In the embodiment shown, there are three engaging hooks (126a, 126a', 126a") spaced apart to allow for stepwise insertion and locking of the piston (125) in three stages, thus transferring 1 / 3, 2 / 3 or 3 / 3 of the liquid (120a) contained in the reservoir (120) into the vial (110). The respective insertion depths of the pistons (125) are marked on the outside of the stabilizing wall (170) of the adapter by visible markings (173), here shown in the form of raised markings. Unlike Figures 1, 3, 4, and 6-8, in which engagement hooks 126a are molded in / within piston guide grooves 127a, the embodiment shown in Figures 9A-9D shows engagement hooks 126a, 126a', 126a" extending from piston guide rails 127aa. Piston 125, and more specifically piston head 125a, includes corresponding piston guide notches 127bb shaped to "sandwich" piston guide rails 127aa while a user presses piston 125 down into housing 124. Furthermore, in the embodiment shown in Figures 9A-9C, piston (125) is not locked into place by trapping the top surface of the piston head (where the user places their finger) under one of the engagement hooks (126a, 126a', 126a"); instead, a resilient or springy tail hook (126b), which is fixedly associated with or forms an integral part of piston head (125a), is trapped under the engagement hook. This detail is shown in more detail in the cross-sectional side view of Figure 9D. The user receives tactile and / or audio feedback when piston (125) is inserted deep enough for tail hook (126b) to spring into one of the engagement hooks (126a, 126a', 126a").The slight "click" sensation and / or sound, as well as the downwardly sloping shape of the engagement hooks (126a, 126a', 126a"), ensure that the piston (125) can only be inserted further downwards, but cannot unintentionally slide back. Thus, any overpressure generated in the vial (110) due to the transfer of the liquid (120a) contained in the reservoir (120), here in the form of a pharmaceutical cartridge (120b), can be stored. As can also be seen in FIG. 9D, there are two sets of both piston guide means (127 / 127a / 127b) and piston locking means (126, 126a, 126a', 126a", 126b), one on one side of the adapter (100) and piston head (125a). As can be further seen in Figure 9D, a raised wall 271 located on the top of the receiving device lid 270 (receiving device not shown here) serves as a male mating means 260m that is inserted into a corresponding female mating means 160f on the lower end of the drug mixing system 10a. As can be seen in Figure 9B, the outlet port 130 and its peripheral wall 132 are positioned vertically aligned below the vial 110 rather than at an angle to each other, allowing for unimpeded, overpressure-driven, gravity-assisted, non-tortuous flow from the vial 110 toward the outlet port 130. The embodiment shown in FIGS. 9A-9C further shows a small indicator window 172 that typically visually indicates to the user whether the adapter 100 is in its activated position (i.e., whether the two adapter subunits (not shown in detail in FIG. 9) have moved toward each other, thus piercing the vial 110 and reservoir 120). The indicator window 172 may, for example, turn green when the adapter 100 is activated. Alternative embodiments to those shown in FIGS. 9A-9D may include, for example, different graduations (e.g., ½ and ½ instead of ⅓), printed or engraved markings instead of raised ones, and / or tactile activation indicators instead of color-changing ones.

[0028] 10A-10D illustrate further exemplary embodiments of a drug mixing system 10 according to the first aspect of the present invention, particularly its use in conjunction with a receiving device 200 in the form of a nebulizer 201, more particularly a vibrating mesh nebulizer 202. Typically, a user is provided with both the nebulizer 201 / 202 and the drug mixing system 10 sterile-packaged in a package 400 in pre-assembled form, optionally in the form of a starter kit, as shown in FIG. 10A. The nebulizer 201 / 202 is then typically reused, with a fresh, separately packaged drug mixing system 10 provided to freshly prepare the formulation 110b before each use. As shown in FIG. 10A, a user removes the protective packaging 400 that houses the drug mixing system 10, including the adapter 100 of the drug mixing system 10, the vial 110 for storing the drug formulation 110a, and the reservoir 120 for storing a liquid 120a for dissolving or diluting the drug formulation 110a, in a sterile environment until use. The vial 110 and reservoir 120 are already inserted and securely held within the adapter to prevent or reduce the risk of contamination and / or misassembly. In the first handling step, shown at the top of FIG. 10B, the user actuates the adapter 100, i.e., by pushing the lower end of the drug mixing system 10 and the bottom 115 of the vial 110, causing the two adapter subunits (not shown in detail in FIG. 10) to move toward each other. Actuation is noticeable by tactile and / or acoustic feedback (a small "click" sensation and / or sound) and a color change in indicator window 172. Piston 125 is then inserted into reservoir housing 124 by manually pushing piston head 125a and moving the piston into either first through-hole 126c only or second through-hole 126c' to transfer one-half or both halves of liquid 120a from reservoir 120 into vial 110, respectively (described in further detail below) and generate a corresponding overpressure.The user can then visually assess when the formulation 110a stored in the vial 110 has dissolved or diluted to the desired degree using the sight glass 171, as shown in the center of FIG. 10C (which shows the formation of a solution). Optionally, the process can be aided by gently shaking or swirling the drug mixing system 10. The lower end of the drug mixing system 10 is then placed on the lid 270 of the nebulizer 201 / 202 and gently pressed down (e.g., by pressing again against the bottom 115 of the vial 110) to activate the liquid release means, thereby using the generated overpressure to expel or transport the dissolved or diluted formulation 110b from the vial 110 through the outlet port 130. Activation of the liquid dispensing means is perceptible via tactile and / or acoustic feedback (a small "click" sensation and / or sound) and visually via the viewing window (171) in the vial (110). After transferring the dissolved or diluted formulation (110b) from the vial (110) to the nebulizer (201 / 202), the drug mixing system can be removed, and the nebulizer is ready for inhalation, as shown in FIG. 10D. As further shown in the center of FIG. 1D, in the illustrated embodiment, the outlet port (130), and more specifically its downstream end, is flush with the bottom wall of the drug mixing system (10).

[0029] As further shown in FIGS. 10A-10D, the illustrated embodiment includes an alternative piston locking means (126), i.e., a piston locking means provided in the form of a snap-fit ​​locking mechanism (126c), or a plurality thereof. Here, the adapter's stabilizing wall (170) presents two through-holes (126c, 126c') into which a corresponding piston locking protrusion (126d) of appropriately adapted size and shape located on the piston head (125a) can snap-fit ​​when it reaches the through-hole position during piston (125) insertion. See, for example, the top of FIG. 10C. The snap-fit ​​can be recognized via tactile and / or acoustic feedback, a small "click" sensation and / or sound. Additionally, the piston locking protrusion (126d) on the piston head (125a) may also be a different color from the material of the stabilizing wall (170), visually indicating that it snaps into one of the two through-holes (126c, 126c'), as shown in FIG. 10C. The provision of two through holes means that it is possible to insert and lock the piston in half steps, i.e., to transfer one half or both halves of the liquid (120a) contained in the reservoir (120) into the vial (110). definition

[0030] The following expressions used herein should generally be interpreted as outlined in this section, unless explanation provides a different meaning in a specific context.

[0031] The terms "a," "an," or "the" do not exclude a plurality; that is, these singular forms should be understood to include plural referents unless the context clearly indicates or requires otherwise. In other words, all references to singular features or limitations in this disclosure shall include the corresponding plural features or limitations, and vice versa, unless expressly stated otherwise or clearly implied otherwise by the context in which the reference is made. Thus, the terms "a," "an," or "the" have the same meaning as "at least one" or "one or more," unless otherwise defined.

[0032] The phrases "one embodiment," "an embodiment," "a specific embodiment," and the like mean that the particular feature, property, or characteristic, or particular group or combination of features, properties, or characteristics, referenced in connection with the respective phrase, is present in at least one embodiment of the invention. The appearances of these phrases in various places throughout this specification do not necessarily refer to the same embodiment. Furthermore, the particular features, properties, or characteristics may be combined in any suitable manner in one or more embodiments.

[0033] Terms such as "about," "approximately," "about," "essentially," or "substantially" are meant to compensate for variations accepted in the relevant technical field and inherent in each product (e.g., pharmaceutical industry and pharmaceutical products), such as differences in content due to manufacturing variability and / or product degradation over time. Terms relating to attributes or values ​​include the exact attribute or exact value, as well as any attribute or value normally considered to be within a normal range or variation accepted in the relevant technical field.

[0034] The term "comprise" should be interpreted in an open and inclusive sense, such as "including, but not limited to." The phrases "substantially consisting of" or "essentially consisting of" mean that no additional ingredients other than those listed are added.

[0035] The term "non-releasable" is understood to mean that the respective connected components of the adapter or drug mixing system are not releasable or separable from one another without the need for force and / or without destroying the adapter or drug mixing system.

[0036] The term "injectable liquid" is understood as any fluid that can flow and is suitable and safe for parenteral administration to a patient or animal.

[0037] The terms "drug," "agent," "active pharmaceutical ingredient" (API), and the like are used interchangeably herein and refer to a compound or combination of compounds that is pharmaceutically active against an undesirable condition.

[0038] The term "pharmaceutically acceptable" means that the material is generally safe, non-toxic, and exhibits no biologically or otherwise undesirable properties that would prevent or preclude its use in humans, making the material useful in the preparation of pharmaceutical compositions.

[0039] Terms specifying position, orientation, or direction, such as left, right, front, rear, back, top, bottom, above, below, etc., should be understood with reference to the orientation of the disclosed devices or components thereof under normal operating conditions (i.e., intended use), typically from the perspective of a user.

[0040] A single unit may fulfill the functions of several features recited in the claims. DETAILED DESCRIPTION OF THE INVENTION

[0041] In a first aspect, the present invention provides a pharmaceutical mixing system (10) for dissolving or diluting a pharmaceutical preparation (110a) stored in a vial (110) prior to use, the pharmaceutical mixing system (10) comprising an adapter (100) adapted to hold a vial (110) containing the pharmaceutical preparation (110a), and a reservoir (120) for containing a liquid (120a) for dissolving or diluting the pharmaceutical preparation (110a), the reservoir (120) comprising a housing (124) and a piston (125) sealingly movable within the housing, the adapter (100) comprising a vial attachment opening (111) adapted to hold the vial (110), a reservoir attachment opening (121) adapted to hold the reservoir (120), an outlet port (130), and an internal adapter fluidly connecting the vial attachment opening (111) and the reservoir attachment opening (121) to the outlet port (130). and a liquid retaining means (145) adapted to block the flow of at least the dissolved or diluted formulation (110b) through the outlet port (130), wherein the adapter (100) comprises a piston locking means (126) adapted to lock the position of the piston (125) when a predetermined amount of liquid is transferred from the reservoir (120) into the vial (110) by pressing the piston (125) into the housing (124), thereby creating and storing an overpressure. The drug mixing system (10) is adapted to expel or transfer the dissolved or diluted formulation (110b) from the vial (110) through the outlet port (130) when a liquid releasing means (155, 255) is actuated using the overpressure created by pressing the piston (125) into the housing (124).

[0042] The drug mixing system 10 according to this first embodiment may be provided in at least two different designs, referred to herein as (a) a seal-type drug mixing system 10a or (b) a valve-type drug mixing system 10b. The difference between these two designs resides primarily in their liquid retention means 145 and their liquid release means 155, 255: (i) how the flow of liquid, e.g., the flow of dissolved or diluted formulation 110b, through the outlet port 130 is prevented or inhibited during overpressure generation, and (ii) how the flow is subsequently enabled once the liquid is ready to be discharged or transferred through the outlet port 130.

[0043] For the sealed type drug mixing system (10a), a liquid retaining means (145) is provided in the form of a septum (131) covering the outlet port (130), and a liquid releasing means (155, 255) is provided in the form of a septum piercing means (230) whereby, upon actuation, the septum (131) is pierced by the septum piercing means (230) and the dissolved or diluted formulation (110b) is expelled or transferred from the vial (110) through the outlet port (130) using an overpressure created by forcing the piston (125) into the housing (124). The septum (131) can be provided in a variety of sealing materials, such as those commonly used to close vials containing lyophilized drugs (e.g., rubber, silicone, blends of these two with polytetrafluoroethylene (PTFE), chlorobutyl, bromobutyl, etc.), and can be secured to the peripheral wall (132) forming the outlet port (130) in any manner that prevents separation from said outlet port (130) under pressure (e.g., crimped with a metal closure or firmly secured by heat staking).

[0044] With respect to the valve-type drug mixing system (10b), the liquid retaining means (145) is provided in the form of a switch valve (150), the internal adapter channel (140) and the switch valve (150) at least allowing selective fluid communication between the vial (110) and the reservoir (120) while blocking fluid communication to the outlet port (130) when in valve position 1, and selective fluid communication between the vial (110) and the outlet port (130) while blocking fluid communication to the reservoir (120) when in valve position 2. The liquid discharge means (155, 255) is provided in the form of a switch valve operating means (156) adapted to enable selective fluid connection and adapted to place the switch valve (150) in valve position 2 upon actuation, whereby, when the switch valve (150) is placed in valve position 2, the dissolved or diluted formulation (110b) is expelled or transferred from the vial (110) through the outlet port (130) using overpressure generated by forcing the piston (125) into the housing (124). In one embodiment, the switch valve (150) is a three-way switch valve having three openings for selectively enabling fluid connection between the vial mounting opening (111), the reservoir mounting opening (121), and the outlet port (130). In a further embodiment, the switch valve (150) is rotatable or shiftable, i.e., can be operated using a rotatable button or push button (156) to move the switch valve (150) from position 1 to position 2. Optionally, in certain embodiments, the switch valve (150) may also be adapted to switch to a third position, valve position 3, to block the fluid connection between the vial mounting opening (111), the reservoir mounting opening (121), and the outlet port (130).

[0045] As shown in the figure, the piston 125 has (i) a piston head 125a at its upper end and outside the reservoir housing 124, i.e., a portion where a user of the drug mixing system 10 can place his or her finger to apply pressure and move the piston into the housing, and (ii) a stopper 125b at its lower end, facing the liquid 120a stored in the housing 124, that ensures sealed movement of the piston 125 within the housing 124 so that the liquid 120a can be forced from the reservoir 120 into the vial 110, creating overpressure. According to the present invention, the piston 125 is pressed toward and into the housing, not vice versa. This is advantageous insofar as the piston 125, and in particular its piston head 125a, can be more easily modified than the housing 124. The housing 124 often requires specific, fixed dimensions to ensure that a defined volume is contained therein. In one of the preferred embodiments, the piston head (125a) is adapted to allow physical interaction with both the piston locking means (126) and the piston guiding means (127) of the adapter, as described in more detail below.

[0046] In a further preferred embodiment, the piston head (125a) is adapted to be attachable to the piston (125), for example as a snap-on or slip-on "crown cap", thereby allowing standardized pistons, such as those used in commercially available syringes or pharmaceutical cartridges, to be customized for use with the drug mixing system (10) according to the first aspect of the present invention.

[0047] Further, in accordance with the present invention, outlet port 130 and its peripheral wall 132 are positioned vertically aligned with and below vial 110 (rather than at an angle to one another) to allow unimpeded, overpressure-driven, gravity-assisted, and tortuous flow from vial 110 toward outlet port 130. As used herein, vertical alignment refers to when vial 110 exhibits a central longitudinal axis "A" and outlet port 130 exhibits a central longitudinal axis "P," with the two axes being aligned with one another (as exemplarily shown in FIG. 1E) or when axes "A" and "P" are at least parallel to one another and offset from one another by a short distance of no more than 5 mm, preferably no more than 2 mm. Any flow guide structure disposed between the vial (110) and the exit port (130), such as the vial puncture cannula (113) shown in FIG. 1E, should also preferably be positioned below the vial (110) in vertical alignment with the vial (110), and should be straight, non-collapsible, and non-tortuous so as not to impede the overpressure-driven, gravity-assisted, non-tortuous flow from the vial (110) to the exit port (130).

[0048] Further system details for both the seal-type drug mixing system 10a and the valve-type drug mixing system 10b are provided below.

[0049] The drug mixing system 10 according to the first aspect of the present invention can be employed for a wide variety of purposes requiring the preparation of a fresh liquid formulation immediately prior to use. Examples include, but are not limited to, drugs that are hydrolytically sensitive and therefore must be stored dry, but are administered in liquid form. The dissolved or diluted formulation 110b formed within the vial 110 can be applied directly to the user's skin from the drug mixing system 10, for example. However, more commonly, the dissolved or diluted formulation 110b formed within the vial 110 for administration is transferred from said vial 110 via an outlet port 130 to a receiving device 200 for receiving the dissolved or diluted formulation 110b. The receiving device 200 can be any suitable administration device for liquid formulations, for example, an injection device such as a syringe driver (also known as a perfusion pump) or a nebulizer.

[0050] In one embodiment, the receiving device (200) is a nebulizer (201). In a more specific embodiment, the receiving device (200) is a vibrating mesh nebulizer (202) having a nebulization chamber (203; or drug reservoir) and a mesh (204; or perforated plate). Here, the dissolved or diluted formulation (110b) from the vial (110) is transferred into or received by the nebulization chamber (203) of the vibrating mesh nebulizer (202), as shown, for example, in FIG. 3C or FIG. 6B.

[0051] The liquid releasing means (155, 255) can be provided, optionally as an integral part, as part of the receiving device (200) or the adapter (100), meaning that in embodiments including the receiving device (200), the dissolved or diluted formulation (110b) is then released from the vial (110) upon interaction of the drug mixing system (10) with the receiving device (200).

[0052] For purposes of connecting the drug mixing system 10 to the receiving device 200, the adapter 100 and the receiving device 200 include connecting means 160 and connecting means 260, respectively, where reference numeral "160" refers to the connecting means provided on the adapter 100 and "260" refers to the connecting means provided on the receiving device 200. Such connecting / connecting means 160, 260 may include, for example, plug-in connections, snap-fit ​​mechanisms, etc. In one embodiment, the connecting means 160 and connecting means 260 are adapted such that, upon connection, the drug mixing system 10 and the receiving device 200 form a leak-proof connection. This is preferable to prevent both leakage of the dissolved or diluted formulation 110b and contamination of the surfaces and / or hands 300 of a user of the drug mixing system 10 and the receiving device 200 during transfer of the dissolved or diluted formulation 110b.

[0053] In one embodiment, the adapter 100 includes a male connecting means 160m that is insertable into the female connecting means 260f of the receiving device 200. For example, as shown in Figures 3A-3C or 6A-6B, in one embodiment, a raised wall 271 disposed on the top of the lid 270 and surrounding the inlet opening 210 of the receiving device serves as the female connecting means 260f into which the lower end of the drug mixing system 10, more specifically the lower end of the adapter 100, can be inserted or nested, which serves as the corresponding male connecting means 160m. The exact shape of the raised wall 271 on the lid 270 in the aforementioned embodiment is not important, so long as it matches the size and shape of the corresponding lower end of the adapter, allowing said end to be inserted or nested snugly into the shape of the raised wall 271. The rising wall 271 may, for example, be shaped as a complete circular wall (e.g., as in FIG. 2B or 7C) or may be open on one side (i.e., generally U-shaped). The lid 270 on the receiving device 200 may be provided in a removable form, for example, as a hinged lid as shown in FIGS. 2A-2B, 3A-3C, 5, 6A-6B, or 9C, so that both the lid 270 and the rising wall 271 thereon can be easily customized to each drug mixing system 10 intended for use with the receiving device 200.

[0054] In that regard, it should be understood that in some embodiments, the connecting / connected means (160, 260) may be a feature that provides functionality in addition to functioning as a connecting means. For example, as shown in FIG. 6B, the peripheral wall (132) that defines the outlet port (130) can extend from the adapter (100 / 100b) and be shaped and sized to fit into the respective shaped and sized inlet opening (210) of the receiving device (200) like a "plug." Thus, the peripheral wall (132) and inlet opening (210) provide male / female connecting means (160m, 260f) in addition to the male / female connecting means (160m, 260f) provided in the form of the lower end of the adapter (100 / 100b) and the upper elevated wall (271) of the receiving device lid (270) that surrounds the inlet opening (210), respectively. At the same time, the aforementioned peripheral wall (132) may also be part of an adapter (100 / 100b) to which the septum (131) is attached (e.g., secured by a crimped metal closure or by heat staking) to block the outlet port (130) in the seal-type drug mixing system (10a).

[0055] It should be further understood that the adapter 100 and the receiving device 200 may also comprise two or more connecting means 160 and connecting means 260 for connecting the drug mixing system 10 to the receiving device 200. For example, the adapter 100 and the receiving device 200 may comprise the above-mentioned "plug-in" connections (i) between the peripheral wall 132 forming the outlet port 130 and the inlet opening 210 of the receiving device 200, and (ii) between the lower end of the adapter 100 and the raised wall 271 on the lid 270 surrounding the inlet opening 210, in addition to the above-mentioned "plug-in" connections. Additionally, the adapter 100 and the receiving device 200 may comprise additional snap-fit ​​connections. In certain embodiments, one or both of these connections may be non-releasable (e.g., a very tight snap-fit ​​that can only be released by destruction of the connecting means). This may be advantageous for disposable drug mixing systems (10), for example, to prevent users from attempting to reuse them.

[0056] In one preferred embodiment, the connecting means 160 and the connected means 260 are adapted so that when they are connected, i.e., when the adapter 100 of the drug mixing system 10 is connected to the receiving device 200, the liquid releasing means 155, 255 is actuated. This means that, upon connection, the septum 131 of the seal-type drug mixing system 10a is pierced and opened, or the switch valve 150 of the valve-type drug mixing system 10b is switched from its position 1 (flow at the outlet port is blocked) to its position 2 (flow at the outlet port is enabled). In a further preferred embodiment, this actuation occurs automatically. That is, the connecting means 160 and the connectable means 260 are adapted in such a way that, upon connection of the seal-type drug mixing system 10a with the receiving device 200, the septum puncturing means 230 is adapted to automatically puncture the septum 131, or, upon connection of the valve-type drug mixing system 10b with the receiving device 200, the switch valve 150 is automatically placed in valve position 2 (i.e., without requiring any further steps to be dynamically performed by an operator or user), preferably through physical interaction of the device components. For example, in one embodiment, upon connection of the valve-type drug mixing system 10b with the receiving device 200, the switch valve 150 is automatically placed in valve position 2, via physical interaction of the connecting means 160 and / or the connectable means 260 with the switch valve operating means 156 of the adapter 100b.

[0057] In certain embodiments, the aforementioned switch valve operating means (156) is part of the adapter (100b) of the valve-type drug mixing system (10b). In a further specific embodiment, for example, as shown in Figures 6A and 6B, the switch valve operating means (156) is provided in the form of a push-button-like protrusion (156a) protruding from the male connecting means (160m) of the adapter (100b), which is insertable into the female connecting means (260f) of the receiving device (200), and when the male connecting means (160m) is inserted into the female connecting means (260f), the protruding switch valve operating means (156a) is pushed into the male connecting means (160m), thereby moving the switch valve (150) to valve position 2, and the dissolved or diluted formulation (110b) is expelled or transferred from the vial (110) to the receiving device (200) via the outlet port (130) using overpressure.

[0058] In one embodiment, as shown in Figures 6A and 6B, the protruding switch valve operating means 156a and / or the female mating means 260f of the adapter 100b of the receiving device 200 are also provided with an inclined or sloped surface to facilitate controlled and stable movement of the protruding switch valve operating means 156a when pressed into the male mating means 160m. In certain embodiments, the protruding switch valve operating means 156a of the adapter 100b is covered by a protective wall or cover (not shown) adapted and positioned to prevent premature and / or unintentional movement of the protruding switch valve operating means 156a prior to connecting the drug mixing system 10 to the receiving device 200. This is beneficial even if a user grips or holds the drug mixing system 10 by the outlet port 130 end, as long as the user does not unintentionally move the valve 150 with their fingers. In a further embodiment, the receiving device (200) is provided with a valve operating pin (256; not shown), and when the male connecting means (160m) of the adapter (100b) is inserted into the female connecting means (260f) of the receiving device (200), the protruding switch valve operating means (156a) is pushed into the male connecting means (160m) by the valve operating pin (256), thereby moving the switch valve (150) to valve position 2, and the dissolved or diluted formulation (110b) is expelled or transferred from the vial (110) to the receiving device (200) via the outlet port (130) using overpressure.

[0059] As mentioned above, the liquid discharge means (155, 255) can be provided, optionally as an integral part, as part of the receiving device (200) or the adapter (100). In one embodiment of the seal-type drug mixing system (10a), i.e., when the liquid discharge means (155, 255) is provided in the form of a septum piercing means (230), the septum piercing means (230) is provided, optionally as an integral part, as part of the receiving device (200). In certain embodiments, for example, as shown in FIG. 2A, the septum piercing means (230) is located at the center of a spoke-wheel-shaped portion (220) located at the inlet opening (210) of the receiving device, i.e., the opening through which the dissolved or diluted formulation (110b) is received. In a more specific embodiment, the spoked wheel-shaped portion (220) is shaped and / or positioned within the entrance opening (210) of the receiving device (200) such that the puncturing tip (231) of the septum puncturing means (230) does not overhang or protrude from the surface of the outer casing (240) of the receiving device (200). This is beneficial insofar as it reduces the risk of injury to the user and reduces the risk of material other than skin becoming caught on the puncturing tip, either during use and / or storage. In one embodiment (not shown), the spoked wheel-shaped portion (220) is concavely shaped, with the center or hub of the spoked wheel-shaped portion (220) located deeper within the entrance opening (210) than the outer periphery of the wheel, causing the puncturing tip (231) to protrude below the surface of the outer casing (240). Alternatively, the same tip-projecting effect can be achieved with a flat or horizontal spoke-wheel-shaped portion (220; i.e., wheel hub and circumference in the same plane) by positioning the entire spoke-wheel-shaped portion (220) deeper within the inlet opening (210), as shown, for example, in FIG. 2A.

[0060] In one embodiment of the seal-type drug mixing system 10a, the septum puncturing means 230 is provided in the form of a septum puncturing cannula 230a, or a hollow needle, or a so-called "spike" (such as, for example, the Rowe Spike offered by Mediplast or the Mini-Spike offered by B. Braun Melsungen). Depending on the characteristics of the septum 131, such as thickness, mechanical properties of the septum material, etc., the liquid expelled through the outlet port 130 upon puncturing the septum 131 may then pass completely through said septum puncturing cannula / hollow needle / spike 230a, or partially through and partially along the outside of the septum puncturing cannula / hollow needle 230a if the cannula / needle forms a larger opening through the septum 131.

[0061] In an alternative embodiment, the septum puncture means 230 is provided in the form of a solid septum puncture pin 230b, i.e., without a bore or channel for fluid flow through its center. Depending on the nature of the septum 131, the septum puncture pin 230b may puncture a hole in the septum 131 or open and widen an existing opening, such as a sealed slit, through the septum 131.

[0062] Optionally, the septum piercing means (230) can include structural features on its outer periphery that increase the opening pierced in the septum (131) as the septum piercing means (230) is inserted. For example, the outer periphery of the septum piercing means (230) can include a set of spike-ribs (232) that flare from the tip of the septum piercing means (230) toward the stem. This can be beneficial to the speed and completeness of expulsion of the contents of the vial (110), i.e., the dissolved or diluted formulation (110b), through the outlet port (130) and into the receiving device (200).

[0063] As further noted above, the drug mixing system (10) according to the first aspect of the present invention, and more particularly the adapter (100) thereof, comprises a piston locking means (126) adapted to lock the position of the piston (125) once a predetermined amount of liquid has been transferred from the reservoir (120) into the vial (110) by forcing the piston (125) into the housing (124). As can be seen, this locking of the piston (125) is achieved by physical interaction of the piston head (125a) with the piston locking means (100) of the adapter. In other words, the piston (125) is locked via its head end (125a). In one embodiment, as shown, for example, in Figures 1A-1E, 4A-4D, 9A-9D, or 10A-10D, the piston locking means (126) is provided in the form of an engagement hook (126a) or multiple engagement hooks (126a, 126a', 126a", etc.), a ratchet mechanism or similar snap-fit ​​locking mechanism (126c), or multiple ratchet mechanisms or similar snap-fit ​​locking mechanisms (126c, 126c', 126c", etc.). The adapter's piston locking means (126) physically interacts with the piston (125), more specifically the piston head (125a), for example, with an engagement hook (126a) that traps the piston and locks it in place by hooking onto the top surface of the piston head (where a user places their fingers when pressing the piston down into the reservoir housing (124)), thereby preventing the piston from retracting from the housing under overpressure forces when the user removes their fingers from the piston head.

[0064] To facilitate insertion of the piston into the housing (124) but prevent rearward movement of the piston (125) after it has been inserted past the position of the engagement hook (126a), the engagement hook (126a) is preferably adapted to have a downward slope only in the direction of piston insertion but a flat, non-sloped surface in the opposite direction (see, for example, FIG. 9D).

[0065] Alternatively, instead of hooking onto the upper surface of the piston head, a resilient, springy tail hook (126b) can be provided below the upper surface of the piston head (as exemplarily shown in Figures 9A-9D), said tail hook (126b) being fixedly associated with or forming an integral part of the piston head (125a) and adapted to be trapped under the engagement hook (126a) or engagement hooks (126a, 126a', 126a", etc.). As shown in more detail in Figure 9D, when the piston (125) is inserted sufficiently deeply, the piston head's tail hook (126b) will spring into one of the three illustrated engagement hooks (126a, 126a', 126a").

[0066] With regard to this expression, the engagement hook (126a) or plurality of engagement hooks (126a, 126a', 126a", etc.), or the snap-fit ​​locking mechanism (126c) or plurality of snap-fit ​​locking mechanisms (126c, 126c', 126c", etc.), it should be understood that these plurality of engagement hooks or snap-fit ​​locking means are intended to enable gradual insertion and locking of the piston (125) in a number of steps, for example, three steps in Figures 9A-9D (transferring 1 / 3, 2 / 3 or 3 / 3 of the liquid contained in the reservoir into the vial), and two steps in Figures 10A-10D (transferring 1 / 2 or 2 / 2 of the liquid).

[0067] Regardless of whether there are only one or multiple insertion steps for the piston 125, the drug mixing system 10, or more specifically its adapter 100, is configured so that the user is made aware of each insertion step by tactile and / or acoustic feedback, e.g., a small "click" sensation and / or sound. Furthermore, the respective insertion depths of the pistons 125 may also be marked on the outside of the adapter's stabilizing wall 170 by visible markings 173, e.g., in the form of raised markings, as shown in Figures 9A and 9B. Alternatively, these markings 173 may be engraved or printed.

[0068] An advantage of providing multiple engaging hooks (126a, 126a', 126a", etc.) or multiple snap-fit ​​locking means (126c, 126c', 126c", etc.) is that different volumes of liquid 120a can be transferred into vial 110, and thus different corresponding overpressures can be generated accordingly, without requiring modifications to reservoir housing 124, often a standardized container such as a syringe or pharmaceutical cartridge 120b. Thus, a user can inhale a specific pharmaceutical dose stored in vial 110 in a shorter time, e.g., half the time if only half the volume of liquid 120a contained in reservoir 120 is used, as long as the solubility and / or viscosity parameters of the formed pharmaceutical formulation 110b permit it. This allows pharmaceutical mixing system 10 according to the present invention greater flexibility in the preparation of dissolved or diluted pharmaceutical formulation 110b than prior art devices.

[0069] In one embodiment, the engagement hook or hooks (126a, 126a', 126a", etc.) are molded into / in a piston guide groove (127a) formed in or through the adapter's stabilizing wall (170), as shown in, for example, Figures 1, 3, 4, and 6-8. In an alternative embodiment, as shown in Figures 9A-9D, the engagement hook or hooks (126a, 126a', 126a") extend from a piston guide rail (127aa) formed on or protruding from the inner surface of the adapter's stabilizing wall (170). More information regarding the piston guide means (127) is provided further below.

[0070] In one embodiment, the piston locking means (126) is provided as one or more through-holes in the stabilizing wall (170) of the adapter, such as the first and second through-holes (126c, 126c') exemplarily shown in Figures 10A-10D, in the form of a snap-fit ​​locking mechanism (126c) or multiple snap-fit ​​locking mechanisms (126c, 126c', 126c", etc.). The two through-holes are arranged to transfer one half or both halves of the liquid (120a) from the reservoir to the vial, thus generating a corresponding overpressure. In order for the piston (125), more particularly the piston head (125a), to be captured or locked in the position of the through-hole(s), the piston head (125a) is provided with a corresponding piston locking protrusion (126d) of appropriate size and shape to "snap-fit" into the through-hole when the piston (125) reaches that position upon insertion. See, for example, the top part of Figure 10C.

[0071] The dimensions and mechanical strength of the stabilizing wall 170, as well as the shape of the through-hole(s), are adapted so that at any point, when the user removes their finger from the piston head 125a, the generated overpressure is not sufficient to overcome the structural resistance of the through-hole(s), meaning that the piston 125 cannot unintentionally unlock and slide back out of the housing 124. At the same time, they are adapted so that the structural resistance of the first "snap fit" can be overcome by the user simply applying slightly greater pressure to the piston head 125a for a short period of time, for example, to push the piston 125 from the first through-hole 126c to the second through-hole 126c'.

[0072] The snap-fit ​​of the piston locking projection 126d into one or more through-holes 126c, 126c', 126c" of the adapter's stabilizing wall 170 can be recognized via tactile and / or acoustic feedback, such as a small "click" sensation and / or sound. Additionally, the piston locking projection 126d on the piston head 125a can also be a different color from the material of the stabilizing wall 170, as shown in FIG. 10C, to visually indicate that it snaps into one of the two through-holes 126c, 126c'. The provision of two through-holes means that the piston can be inserted and locked in half stages, i.e., to transfer one half or both halves of the liquid 120a contained in the reservoir 120 into the vial 110.

[0073] In addition to the above-mentioned multiple piston locking means (126, 126', 126") intended to allow for stepwise piston insertion, the adapter (100) of the drug mixing system (10) according to the first aspect of the present invention may also comprise multiple sets of piston locking means (126), such as, for example, two sets of piston locking means, one set on either side of the adapter (100) and piston head (125a) (i.e., 180° apart), as seen in Figures 1D, 3A, 7A or 9D. This feature provides additional structural stability and allows the piston (125) to be securely locked in place even in the event of high overpressures being generated.

[0074] To facilitate stable piston insertion even when a high overpressure occurs, there may be multiple sets, e.g., two sets, of piston guiding means (127 / 127a / 127b) in addition to multiple sets, e.g., two sets, of piston locking means (126, 126a, 126a', 126a", 126b), as can be seen, for example, in Figures 1D, 3A, 7A, or 9D.

[0075] In addition to the piston locking means (126), the drug mixing system (10) according to the first aspect of the present invention may further comprise piston securing means (129) for preventing loss, cutting or removal of the piston (125) from the reservoir housing (124). See also, for example, Figures 1A-1E, 4A-4D or 9A-9D. As can be further seen from these figures, the piston securing means (129) may also be provided in multiple sets of piston securing means (129), for example, two sets.

[0076] Furthermore, the adapter (100) of the drug mixing system (10) according to the first aspect of the present invention may further comprise a stabilizing wall (170) externally surrounding or encasing at least a portion of the reservoir housing (124), said stabilizing wall (170) being dimensionally stable to support and stabilize the reservoir (120) within the adapter (100) while forcing the piston (125) into the housing (124) and creating an overpressure. Preferably, the stabilizing wall (170) also surrounds or encases at least a portion of the vial (110) from the outside to provide better stability of the drug mixing system (10), preventing the vial (110) and / or reservoir (120) from unintentionally detaching from their respective mounting openings (111, 121), for example, when a user presses down on the piston (125) with the thumb of one hand (300) while firmly gripping the drug mixing system (10) with the same hand (300), as shown in FIG. 8C, for example. In this regard, the expression that the stabilizing wall (170) externally surrounds or encases "at least a portion" of the reservoir housing (124) and optionally the vial (110) should be understood to mean that at least the stabilizing portion of the outer surface of the reservoir housing (124) and optionally the vial (110) is protected from falling off by the stabilizing wall (170), e.g., that portion thereof where, during use, the fingers of the hand (300) holding the drug mixing system (10) and depressing the piston (125) typically generate pressure against the reservoir housing (124) and optionally the vial (110) is covered.

[0077] In one embodiment, the stabilizing wall (170) further surrounds or encases from the outside, in a sleeve-like manner, at least a portion of the adapter (100), in particular at least the first sub-unit (101) thereof. In other words, the stabilizing wall (170) portion is provided separately from the adapter (100), but is firmly connected to the adapter (100). This is beneficial insofar as the stabilizing wall (170) helps to guide the movement of the first and second adapter sub-units (101, 102) towards each other during the activation step of the adapter (100), for example, when inserting the piston (125) into the reservoir housing (124), where the user's hand (300) applies force to the drug mixing system (10), as shown in FIG. 8C , thereby reducing the risk of the two adapter sub-units (101, 102) becoming disengaged from each other.

[0078] In an alternative embodiment, the stabilizing wall (170) is formed as an integral part of the first adapter subunit (101).

[0079] Preferably, at least a portion of the stabilizing wall (170) is provided as a sight glass (171), e.g., by forming the stabilizing wall (170) from a see-through wall material and / or by providing a notch in the wall material, as shown in FIG. 6A. Providing the sight glass (171) is preferred insofar as it allows a user to determine whether the mixture of the formulation (110a) stored in the vial (110) and the liquid transferred from the reservoir (120) to the vial (110) has been dissolved or diluted to a desired degree before activating the liquid discharging means (155, 255), or whether it is necessary to allow additional time and / or vibration of the drug mixing system (10) for sufficient dissolution or dilution. In this regard, it should be understood that the expression "desired degree of dissolution or dilution" typically refers to a homogeneous solution, or, in some cases, a homogeneous suspension or a homogeneous emulsion, with homogeneity being assessed by the naked human eye. Ultimately, however, the "desired degree" is defined by the provider of the pharmaceutical product (i.e., the formulation 110a stored inside the vial 110) and can be found in the product leaflet or similar usage information. Thus, although a homogeneous solution can, in a theoretical example, be obtained from a homogeneous suspension over an extended dissolution time, even if the leaflet or usage information calls for the application of a suspension, a homogeneous suspension should be considered the desired degree of mixing.

[0080] In one embodiment, the piston locking means (126) is formed as an integral part of the stabilizing wall (170), as shown, for example, in Figures 1A-1E, 4A-4D, or 9A-9AD. This is beneficial insofar as it facilitates the casting or injection molding process (i.e., the piston locking means can be cast together with the stabilizing wall) and provides a simple yet dimensionally stable option for locking the piston (125) in place once a predetermined amount of liquid has been transferred from the reservoir (120) to the vial (110). In certain embodiments, both the piston locking means (126) and the optional piston securing means (129) are formed as an integral part of the stabilizing wall (170). See also, for example, Figures 1A-1E, 4A-4D, or 9A-9D.

[0081] In one preferred embodiment, adapter 100 further comprises piston guide means 127 for allowing controlled and stable movement of piston 125 within housing 124 while forcing piston 125 into housing 124 and creating overpressure. For example, as shown in Figures 3A and 3B or 9A and 9B, respectively, piston guide means 127 may take the form of, for example, (i) a piston guide groove 127a and a corresponding protrusion 127b on piston 125, more specifically piston head 125a, that slides through groove 127a while forcing piston 125 into housing 124 and creating overpressure, or (ii) a piston guide groove 127b protruding from the inner surface of stabilizing wall 170. The piston guide groove 127aa may be provided in the form of a guide rail 127aa and a corresponding notch 127bb on the piston or its piston head 125a, for example, an I-beam-shaped guide rail and a corresponding "double-T" notch that slides down the piston guide rail 127aa while forcing the piston 125 into the housing 124 and creating overpressure. Depending on the characteristics of the stabilizing wall 170, such as its thickness and / or hardness, the piston guide groove 127a may be provided on either of the inner surfaces of the stabilizing wall 170 (i.e., the surface facing the reservoir). Alternatively, the piston guide groove 127a may extend entirely through the stabilizing wall 170 in the form of a notch (e.g., as shown in Figures 1, 3, 4, 6, and 7). To further support and stabilize the movement of the piston, the corresponding piston protrusion (127b) sliding through said guide groove (127a) may be provided with a flange (127b', 127b"; see e.g. Figures 7A-7C) contacting the inner surface, or optionally both the inner and outer surfaces, of the stabilizing wall (170). If a piston guide rail (127aa) type piston guide means (127) is selected, this may optionally be provided as an integral part of the stabilizing wall (170), for example by being cast or injection molded together with said wall.

[0082] As mentioned above, the adapter 100 of the drug mixing system 10 may include multiple sets of piston guide means 127 / 127a / 127b, such as two sets of piston guide means, one set on either side of the adapter 100 and piston head 125a (i.e., 180° apart), as seen in Figures 1D, 3A, 7A, or 9D, which provides increased structural stability and facilitates stable piston insertion with reduced rotational slippage, even under high overpressure conditions.

[0083] Since the drug mixing system (10) according to the first aspect of the present invention is intended to be operable with one hand (i.e., holding the system in one hand (300) and depressing the piston (125) using the thumb of said hand (300), in one preferred embodiment the vial attachment opening (111) is provided with a vial fastening means (114) for permanently connecting the vial (110) to the vial attachment opening (111). Similarly, in another preferred embodiment the reservoir attachment opening (121) is provided with a reservoir fastening means (128) for permanently connecting the reservoir (120) to the reservoir attachment opening (121). In one embodiment, both the vial attachment opening and the reservoir attachment opening (111, 121) are equipped with respective vial fastening means and reservoir fastening means (114, 128) for permanently connecting the vial (110) and the reservoir (120) to the respective attachment openings. This is not only beneficial to the handling stability of the drug mixing system 10 during use, but in the more common case of a pre-filled, packaged drug mixing system 10 in which the vial 110 and reservoir 120 are pre-assembled within the adapter 100, it can also serve as a means to prevent misuse, unintended multiple use, or accidental mis-pairing of the formulation 110a with the wrong reservoir of liquid for dissolution, for example.

[0084] As described above, the drug mixing system 10 according to the first aspect of the present invention comprises a reservoir 120 having a housing 124 and a piston 125 sealingly movable within said housing 124. In one embodiment, the reservoir 120 is provided in the form of a syringe 120c, optionally provided with an unthreaded LUER slip (LUER slip) or a threaded LUER lock (LUER lock). Preferably, the syringe 120c or at least its housing 124 is a standard syringe (housing) available on the market, and does not require the provision of a customized opening, for example, suitable for use in the drug mixing system 10 of the present invention. In an alternative embodiment, the reservoir 120 is a drug cartridge 120b. These cartridges 120b are also available on the market in standardized volumes, e.g., 1.5 mL, 3.0 mL, or 5.0 mL. Overall, they are similar to standard syringes, with some differences being that (i) the medication cartridges (120b) are typically made of glass rather than plastic like syringes, and (ii) unlike most syringes, cartridges are typically sealed at their dispensing tip, or "downstream," end, e.g., by a crimped stopper intended to be punctured during use. The opposite, wider, or "upstream" end, of both the syringe and cartridge, is typically sealed by parts of the piston (125), at least for prefilled systems, and typically at least the sealing gasket or stopper (125b) of the piston (125) or plunger is inserted into the housing (124).

[0085] Typically, the vials 110 of the drug mixing system 10 according to the first aspect of the present invention are sealed with pierceable vial closures 112, and the adapter 100 includes respective vial puncture cannulas 113 adapted to pierce the vial closures 112 and access the drug product 110a in the vials 110 during use of the drug mixing system 10. One of the most common types of pierceable closures available commercially, particularly for prefilled vials, is a stopper made of rubber or a similarly sealing elastomeric material as described above, crimped around the neck of the vial 110 with a metal closure, or alternatively secured by heat staking. This provides the best protection for the drug product 110a in the vials 110 from, for example, humidity, oxygen, etc. With regard to the vial puncture cannula (113), it should be understood that this cannula (113) is not identical or the same as the liquid discharge means (155, 255), such as the septum puncture means (230), or more specifically, the septum puncture means in the form of a cannula / hollow needle / spike (230a). The vial puncture cannula (113) is only adapted to puncture the vial lid (112) and (i) allow liquid from the reservoir (120) to enter the vial (110) and (ii) allow the mixture formed from said liquid and formulation (110a) to exit the vial (110) and flow into the internal adapter channel (140) under the increasing overpressure generated within the vial (100).

[0086] In one preferred embodiment, the vial puncture cannula (113) is aligned vertically, rather than at an angle, between the vial (110) and the exit port (130) and its peripheral wall (132) (i.e., their respective central longitudinal axes are aligned, as exemplarily shown in FIG. 1E, or their central longitudinal axes are at least parallel to each other and offset from each other by a short distance of 5 mm or less, preferably 2 mm or less), allowing for unimpeded, overpressure-driven, gravity-assisted, and non-tortuous flow from the vial (110) to the exit port (130). For similar reasons, it is even more preferred that the vial puncture cannula (113) be straight, non-foldable, and non-tortuous. Even more preferably, the vial puncture cannula (113) is 20 mm or less, or 15 mm or less, or 10 mm or less. In one embodiment, the vial puncture cannula (113) exhibits a length of 5 to 20 mm, 5 to 15 mm, or 5 to 10 mm.

[0087] More preferably, the distance between the vial (110) and the outlet port (130), measured between the upstream end of the vial attachment opening (111) (i.e., the surface or plane on which the vial (110) rests) and the downstream end of the outlet port (130) or its peripheral wall (132) (i.e., where the dissolved or diluted formulation (110b) exits the adapter), is 40 mm or less, or 35 mm or less, or 30 mm or less. In one embodiment, the distance between the vial (110) and the outlet port (130) is within the range of 25-40 mm, 25-35 mm, or 25-30 mm. In one embodiment, the distance between the vial (110) and the outlet port (130) is 20 mm or less longer than the length of the vial piercing cannula (113), or 15 mm or less, or 10 mm or less.

[0088] This is advantageous insofar as both a tortuous or winding flow path between the vial 110 and the outlet port 130 and a longer flow path, such as the use of a curved or bent flexible tube in the adapter 100, would be detrimental to expelling the dissolved or diluted formulation 110b from the adapter or using overpressure to transfer the dissolved or diluted formulation 110b to the receiving device 200. This applies in particular when (i) the diluted formulation 110b is not a solution but may instead be an emulsion or suspension, and / or (ii) the amount of liquid 120a transferred from the reservoir 120 to the vial 110, and the resulting overpressure in the vial 110, is dosable (e.g., dosable in half steps or one-third) and does not always use "full force" to expel the adapter 100. When curved or bent tubing, optionally flexible tubing, is used, for example, when the exit port is at a 90° angle to the vial, suspended particles in the diluted formulation 110b are at a high risk of settling at the bend / bend when the overpressure is low, or may be pressed together and solidified at the bend / bend when the overpressure is high. This can lead to drug loss, inaccurate dosing, and clogging and complete unusability of the mixing adapter. The drug mixing system 10 of the present invention helps prevent these drug losses and inaccurate dosing.

[0089] In one embodiment, the reservoirs 120 are also sealed with reservoir lids 122 adapted to open during use of the drug mixing system 10 to access the liquid within the reservoirs 120. This can be either a pierceable lid or another type of closure that opens when the piston 125 is depressed into the housing 124 to release the liquid from the reservoirs 120. For example, it can be a slit or duckbill valve, or a membrane with one or more slits that open under pressure. In certain embodiments, much like the vial 110, the reservoirs 120 are sealed with pierceable reservoir lids 122, and the adapter 100 further includes respective reservoir puncture cannulas 123 adapted to puncture or pierce the reservoir lids 122 and access the liquid within the reservoirs 120 during use of the drug mixing system 10. For example, as mentioned above, reservoir (120) may be a medication cartridge (120b) with a stopper, typically made of rubber or similarly sealing elastomeric material, crimped or otherwise securely fastened to its dispensing tip or "downstream" end and intended to be punctured during use.

[0090] In one embodiment, the adapter (100) comprises a first adapter subunit (101) and a second adapter subunit (102), the first and second adapter subunits (101, 102) being connected to one another and engageable such that the adapter (100) has a rest position and an actuated position. The rest position is a position in which the vial puncture cannula (113) has not yet punctured the vial lid (112), or, as the case may be, the vial and reservoir puncture cannula (113, 123) has not yet punctured the respective vial and reservoir lids (112, 122). The activated position is the position where, during use of the drug mixing system 10, the first and second adapter subunits (101, 102) are shifted toward each other such that the vial cannula (113) pierces the vial lid (112) and thereby accesses the formulation (110a) in the vial (110), or, as the case may be, the vial and reservoir piercing cannulae (113, 123) pierce the respective vial and reservoir lids (112, 122) and thereby access the formulation (110a) in the vial (110) and the liquid in the reservoir (120). The provision of the two subunits (101, 102) of the adapter (110), and thus the two positions, "rest" versus "actuated," is beneficial insofar as the vial contents, and optionally both the vial contents and the reservoir contents, are protected from, e.g., humidity, oxygen, etc., when the drug mixing system (10) is not yet in use. In other words, in one embodiment, prior to use (e.g., for shipping, delivery, and storage), the adapter (100) is provided in its rest position.

[0091] In one embodiment, the drug mixing system 10) or its adapter 100 includes an indicator window 172 that typically visually indicates to a user whether the adapter 100 is in its activated position (i.e., whether the two adapter subunits are moving toward each other and thus the vial 110 and reservoir 120 are opened / punctured), as shown, for example, in FIGS. 9A-9C or 10B. The indicator window 172 may, for example, turn green when the adapter 100 is activated. Alternatively, or in addition, the drug mixing system 10) or its adapter 100 may include a tactile activation indicator instead of a color-changing indicator, such as a knob that pops out through the indicator window 172 when the adapter 100 is brought into its activated position.

[0092] Typically, the adapter 100 is provided to the user in a pre-assembled form, e.g., with the first and second adapter subunits 101, 102 of the adapter 100 pre-assembled. In one preferred embodiment, the first and second adapter subunits 101, 102 are permanently connected when in the rest position. This prevents the two subunits from unintentionally separating prior to use when opening the drug mixing system 10 and / or moving the adapter 100 from the rest position to the actuated position. In a further preferred embodiment, the first and second adapter subunits 101, 102 are permanently connected when in the actuated position. This prevents the two subunits from unintentionally separating during use (e.g., when pushing the piston 125 into the reservoir housing 124), thereby preventing leakage or contamination of the contents of the vial and / or reservoir.

[0093] To enable these non-removable connections between the first and second adapter subunits (101, 102), in one embodiment, the first and / or second adapter subunits (101, 102) comprise at least one adapter subunit locking means (103) for locking engagement between the first adapter subunit (101) and the second adapter subunit (102). In a particular embodiment, the adapter subunit locking means (103) is adapted to non-removably lock the adapter (100) in a rest position or in an actuated position. In a more particular embodiment, the adapter subunit locking means (103) is provided in the form of one or more subunit locking hooks (103a) and corresponding subunit locking grooves (103b) located inside the first and second adapter subunits (101, 102). In a further particular embodiment, the first and / or second adapter subunit (101, 102) comprises at least two adapter subunit locking means (103) for engagement of the first adapter subunit (101) with the second adapter subunit (102). In yet a further particular embodiment, one of the at least two adapter subunit locking means (103) is engaged in a rest position and the other is engaged in an actuated position.

[0094] To move the adapter (100) from its rest position to its actuated position, the two adapter subunits (101, 102) are typically shifted toward each other or pressed or "clicked" together, for example, by placing one hand on one side of the drug mixing system (10), with the thumb(s) placed on the flat bottom or lower end of the adapter (100) and the fingers pressing into either the bottom (115) of the vial (110) or, preferably, into one or more dedicated areas shaped as patterned ledge(s) (105') for finger placement, and holding the drug mixing system (10), for example, in one hand (300) as shown in FIG. 8A or 10B (or between two hands (300) as shown in FIG. 8B), with said ledge(s) overhanging, for example, from the stabilizing wall (170). Pressing not against the bottom (115) of the vial (110) but instead against a dedicated area formed as a patterned shelf (105') for placing a finger is preferable insofar as it puts less strain on the vial fixation and avoids the vial (110) falling out.

[0095] In one embodiment, the first and second adapter subunits (101, 102) are adapted to be shifted toward each other with one hand. Thus, in one preferred embodiment, the adapter (100), preferably the second adapter subunit (102), includes at least one dedicated portion for resting one or more fingers (105, 105′) when shifting the adapter (100) from the rest position to the working position. This limits the risk of the finger(s) slipping, making it easier to hold and use the adapter (100) with one hand. The dedicated portion (105, 105′) may be, for example, a recess approximately the size of a fingertip, or a wing-shaped or curved indentation located at the bottom end of the second adapter subunit (102), allowing one or two fingers to rest comfortably in the recess. Alternatively, as shown in Figures 7A-7C or 8A-8C, the lower end of the second adapter subunit (102) can be provided as a simple flat surface upon which, for example, the opposable thumbs can rest, and dedicated site(s) can be provided in the form of patterned ledges (105') extending at an angle of approximately 90° on at least one side, preferably both sides, of the drug mixing system (10; e.g., extending from the stabilizing wall (170)) for resting one or more fingers during use, particularly while moving the adapter (100) from its rest position to its actuated position. Alternatively, relative to the finger placement shown in Figure 8A, the user can position the drug mixing system (10) between their spread index and middle fingers during the adapter (100) activation step.

[0096] In one embodiment, the first adapter subunit (101) includes at least a vial mounting opening (111) adapted to hold a vial (110), a reservoir mounting opening (121) adapted to hold a reservoir (120), and, optionally, a stabilizing wall (170) externally surrounding or encasing at least portions of the reservoir housing (124). Or, in other words, the vial mounting opening (111), reservoir mounting opening (121), and, optionally, the stabilizing wall (170) of the adapter (100) are part(s) of the adapter first subunit (101). If the stabilizing wall (170) is present, it can be formed as an integral part of the first adapter subunit (101), as described above.

[0097] In one embodiment, the second adapter subunit 102 includes at least the switch valve 150 and the outlet port 130. In other words, the switch valve 150 and the outlet port 130 of the adapter 100 are part(s) of the second subunit 102 of the adapter.

[0098] As described above, to move the adapter (100) from its rest position to its actuated position, the two adapter subunits (101, 102) are typically shifted toward one another. To facilitate this movement, in one embodiment, the adapter (100) includes adapter subunit guide means that guide the movement of the first adapter subunit (101) and the second adapter subunit (102) as they are shifted toward one another from the rest position to the actuated position. Similar to the piston guide means (127), the adapter subunit guide means, in one embodiment, is provided in the form of at least one subunit guide recess in the first adapter subunit (101) and at least one corresponding subunit guide protrusion that fits into a recess in the second adapter subunit (102), or vice versa. In embodiments in which the stabilizing wall (170) externally surrounds or encases at least a portion of the first and second adapter subunits (101, 102) in a sleeve-like manner, for example as shown in Figures 1A-1E or 4A-4D, the stabilizing wall (170) may also function as an adapter subunit guide means, insofar as it guides the movement of the two subunits towards each other.

[0099] In one embodiment, the vial 110 of the pharmaceutical mixing system 10 according to the first aspect of the present invention exhibits a central longitudinal axis "A" (exemplary as shown in FIG. 1E or FIG. 6B), said central longitudinal axis "A" being positioned vertically or essentially vertically during use, more specifically during the evacuation or transfer of the dissolved or diluted pharmaceutical formulation 110b from the vial 110 through the outlet port 130. This is advantageous insofar as it helps ensure complete and rapid evacuation of the vial 110. Accordingly, in one preferred embodiment, the pharmaceutical mixing system 10 and the receiving device 200 are adapted such that their connection ensures this vertical or essentially vertical position of the vial 110 or its said central longitudinal axis "A" during use. For example, in one embodiment, as shown in FIG. 6B , the vial (110) exhibits a central longitudinal axis “A,” the receiving device (200) exhibits a central longitudinal axis “C,” and the central longitudinal axis “A” of the vial is oriented perpendicular to the central longitudinal axis “C” of the receiving device when the drug mixing system (10) is connected to the receiving device (200). The receiving device (200), e.g., a nebulizer (201), e.g., a vibrating mesh nebulizer (202), can be placed, for example, with its flat backside on a table with its inlet opening (210) facing upward or toward the user. The drug mixing system (10) can then be placed on top and connected to the receiving device (200) via the connecting and connected means (160, 260) such that the central longitudinal axis “A” of the vial is oriented vertically or essentially vertically.

[0100] In one embodiment, the vial (110) exhibits a central longitudinal axis "A" and the reservoir (120) exhibits a central longitudinal axis "B" (see, e.g., FIG. 6B), and the vial and reservoir mounting openings (111, 121) are arranged to hold the vial (110) and reservoir (120) in a position where the central longitudinal axes "A" and "B" are disposed at an angle of less than 75°, preferably less than 60°, more preferably less than 50°, or even less than 20°, e.g., 0°. In certain embodiments, the central longitudinal axes "A" and "B" are disposed between 20° and 0°, preferably between 10° and 0°, more preferably between 5° and 0°, e.g., 0°. For example, as exemplarily shown in FIG. 1E or FIG. 6B, the two central longitudinal axes "A" and "B" can be disposed at an angle of approximately 0°, in other words, parallel to one another. In alternative embodiments, the central longitudinal axes "A" and "B" are disposed at an angle between 70° and 20°, or between 60° and 30°, or between 50° and 40°, for example, 45°.

[0101] In one embodiment, the vial and reservoir mounting openings (111, 121) of the adapter (100) are arranged such that at least the central longitudinal axis "A" of the vial, and optionally both the central longitudinal axes "A" and "B" of the vial and reservoir, are aligned vertically or essentially vertically during use, or more specifically during the expulsion or transfer of dissolved or diluted formulation (110b) from the vial (110) through the outlet port (130).

[0102] In one embodiment, the adapter 100, and optionally the drug mixing system 10, as a whole, is sterilizable. In certain embodiments, the adapter 100, and optionally the drug mixing system 10, as a whole, is sterilizable in its packaged state. In certain embodiments, the adapter 100, and optionally the drug mixing system 10, as a whole, is sterilizable with ethylene oxide and / or gamma irradiation. In a preferred embodiment, the adapter 100, and optionally the drug mixing system 10, as a whole, is stored and delivered in a pre-packaged, sterile state (see, e.g., package 400 in FIG. 10A). It is further preferred that the vial 110 and reservoir 120 be pre-assembled within the vial attachment opening 111 and reservoir attachment opening 121, respectively, of the adapter 100 of the drug mixing system 10.

[0103] In one embodiment, the drug mixing system (10) is a valve-type drug mixing system (10b) (i.e., a liquid retaining means (145) in the form of a switch valve (150)), and the adapter (100), and optionally the entire drug mixing system (10), are stored and delivered in a pre-packaged state with the switch valve (150) of the adapter (100) in valve position 1.

[0104] In one embodiment, the formulation (110a) in the vial (110) is provided in powder form, such as a powder for reconstitution, or as a liquid. For example, in certain embodiments, the formulation (110a) in the vial (110) is provided in lyophilized form, i.e., a lyophilized powder. In alternative embodiments, the formulation (110a) in the vial (110) is provided as a liquid, such as a drug concentrate and / or liquid solubilizer. In one embodiment, the formulation (110a) in the vial (110) includes at least one drug, optionally a combination of drugs.

[0105] In one embodiment, liquid 120a in reservoir 120 is a pharmaceutically acceptable liquid. For example, in certain embodiments, the pharmaceutically acceptable liquid is an injectable liquid, such as water for injection (aqueous injection), and / or an inhalable liquid.

[0106] In one embodiment, the drug mixing system (10) is intended to be disposable.

[0107] In a second aspect, the present invention relates to an adapter (100) for a drug mixing system (10) according to the first aspect of the invention. Accordingly, any embodiment, or particular or preferred embodiment, disclosed herein in relation to the drug mixing system (10) according to the first aspect of the invention may be applied to the adapter (100) according to this second aspect of the invention. For example, in one embodiment, the adapter (100) comprises a piston locking means (126) adapted to lock the position of the piston (125) when a predetermined amount of liquid is transferred from the reservoir (120) into the vial (110) by forcing the piston (125) into the housing (124), thereby creating and storing an overpressure. Alternatively, in one embodiment, the adapter (100) comprises a stabilizing wall (170) that externally surrounds or encases at least a portion of the reservoir housing (124), said stabilizing wall (170) being dimensionally stable to support and stabilize the reservoir (120) within the adapter (100) while forcing the piston (125) into the housing (124) and generating an overpressure.

[0108] In a third aspect, the present invention relates to a method for preparing a dissolved or diluted formulation (110b), optionally a pharmaceutical solution, from a formulation (110a) stored in a vial (110) using a pharmaceutical mixing system (10) according to the first aspect of the invention. Accordingly, any embodiment disclosed herein in relation to the pharmaceutical mixing system (10) according to the first aspect of the invention, or specific or preferred embodiments thereof, may be applied to the preparation method according to this third aspect of the invention, including any of the operational steps described above for the pharmaceutical mixing system (10) according to the first aspect of the invention or its adapter (100) according to the second aspect of the invention.

[0109] More specifically, according to a third aspect, the present invention provides a method for producing a medicament for the treatment of a medicament comprising the steps of: a) providing a pharmaceutical mixing system (10) according to a first aspect of the present invention; b) transferring a predetermined amount of liquid from the reservoir (120) into the vial (110) by pushing the piston (125) into the housing (124) while the liquid retaining means (145) blocks the flow of at least the dissolved or diluted formulation (110b) through the outlet port (130), thereby creating an overpressure and a mixture of the formulation (110a) and the liquid; c) once a predetermined amount of liquid has been transferred from the reservoir (120) to the vial (110), locking the piston (125) in place with the piston locking means (126), thereby storing the overpressure created in step b; d) dissolving or diluting the mixture of formulation (110a) and liquid resulting from steps b) and c) to the desired extent, optionally assisting this dissolving or diluting process by agitating the drug mixing system (10); e) using the stored overpressure generated in steps b) and c) to expel or transfer the dissolved or diluted formulation (110b) from the vial (110) through the outlet port (130) by actuating the liquid expelling means (155, 255), thereby forcing the piston (125) into the housing (124) and locking the piston (125) in place.

[0110] For example, in one embodiment, the method comprises the following subsequent steps: a) providing a valve-type drug mixing system (10b) according to a first aspect of the present invention, wherein the liquid retaining means (145) is provided in the form of a switch valve (150), the internal adapter channel (140) and the switch valve (150) being adapted to at least allow selective fluid connection between the vial (110) and the reservoir (120) while blocking fluid connection to the outlet port (130) when in valve position 1, and to allow selective fluid connection between the vial (110) and the outlet port (130) while blocking fluid connection to the reservoir (120) when in valve position 2; b) with the switch valve (150) in or placed in valve position 1, transferring a predetermined amount of liquid from the reservoir (120) into the vial (110) by forcing the piston (125) into the housing (124), thereby creating an overpressure and a mixture of the formulation (110a) and the liquid; c) once a predetermined amount of liquid has been transferred from the reservoir (120) to the vial (110), locking the piston (125) in place with the piston locking means (126), thereby storing the overpressure created in step b; d) dissolving or diluting the mixture of formulation (110a) and liquid resulting from steps b) and c) to the desired extent, optionally assisting this dissolving or diluting process by agitating the drug mixing system (10); e) using the stored overpressure generated in steps b) and c) by placing the switch valve (150) in valve position 2, thereby forcing the piston (125) into the housing (124) and locking the piston (125) in place, to expel or transfer the dissolved or diluted formulation (110b) from the vial (110) through the outlet port (130).

[0111] In an alternative embodiment, the method comprises the following subsequent steps: a) providing a sealed-type drug mixing system (10a) according to a first aspect of the present invention, wherein a liquid retaining means (145) is provided in the form of a septum (131) covering an outlet port (130), and a liquid discharging means (155, 255) is provided in the form of a septum piercing means (230); b) transferring a predetermined amount of liquid from the reservoir (120) into the vial (110) by pushing the piston (125) into the housing (124) while the septum (131) blocks the flow of at least the dissolved or diluted formulation (110b) through the outlet port (130), thereby creating an overpressure and a mixture of the formulation (110a) and the liquid; c) once a predetermined amount of liquid has been transferred from the reservoir (120) to the vial (110), locking the piston (125) in place with the piston locking means (126), thereby storing the overpressure created in step b; d) dissolving or diluting the mixture of formulation (110a) and liquid resulting from steps b) and c) to the desired extent, optionally assisting this dissolving or diluting process by agitating the drug mixing system (10); e) actuating the liquid discharging means (155, 255) by puncturing the septum (131) with the septum puncturing means (230), thereby forcing the piston (125) into the housing (124) and locking the piston (125) in place, thereby discharging or transferring the dissolved or diluted formulation (110b) from the vial (110) through the outlet port (130) using the stored overpressure generated in steps b) and c).

[0112] In one embodiment of the method according to the third aspect of the present invention, a drug mixing system (10) including the first and second adapter subunits (101, 102) described above is provided in step a), and the drug mixing system (10) is activated by moving the adapter (100) from the rest position to the activated position as described above. In a specific embodiment, the adapter (100) is moved from the rest position to the activated position by shifting the first and second adapter subunits (101, 102) of the adapter (100) toward each other. In a more specific embodiment, the first and second adapter subunits (101, 102) of the adapter (100) are shifted, or at least can be shifted, toward each other using one hand.

[0113] In one embodiment of the method according to the third aspect of the present invention, the dissolved or diluted formulation (110b) is transferred from the vial (110) via the outlet port (130) to a receiving device (200) for receiving the dissolved or diluted formulation (110b) from the vial (110).

[0114] Preferably, to make use of the drug mixing system 10 as simple and convenient as possible for the user, the drug mixing system 10 is provided to the user with all components combined together (e.g., in the same primary packaging 400): the adapter 100, the vial 110 containing the formulation 110a, and the reservoir 120 for containing the liquid 120a for dissolving or diluting the formulation 110a), and more preferably, the vial 110 and the reservoir 120 pre-assembled in their respective mounting openings 111, 121. However, in embodiments in which the adapter (100) is provided separately from the vial (110) containing the formulation (110a) and / or the reservoir (120) for containing a liquid for dissolving or diluting the formulation (110a), the vial (110) and / or the reservoir (120) are then coupled to the respective vial and reservoir mounting openings (111, 121) of the adapter (100) to provide the drug mixing system (10) of method step a).

[0115] Additionally, the drug mixing and injection system of the present invention conserves materials by using fewer vials which reduces the consumption of disposable materials. Item List

[0116] 1. A pharmaceutical mixing system (10) for dissolving or diluting a pharmaceutical preparation (110a) stored in a vial (110) prior to use, the pharmaceutical mixing system (10) comprising: an adapter (100) adapted to hold the vial (110) containing the pharmaceutical preparation (110a); and a reservoir (120) for containing a liquid (120a) for dissolving or diluting the pharmaceutical preparation (110a), the reservoir (120) comprising a housing (124) and a piston (125) sealingly movable within the housing; The adapter (100) a vial mounting opening (111) adapted to hold a vial (110); a reservoir mounting opening (121) adapted to hold a reservoir (120); an outlet port (130); an internal adapter channel (140) fluidly connecting the vial mounting opening (111) and the reservoir mounting opening (121) with the outlet port (130); a liquid retaining means (145) adapted to block the flow of at least the dissolved or diluted formulation (110b) through the outlet port (130); the adapter (100) comprising a piston locking means (126) adapted to lock the position of the piston (125) when a predetermined amount of liquid is transferred from the reservoir (120) into the vial (110) by forcing the piston (125) into the housing (124), thereby creating and storing an overpressure; The drug mixing system (10) is adapted to expel or transfer the dissolved or diluted formulation (110b) from the vial (110) through the outlet port (130) when the liquid discharge means (155, 255) is actuated using an overpressure generated by forcing the piston (125) into the housing (124).

[0117] 2.a) For a sealed type drug mixing system (10a), a liquid retaining means (145) is provided in the form of a septum (131) covering the outlet port (130); A liquid discharge means (155, 255) is provided in the form of a septum piercing means (230) whereby, upon actuation, the septum (131) is pierced by the septum piercing means (230) and the dissolved or diluted formulation (110b) is expelled or transferred from the vial (110) through the outlet port (130) using overpressure generated by forcing the piston (125) into the housing (124); b) for a valve-type drug mixing system (10b), the liquid retaining means (145) is provided in the form of a switch valve (150), the internal adapter channel (140) and the switch valve (150) being adapted to at least allow selective fluid communication between the vial (110) and the reservoir (120) while blocking fluid communication to the outlet port (130) when in valve position 1, and to allow selective fluid communication between the vial (110) and the outlet port (130) while blocking fluid communication to the reservoir (120) when in valve position 2; a liquid discharging means (155, 255) is provided in the form of a switch valve operating means (156) adapted to, upon actuation, place the switch valve (150) in valve position 2, whereby, when the switch valve (150) is placed in valve position 2, the dissolved or diluted formulation (110b) is expelled or transferred from the vial (110) through the outlet port (130) using an overpressure created by forcing the piston (125) into the housing (124); Item 1. The pharmaceutical mixing system (10) according to item 1.

[0118] 3. The pharmaceutical mixing system (10) according to item 1 or 2, wherein the dissolved or diluted formulation (110b) is transferred from the vial (110) through the outlet port (130) into a receiving device (200) for receiving the dissolved or diluted formulation (110b) from the vial (110).

[0119] 4. The drug mixing system (10) according to item 3, wherein the receiving device (200) is a nebulizer (201).

[0120] 5. The drug mixing system (10) described in item 3 or 4, wherein the receiving device (200) is a vibrating mesh nebulizer (202) and the dissolved or diluted formulation (110b) from the vial (110) is transferred into or received by the nebulization chamber (202a) of the vibrating mesh nebulizer (202).

[0121] 6. A drug mixing system (10) according to any one of items 1 to 5, wherein the liquid releasing means (155, 255) is provided as part of the receiving device (200) or the adapter (100), optionally as an integral part.

[0122] 7. A drug mixing system (10) according to any one of items 1 to 6, wherein the adapter (100) and the receiving device (200) respectively comprise a connecting means (160) and a connected means (260) for connecting the drug mixing system (10) to the receiving device (200).

[0123] 8. The drug mixing system (10) described in item 7, wherein the connecting means (160) and the connected means (260) are adapted so that when they are connected, the drug mixing system (10) and the receiving device (200) form a leak-proof connection.

[0124] 9. A drug mixing system (10) according to item 7 or 8, wherein the adapter (100) is provided with a male connecting means (160m) that can be inserted into the female connecting means (260f) of the receiving device (200).

[0125] 10. A drug mixing system (10) according to any one of items 7 to 9, wherein the connecting means (160) and the connected means (260) are adapted to activate the liquid discharging means (155, 255) when they are connected.

[0126] 11. The connecting means (160) and the connected means (260) are a method in which the septum piercing means (230) is adapted to automatically pierce the septum (131) when the seal-type drug mixing system (10a) and the receiving device (200) are connected; - The drug mixing system (10) according to item 10, wherein when the valve-type drug mixing system (10b) is connected to the receiving device (200), the switch valve (150) is automatically placed in valve position 2.

[0127] 12. A drug mixing system (10) as described in item 11, adapted in such a way that when the valve-type drug mixing system (10b) is connected to the receiving device (200), the switch valve (150) is automatically placed in valve position 2, and is placed in valve position 2 through physical interaction of the connecting means (160) and / or the connected means (260) with the switch valve operating means (156) of the adapter (100b).

[0128] 13. The drug mixing system (10b) according to item 12, wherein the switch valve operating means (156) is part of the adapter (100b) of the valve-type drug mixing system (10b).

[0129] 14. The drug mixing system (10b) according to item 13, wherein the switch valve operating means (156) is provided in the form of a protrusion (156a), such as a push button, protruding from the male connecting means (160m) of the adapter (100b), the male connecting means (160m) being insertable into the female connecting means (260f) of the receiving device (200), and when the male connecting means (160m) is inserted into the female connecting means (260f), the protruding switch valve operating means (156a) is pushed into the male connecting means (160m), thereby moving the switch valve (150) to valve position 2 and using overpressure, discharging or transferring the dissolved or diluted formulation (110b) from the vial (110) to the receiving device (200) through the outlet port (130).

[0130] 15. The drug mixing system (10b) according to item 14, wherein the protruding switch valve operating means (156a) of the adapter (100b) and / or the female mating means (260f) of the receiving device (200) are provided with an inclined or sloped surface to facilitate controlled and stable movement of the protruding switch valve operating means (156a) when pressed into the male mating means (160m).

[0131] 16. A drug mixing system (10b) according to item 14 or 15, wherein the protruding switch valve operating means (156a) of the adapter (100b) is covered by a protective wall or protective cover, which is adapted and arranged to prevent premature and / or unintentional movement of the protruding switch valve operating means (156a) before connecting the drug mixing system (10) to the receiving device (200).

[0132] 17. The pharmaceutical mixing system (10b) according to item 14 or 16, wherein the receiving device (200) comprises a valve operating pin (256), and when the male connecting means (160m) of the adapter (100b) is inserted into the female connecting means (260f) of the receiving device (200), the protruding switch valve operating means (156a) is pushed into the male connecting means (160m) by the valve operating pin (256), thereby moving the switch valve (150) to valve position 2, and the dissolved or diluted formulation (110b) is expelled or transferred from the vial (110) to the receiving device (200) via the outlet port (130) using overpressure.

[0133] 18. A drug mixing system (10) according to any one of items 3 to 11, wherein the seal type drug mixing system (10a) is provided with a liquid discharge means (155, 255) in the form of a septum puncturing means (230), and the septum puncturing means (230) is provided as part of the receiving device (200), optionally as an integral part.

[0134] 19. A drug mixing system (10) according to item 18, wherein the septum piercing means (230) is arranged in the center of a spoked wheel-shaped portion (220) arranged in the inlet opening (210) of the receiving device through which the dissolved or diluted formulation (110b) is received.

[0135] 20. A drug mixing system (10) according to item 19, wherein the spoke wheel-shaped portion (220) is shaped and / or positioned within the inlet opening (210) of the receiving device (200) so that the puncturing tip (231) of the septum puncturing means (230) does not overhang or protrude from the surface of the outer casing (240) of the receiving device (200).

[0136] 21. A drug mixing system (10) according to any one of items 18 to 20, wherein the septum puncturing means (230) is provided in the form of a septum puncturing cannula (230a), or a hollow needle, or a so-called "spike".

[0137] 22. A drug mixing system (10) according to any one of items 1 to 21, wherein the piston locking means (126) is provided in the form of an engaging hook (126a) or a plurality of engaging hooks (126a, 126a', 126a", etc.), a ratchet mechanism or similar snap-fit ​​locking mechanism (126c), or a plurality of ratchet mechanisms or similar snap-fit ​​locking mechanisms (126c, 126c', 126c", etc.).

[0138] 23. A drug mixing system (10) described in any one of items 1 to 22, wherein the adapter (100) further comprises a stabilizing wall (170) that externally surrounds or encases at least a portion of the reservoir housing (124), the stabilizing wall (170) being dimensionally stable to support and stabilize the reservoir (120) within the adapter (100) while forcing the piston (125) into the housing (124) and generating an overpressure.

[0139] 24. The pharmaceutical mixing system (10) according to item 23, wherein the stabilizing wall (170) also externally surrounds or encases at least a portion of the vial (110).

[0140] 25. A drug mixing system (10) according to item 23 or 24, wherein at least a portion of the stabilizing wall (170) is provided as a viewing window (171), for example by the stabilizing wall (170) being formed from a transparent wall material and / or by providing a notch in the wall material.

[0141] 26. A drug mixing system (10) according to any one of items 1 to 25, wherein the piston locking means (126) is formed as an integral part of the stabilizing wall (170).

[0142] 27. A drug mixing system (10) according to any one of items 1 to 26, wherein the adapter (100) further comprises a piston guide means (127) for forcing the piston (125) into the housing (124) and generating an overpressure while allowing controlled and stable movement of the piston (125) within the housing (124).

[0143] 28. Piston guide means (127) a configuration of a piston guide groove (127a) in the stabilizing wall (170) and a corresponding protrusion (127b) on the piston (125) that slides down the groove (127a) while forcing the piston (125) into the housing (124) and creating overpressure, or 28. The drug mixing system (10) according to item 27, provided in the form of a piston guide rail (127aa) protruding from the inner surface of the stabilizing wall (170) and a corresponding notch (127bb) on the piston (125), for example, in the form of an I-beam shaped guide rail and a corresponding "double T" notch that pushes the piston (125) into the housing (124) and slides down the piston guide rail (127aa) while creating overpressure.

[0144] 29. A drug mixing system (10) according to any one of items 1 to 28, wherein the vial mounting opening (111) is provided with a vial fixing means (114) for non-detachably connecting the vial (110) to the vial mounting opening (111).

[0145] 30. A drug mixing system (10) according to any one of items 1 to 29, wherein the reservoir attachment opening (121) is provided with a reservoir fixing means (128) for non-removably connecting the reservoir (120) to the reservoir attachment opening (121).

[0146] 31. A drug mixing system (10) according to any one of items 2 to 30, wherein the drug mixing system (10) is a valve-type drug mixing system (10b) having a liquid retaining means (145) in the form of a switch valve (150), and the switch valve (150) is a three-way switch valve having three openings for selectively enabling fluid connection between the vial mounting opening (111), the reservoir mounting opening (121), and the outlet port (130).

[0147] 32. A drug mixing system (10) according to any one of items 2 to 31, wherein the drug mixing system (10) is a valve-type drug mixing system (10b) having a liquid retaining means (145) in the form of a switch valve (150), the switch valve (150) being rotatable or shiftable.

[0148] 33. A drug mixing system (10) according to any one of items 2 to 32, wherein the drug mixing system (10) is a valve-type drug mixing system (10b) having a liquid retaining means (145) in the form of a switch valve (150), and the switch valve (150) is adapted to switch to a third position, valve position 3, and cut off the fluid connection between the vial mounting opening (111), the reservoir mounting opening (121) and the outlet port (130).

[0149] 34. A drug mixing system (10) according to any one of items 1 to 33, wherein the reservoir (120) is provided in the form of a syringe (120c), optionally a syringe with an unthreaded LUER slip (LUER slip) or a syringe with a threaded LUER lock (LUER lock), or the reservoir (120) is a drug cartridge (120b).

[0150] 35. A drug mixing system (10) according to any one of items 1 to 34, wherein the vials (110) are sealed with pierceable vial lids (112), and the adapter (100) includes respective vial puncture cannulas (113) adapted to pierce the vial lids (112) and access the formulation (110a) in the vials (110) during use of the drug mixing system (10).

[0151] 36. A drug mixing system (10) as described in item 35, wherein the reservoir (120) is also sealed with a reservoir lid (122) adapted to open during use of the drug mixing system (10) to access the liquid in the reservoir (120).

[0152] 37. A drug mixing system (10) according to item 35 or 36, wherein the reservoirs (120) are sealed with puncturable reservoir lids (122), and the adapter (100) further comprises respective reservoir puncture cannulas (123) adapted to pierce the reservoir lids (122) and access the liquid in the reservoirs (120) during use of the drug mixing system (10).

[0153] 38. An adapter (100) comprises a first adapter subunit (101) and a second adapter subunit (102), the first and second adapter subunits (101, 102) are connected to each other, and the adapter (100) a rest position in which the vial puncture cannula (113) has not yet punctured the vial lid (112), or, as the case may be, the vial and reservoir puncture cannula (113, 123) has not yet punctured the respective vial and reservoir lid (112, 122); During use of the drug mixing system (10), the first and second adapter subunits (101, 102) are shifted toward each other, thereby positioning the vial cannula (113) to pierce the vial closure (112), thereby accessing the drug product (110a) within the vial (110); or, as the case may be, an actuated position in which the vial and reservoir piercing cannulae (113, 123) pierce the caps (112, 122) of the respective vials and reservoirs, thereby accessing the formulation (110a) in the vial (110) and the liquid in the reservoir (120); 38. The drug mixing system (10) according to any one of items 35 to 37, which is engageable to have

[0154] 39. A drug mixing system (10) according to item 38, wherein the adapter (100) is provided to the user in a pre-assembled form, for example the first and second adapter subunits (101, 102) of the adapter (100) being pre-assembled.

[0155] 40. The drug mixing system (10) of item 38 or 39, wherein the adapter (100) is provided in its rest position prior to use (e.g., for shipping, delivery, and storage).

[0156] 41. A drug mixing system (10) according to any one of items 38 to 40, wherein in the rest position the first and second adapter subunits (101, 102) are permanently connected.

[0157] 42. A drug mixing system (10) according to items 38 to 41, wherein in the activated position the first and second adapter subunits (101, 102) are permanently connected.

[0158] 43. A drug mixing system (10) according to any one of items 38 to 42, wherein the first and / or second adapter subunit (101, 102) comprises at least one adapter subunit locking means (103) for locking engagement between the first adapter subunit (101) and the second adapter subunit (102).

[0159] 44. A drug mixing system (10) according to item 43, wherein the adapter subunit locking means (103) is adapted to irremovably lock the adapter (100) in a rest position or in an actuated position.

[0160] 45. A drug mixing system (10) according to item 43 or 44, wherein the adapter subunit locking means (103) is provided in the form of one or more subunit locking hooks (103a) and corresponding subunit locking grooves (103b) arranged inside the first and second adapter subunits (101, 102).

[0161] 46. ​​A drug mixing system (10) according to items 43 to 45, wherein the first and / or second adapter subunit (101, 102) comprises at least two adapter subunit locking means (103) for engagement of the first adapter subunit (101) with the second adapter subunit (102).

[0162] 47. A drug mixing system (10) according to item 45, wherein one of the at least two adapter subunit locking means (103) is engaged in the rest position and the other is engaged in the actuated position.

[0163] 48. A drug mixing system (10) according to items 38 to 47, wherein the first adapter subunit (101) comprises at least a vial mounting opening (111) adapted to hold a vial (110), a reservoir mounting opening (121) adapted to hold a reservoir (120), and optionally a stabilizing wall (170) externally surrounding or encasing at least portions of the reservoir housing (124).

[0164] 49. A drug mixing system (10) according to any one of items 38 to 48, wherein the stabilizing wall (170) is formed as an integral part of the first adapter subunit (101).

[0165] 50. The drug mixing system (10) according to any one of items 38 to 49, wherein the second adapter subunit (102) comprises at least a switch valve (150) and an outlet port (130).

[0166] 51. A drug mixing system (10) according to any one of items 38 to 50, wherein the adapter (100) is provided with adapter subunit guide means (104) for guiding the movement of the first adapter subunit (101) and the second adapter subunit (102) when the first adapter subunit (101) and the second adapter subunit (102) are shifted towards each other from a rest position to an actuated position.

[0167] 52. A drug mixing system (10) according to any one of items 38 to 51, wherein the adapter subunit guide means (104) is provided in the form of at least one subunit guide recess (104a) in the first adapter subunit (101) and at least one corresponding subunit guide protrusion (104b) that fits into the recess (104a) in the second adapter subunit (102), or vice versa.

[0168] 53. A drug mixing system (10) according to any one of items 38 to 52, wherein the first adapter subunit and the second adapter subunit (101, 102) are adapted so that they can be shifted towards each other with one hand.

[0169] 54. A drug mixing system (10) according to any one of items 38 to 53, wherein the adapter (100), preferably the second adapter subunit (102), includes at least one dedicated site for resting one or more fingers (105, 105') when moving the adapter (100) from the rest position to the actuated position.

[0170] 55. A pharmaceutical mixing system (10) according to any one of items 1 to 54, wherein the vial (110) exhibits a central longitudinal axis "A", and wherein the central longitudinal axis "A" is positioned vertically or essentially vertically during use.

[0171] 56. A drug mixing system (10) according to any one of items 5 to 55, wherein the vial (110) exhibits a central longitudinal axis "A", the receiving device (200) exhibits a central longitudinal axis "C", and the central longitudinal axis "A" of the vial is oriented perpendicular to the central longitudinal axis "C" of the receiving device when the drug mixing system (10) is connected to the receiving device (200).

[0172] 57. A pharmaceutical mixing system (10) according to any one of items 1 to 56, wherein the vial (110) exhibits a central longitudinal axis "A" and the reservoir (120) exhibits a central longitudinal axis "B", and the vial and reservoir mounting openings (111, 121) are arranged to hold the vial (110) and reservoir (120) in a position where the central longitudinal axes "A" and "B" are arranged at an angle of less than 75°, preferably less than 60°, more preferably less than 50°, or even less than 20°, for example 0°.

[0173] 58. The longitudinal central axes "A" and "B" are positioned between 20° and 0°, preferably between 10° and 0°, more preferably between 5° and 0°, e.g., at 0°, or 58. The pharmaceutical mixing system (10) according to item 57, wherein the central longitudinal axes "A" and "B" are arranged at an angle between 70° and 20°, or between 60° and 30°, or between 50° and 40°, for example 45°.

[0174] 59. A drug mixing system (10) according to item 57 or 58, wherein the vial and reservoir mounting openings (111, 121) of the adapter (100) are arranged such that at least the central longitudinal axis "A" of the vial, and optionally both the central longitudinal axes "A" and "B" of the vial and reservoir, are arranged vertically or essentially vertically during use.

[0175] 60. The drug mixing system (10) of any one of items 1 to 59, wherein the adapter (100), and optionally the drug mixing system (10), is sterilizable.

[0176] 61. The drug mixing system (10) according to item 60, wherein the adapter (100), and optionally the drug mixing system (10), are sterilizable in their packaged state.

[0177] 62. The drug mixing system (10) according to item 60 or 61, wherein the adapter (100), and optionally the drug mixing system (10), is sterilizable with ethylene oxide and / or gamma irradiation.

[0178] 63. The drug mixing system (10) of any one of items 1 to 62, wherein the adapter (100), and optionally the drug mixing system (10), are stored and delivered pre-packaged and sterile.

[0179] 64. A drug mixing system (10) according to any one of items 1 to 63, wherein the vial (110) and reservoir (120) are pre-assembled within the vial mounting opening (111) and reservoir mounting opening (121), respectively, of the adapter (100) of the drug mixing system (10).

[0180] 65. A drug mixing system (10) according to any one of items 2 to 64, wherein the drug mixing system (10) is a valve-type drug mixing system (10b) having a liquid retaining means (145) in the form of a switch valve (150), and the adapter (100), and optionally the drug mixing system (10), are stored and delivered in a pre-packaged state with the switch valve (150) of the adapter (100) in valve position 1.

[0181] 66. A pharmaceutical mixing system (10) according to any one of items 1 to 65, wherein the formulation (110a) in the vial (110) is provided in powder form, such as a powder for reconstitution, or as a liquid.

[0182] 67. A pharmaceutical mixing system (10) according to any one of items 1 to 66, wherein the formulation (110a) in the vial (110) is provided in lyophilized form.

[0183] 68. A drug mixing system (10) according to any one of items 1 to 67, wherein the formulation (110a) in the vial (110) is provided as a liquid, the liquid being a drug concentrate and / or liquid solubilisate.

[0184] 69. A drug mixing system (10) according to any one of items 1 to 68, wherein the formulation (110a) in the vial (110) comprises at least one drug, optionally a combination of drugs.

[0185] 70. The drug mixing system (10) of any one of items 1 to 69, wherein the liquid in the reservoir (120) is a pharmaceutically acceptable liquid.

[0186] 71. The drug mixing system (10) according to item 70, wherein the pharmaceutically acceptable liquid is an injectable liquid such as water for injection (aqueous injection) and / or an inhalable liquid.

[0187] 72. The drug mixing system (10) according to any one of items 1 to 71, wherein the drug mixing system is intended for single use.

[0188] 73. An adapter (100) for a drug mixing system (10) according to any one of items 1 to 72.

[0189] 74. The adapter (100) according to item 73, wherein the adapter (100) comprises piston locking means (126) adapted to lock the position of the piston (125) once a predetermined amount of liquid has been transferred from the reservoir (120) into the vial (110) by forcing the piston (125) into the housing (124), thereby creating and storing an overpressure.

[0190] 75. An adapter (100) according to item 73 or 74, wherein the adapter (100) comprises a stabilizing wall (170) externally surrounding or encasing at least a portion of the reservoir housing (124), said stabilizing wall (170) being dimensionally stable to support and stabilize the reservoir (120) within the adapter (100) while forcing the piston (125) into the housing (124) and generating an overpressure.

[0191] 76. A method for preparing a dissolved or diluted formulation (110b), optionally a drug solution, from a formulation (110a) stored in a vial (110), comprising: a) providing a pharmaceutical mixing system (10) according to any one of items 1 to 72; b) transferring a predetermined amount of liquid from the reservoir (120) into the vial (110) by pushing the piston (125) into the housing (124) while the liquid retaining means (145) blocks the flow of at least the dissolved or diluted formulation (110b) through the outlet port (130), thereby creating an overpressure and a mixture of the formulation (110a) and the liquid; c) once a predetermined amount of liquid has been transferred from the reservoir (120) to the vial (110), locking the piston (125) in place with the piston locking means (126), thereby storing the overpressure created in step b; d) dissolving or diluting the mixture of formulation (110a) and liquid resulting from steps b) and c) to the desired extent, optionally assisting this dissolving or diluting process by vibrating the drug mixing system (10); e) using the stored overpressure generated in steps b) and c) to expel or transfer the dissolved or diluted formulation (110b) from the vial (110) through the outlet port (130) by actuating the liquid expelling means (155, 255), thereby forcing the piston (125) into the housing (124) and locking the piston (125) in place.

[0192] 77. A method for preparing a dissolved or diluted formulation (110b), optionally a drug solution, from a formulation (110a) stored in a vial (110) according to item 76, comprising: a) providing a valve-type drug mixing system (10b) according to any one of applicable items 2 to 72, wherein the liquid retaining means (145) is provided in the form of a switch valve (150), the internal adapter channel (140) and the switch valve (150) being adapted to at least allow selective fluid connection between the vial (110) and the reservoir (120) while blocking the fluid connection to the outlet port (130) when in valve position 1, and to allow selective fluid connection between the vial (110) and the outlet port (130) while blocking the fluid connection to the reservoir (120) when in valve position 2; b) with the switch valve (150) in or placed in valve position 1, transferring a predetermined amount of liquid from the reservoir (120) into the vial (110) by forcing the piston (125) into the housing (124), thereby creating an overpressure and a mixture of the formulation (110a) and the liquid; c) once a predetermined amount of liquid has been transferred from the reservoir (120) to the vial (110), locking the piston (125) in place with the piston locking means (126), thereby storing the overpressure created in step b; d) dissolving or diluting the mixture of formulation (110a) and liquid resulting from steps b) and c) to the desired extent, optionally assisting this dissolving or diluting process by vibrating the drug mixing system (10); e) using the stored overpressure generated in steps b) and c) by placing the switch valve (150) in valve position 2, thereby forcing the piston (125) into the housing (124) and locking the piston (125) in place, to expel or transfer the dissolved or diluted formulation (110b) from the vial (110) through the outlet port (130).

[0193] 78. A method for preparing a dissolved or diluted formulation (110b), optionally a drug solution, from a formulation (110a) stored in a vial (110) according to item 76, comprising: a) providing a seal-type drug mixing system (10a) according to any one of applicable items 2 to 72, wherein the liquid retaining means (145) is provided in the form of a septum (131) covering the outlet port (130), and the liquid releasing means (155, 255) is provided in the form of a septum piercing means (230); b) transferring a predetermined amount of liquid from the reservoir (120) into the vial (110) by pushing the piston (125) into the housing (124) while the septum (131) blocks the flow of at least the dissolved or diluted formulation (110b) through the outlet port (130), thereby creating an overpressure and a mixture of the formulation (110a) and the liquid; c) once a predetermined amount of liquid has been transferred from the reservoir (120) to the vial (110), locking the piston (125) in place with the piston locking means (126), thereby storing the overpressure created in step b; d) dissolving or diluting the mixture of formulation (110a) and liquid resulting from steps b) and c) to the desired extent, optionally assisting this dissolving or diluting process by vibrating the drug mixing system (10); e) using the stored overpressure generated in steps b) and c) to release or transfer the dissolved or diluted formulation (110b) from the vial (110) through the outlet port (130) by actuating the liquid releasing means (155, 255) by puncturing the septum (131) with the septum puncturing means (230), thereby forcing the piston (125) into the housing (124) and locking the piston (125) in place.

[0194] 79. The method of any one of items 76 to 78, wherein a drug mixing system (10) of any one of items 38 to 71 is provided in step a, and the drug mixing system (10) is activated by moving the adapter (100) from a rest position to an activated position.

[0195] 80. The method of item 79, wherein the adapter (100) is brought from the rest position to the working position by shifting the first and second adapter subunits (101, 102) of the adapter (100) toward each other.

[0196] 81. The method according to item 79 or 80, wherein the first and second adapter subunits (101, 102) of the adapter (100) can be shifted towards each other with one hand.

[0197] 82. The method according to any one of items 76 to 81, wherein the dissolved or diluted formulation (110b) is transferred from the vial (110) through the outlet port (130) into a receiving device (200) for receiving the dissolved or diluted formulation (110b) from the vial (110).

[0198] 83. The method according to any one of items 76 to 82, wherein the adapter (100) according to any one of items 73 to 75 is provided separately from the vial (110) containing the formulation and / or the reservoir (120) for containing a liquid for dissolving or diluting the formulation, and the vial (110) and / or the reservoir (120) are then coupled to the respective vial mounting opening and reservoir mounting opening (111, 121) of the adapter (100) to provide the drug mixing system (10) of method step a).

Claims

1. A pharmaceutical mixing system (10) for dissolving or diluting a pharmaceutical preparation (110a) stored in a vial (110) prior to use, said pharmaceutical mixing system (10) comprising: an adapter (100) adapted to hold the vial (110) containing the pharmaceutical preparation (110a); and a reservoir (120) for containing a liquid (120a) for dissolving or diluting the pharmaceutical preparation (110a), said reservoir (120) comprising a housing (124) and a piston (125) sealingly movable within said housing (124); The adapter (100) a vial mounting opening (111) adapted to hold said vial (110); a reservoir mounting opening (121) adapted to hold said reservoir (120); an outlet port (130); an internal adapter channel (140) fluidly connecting the vial mounting opening (111) and the reservoir mounting opening (121) with the outlet port (130); a liquid retaining means (145) adapted to block the flow of at least the dissolved or diluted formulation (110b) through said outlet port (130); the adapter (100) comprises a piston locking means (126) adapted to lock the position of the piston (125) when a predetermined amount of the liquid is transferred from the reservoir (120) into the vial (110) by forcing the piston (125) into the housing (124), thereby creating and storing an overpressure; the drug mixing system (10) is adapted to expel or transfer the dissolved or diluted formulation (110b) from the vial (110) through the outlet port (130) when a liquid discharging means (155, 255) is activated using the overpressure generated by forcing the piston (125) into the housing (124).

2. a) for a seal-type drug mixing system (10a), said liquid retaining means (145) is provided in the form of a septum (131) covering said outlet port (130); the liquid discharge means (155, 255) is provided in the form of a septum piercing means (230) whereby, upon actuation, the septum (131) is pierced by the septum piercing means (230) and the dissolved or diluted formulation (110b) is expelled or transferred from the vial (110) through the outlet port (130) using the overpressure created by forcing the piston (125) into the housing (124); or b) for a valve-type drug mixing system (10b), the liquid retaining means (145) is provided in the form of a switch valve (150), optionally a rotatable or movable switch valve (150r, 150s), wherein said internal adapter channel (140) and said switch valve (150) are adapted to at least allow a selective fluid connection between said vial (110) and said reservoir (120) while blocking the fluid connection to said outlet port (130) when in valve position 1, and to allow a selective fluid connection between said vial (110) and said outlet port (130) while blocking the fluid connection to said reservoir (120) when in valve position 2; the liquid discharging means (155, 255) is provided in the form of a switch valve operating means (156) adapted to, upon actuation, place the switch valve (150) in valve position 2, whereby, when the switch valve (150) is placed in valve position 2, the dissolved or diluted formulation (110b) is expelled or transferred from the vial (110) through the outlet port (130) using the overpressure created by forcing the piston (125) into the housing (124); The pharmaceutical mixing system (10) of claim 1.

3. 3. The pharmaceutical mixing system (10) of claim 1 or 2, wherein the dissolved or diluted formulation (110b) is transferred from the vial (110) through the outlet port (130) into a receiving device (200), optionally a nebulizer (201), further optionally a vibrating mesh nebulizer (202), for receiving the dissolved or diluted formulation (110b) from the vial (110).

4. The drug mixing system (10) of any one of claims 1 to 3, wherein the adapter (100) and the receiving device (200) respectively comprise a connecting means (160) and a connecting means (260) for connecting the drug mixing system (10) to the receiving device (200), and preferably the connecting means (160) and the connecting means (260) are adapted to activate the liquid releasing means (155, 255) when they are connected.

5. The connecting means (160) and the connected means (260) the septum piercing means (230) is adapted to automatically pierce the septum (131) when the seal-type drug mixing system (10a) and the receiving device (200) are connected; wherein connecting the valve-type drug mixing system (10b) to the receiving device (200) automatically places the switch valve (150) in valve position 2, optionally via physical interaction of the connecting means (160) and / or the connected means (260) with the switch valve operating means (156) of the adapter (100b).

5. The pharmaceutical mixing system (10) of claim 4, adapted for:

6. the switch valve operating means (156) is part of the adapter (100b) of the valve-type drug mixing system (10b); The switch valve operating means (156) is provided in the form of a protrusion (156a) such as a push button protruding from the male connection means (160m) of the adapter (100b), The male connecting means (160m) is insertable into the female connecting means (260f) of the receiving device (200), When the male connecting means (160m) is inserted into the female connecting means (260f), the protruding switch valve operating means (156a) is pushed into the male connecting means (160m), thereby moving the switch valve (150) to valve position 2, and the dissolved or diluted formulation (110b) is expelled or transferred from the vial (110) through the outlet port (130) to the receiving device (200) using the overpressure. A pharmaceutical mixing system (10) according to claim 5.

7. For a sealed-type drug mixing system (10a), the liquid discharging means (155, 255) is provided in the form of a septum piercing means (230), and the liquid discharging means (155, 255) is provided as part of the receiving device (200); Optionally, the septum piercing means (230) is located at the center of a spoked-wheel-shaped portion (220) located at the inlet opening (210) of the receiving device through which the dissolved or diluted formulation (110b) is received. A pharmaceutical mixing system (10) according to any one of claims 3 to 5.

8. 8. A pharmaceutical mixing system (10) according to any one of claims 1 to 7, wherein the piston locking means (126) is provided in the form of an engaging hook (126a) or a plurality of engaging hooks (126a, 126a', 126a", etc.), a ratchet mechanism or similar snap-fit ​​locking mechanism (126c), or a plurality of ratchet mechanisms or similar snap-fit ​​locking mechanisms (126c, 126c', 126c", etc.).

9. 9. The drug mixing system (10) of claim 1, further comprising a stabilizing wall (170) externally surrounding or encasing at least a portion of the reservoir housing (124), the stabilizing wall (170) being dimensionally stable to support and stabilize the reservoir (120) within the adapter (100) while forcing the piston (125) into the housing (124) and generating the overpressure.

10. 10. The drug mixing system (10) of claim 1, wherein the adapter (100) further comprises a piston guide means (127) for forcing the piston (125) into the housing (124) and enabling controlled and stable movement of the piston (125) within the housing (124) while generating the overpressure.

11. 11. The drug mixing system (10) of claim 2, wherein the drug mixing system (10) is a valve-type drug mixing system (10b) having a liquid holding means (145) in the form of a switch valve (150), the switch valve (150) being a three-way switch valve having three openings for selectively enabling fluid connection between the vial mounting opening (111), the reservoir mounting opening (121), and the outlet port (130).

12. 12. A pharmaceutical mixing system (10) as claimed in any one of claims 1 to 11, wherein the vial (110) exhibits a central longitudinal axis "A", the central longitudinal axis "A" being oriented vertically or essentially vertically during use.

13. A drug mixing system (10) as described in any one of claims 1 to 12, wherein the vial (110) and the reservoir (120) are pre-assembled within the vial mounting opening (111) and the reservoir mounting opening (121), respectively, of the adapter (100) of the drug mixing system (10).

14. An adapter (100) for a drug mixing system (10) according to any one of claims 1 to 13.

15. 1. A method for preparing a dissolved or diluted formulation (110b), optionally a drug solution, from a formulation (110a) stored in a vial (110), comprising: a) providing a pharmaceutical mixing system (10) according to any one of claims 1 to 13; b) transferring a predetermined amount of the liquid from the reservoir (120) into the vial (110) by pushing the piston (125) into the housing (124) while the liquid retaining means (145) blocks the flow of the dissolved or diluted formulation (110b) through at least the outlet port (130), thereby creating an overpressure and a mixture of the formulation (110a) and the liquid; c) once the predetermined amount of liquid has been transferred from the reservoir (120) to the vial (110), locking the piston (125) in place with the piston locking means (126), thereby storing the overpressure created in step b; d) dissolving or diluting the mixture of formulation (110a) and liquid resulting from steps b) and c) to the desired extent, optionally assisting this dissolving or diluting process by vibrating the pharmaceutical mixing system (10); e) using the stored overpressure created in steps b) and c) by actuating the liquid releasing means (155, 255), thereby forcing the piston (125) into the housing (124) and locking the piston (125) in place, to release or transfer the dissolved or diluted formulation (110b) from the vial (110) through the outlet port (130).

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