WO2014145959A1

WO2014145959A1 - Portable detachable drug mixing and delivery system and method

Info

Publication number: WO2014145959A1
Application number: PCT/US2014/030818
Authority: WO
Inventors: Brent Buchine; Christopher STEPANIAN
Original assignee: Windgap Medical, Inc.
Priority date: 2013-03-15
Filing date: 2014-03-17
Publication date: 2014-09-18

Abstract

A system and method stores a dry medicament component and then mixes with a wet component for delivery to a user. The drug delivery system has a mixer body having a series of walls defining a channel and an interior flow chamber. The mixer body has an inlet and an outlet. The interior flow chamber is adapted to receive a dry medicament component. The system also includes a liquid containment assembly having an interior chamber. The interior chamber includes a wet compartment configured to store a wet component. The wet component is capable of mixing with the dry medicament component in the mixer body.

Description

Portable Detachable Drug Mixing and Delivery System and Method

CROSS-REFERENCE TO RELATED APPLICATIONS

[001] This application claims the benefit of U.S. Patent Application 61/800,258 filed on March 15, 2013, which is incorporated herein by reference.

FIELD OF THE INVENTION

[002] The present invention relates to a drug storage assembly and more particularly to a mixer that enables the storage, reconstitution, and injection of one or more compounds, the "dry", to the stream of diluent, the "wet", in the compact and mechanically simple drug delivery device.

BACKGROUND OF THE INVENTION

[003] The efficacy of drugs is influenced by several factors; including exposure to heat or cold, ultraviolet light, and other forms of radiation; materials of contact; and time since manufacture, which allows the factors to grow in impact.

[004] In addition to the efficacy and the storage requirement regarding temperature, the size of the drug storage assembly and delivery system is a factor in shipping and storage; this is especially true in the developing world. A typical drug autoinjector like the EpiPen^® in its protective case is 6.25" x 1.25" x 1.25" and is capable of delivering only one dose of pharmaceuticals to one patient. A device the size of a USB drive utilizing a thermally-stable drug would enable easier transport of a larger number of doses per shipment, simplifying logistics. SUMMARY OF THE INVENTION

[005] It has been recognized that if components of a drug can be separated until the drug is needed, the components in separate states can be stored for a longer time than the reconstituted drug.

[006] In an embodiment of a drug delivery system, the system has a mixer body having a series of walls defining a channel and an interior flow chamber. The mixer body has an inlet and an outlet. The interior flow chamber is adapted to receive a dry medicament component.

[007] In an embodiment, the system also includes a liquid containment assembly having an interior chamber. The interior chamber includes a wet compartment configured to store a wet component. The wet component is capable of mixing with the dry medicament component in the mixer body.

[008] In an embodiment, the syringe assembly has an interior chamber. The interior chamber includes a wet compartment configured to store a wet component. The wet component is capable of mixing with the dry medicament component in the mixer body.

[009] In an embodiment, the syringe assembly and the mixer body each have a compatible syringe connection.

[010] In an embodiment, the system includes an injection needle that is detachably connected to the outlet portion of the mixer body. In another embodiment, the injection needle is permanently attached to the mixer body.

[011] In an embodiment, the mixer body is sized to define a hollow volume sized to the dry medicament component received. In an embodiment, the series of walls of the mixer body define a tortious path for carrying the dry medicament component. The tortious path of the mixer body also defines the volume for mixing the wet component with the dry medicament. In an embodiment, the tortious path defines a flow regime for mixing the wet component with the dry medicament. In an embodiment, the tortious path defines a turbulent flow for mixing the wet component with the dry medicament.

[012] In an embodiment, the series of walls of the mixer body define a chaos -inducing flow path for carrying the dry medicament component and define the volume for mixing the wet component with the dry medicament.

[013] In an embodiment, at least one of the dimensions in the channel in the mixer is less than 2 millimeters. In an embodiment, the Reynolds number in the mixer during mixing is less than 2300. In an embodiment, the Reynolds number in the mixer during the mixing is less than 100. In an embodiment, the Reynolds number in the mixer during the mixing is less than 10. In an embodiment, the Reynolds number in the mixer during mixing is greater than 2300.

[014] In an embodiment, the mixing assembly includes a plurality of grooves formed therein. The grooves facilitate mixing through chaotic flow when a wet component flows by the grooves.

[015] In an embodiment, the interior flow chamber of the mixer body is kept in vacuum until the mixer body is attached to the liquid-filled syringe. The mixer body has a failure membrane that fails upon the syringe engaging the mixer body. In an embodiment, the mixer body has a gas vent structure to ensure that gas trapped in the mixer is vented.

[016] In an embodiment of an injection device containing a pre-loaded charge of medicament for administering the medicament upon actuation, the injection device has a syringe assembly having an interior chamber. The interior chamber includes a wet compartment configured to store a wet component. A mixing assembly is detachably connected to the housing assembly. The mixing assembly defines an inlet configured to connect with the syringe assembly, an outlet, and an interior chamber having a volume. A portion of the mixing assembly contains a dry medicament component configured to mix with the wet component as a result of activation of the syringe assembly. The injection device includes an injection needle detachably connected to the outlet portion of the mixing assembly.

[017] In an embodiment of a method of assembling an injection device, a dry medicament component is inserted into a portion of a mixer body having an interior flow chamber. A wet component is passed through the interior flow chamber of the mixer body to mix the wet component with the dry medicament component. A syringe is configured to be detachably connected to the interior chamber. The mixing assembly is in fluid communication with the interior chamber upon activation of the device. An injection needle is attached to deliver the combined medicament.

[018] In an embodiment, the wet component is pulled into the syringe through the mixer body. The mixer body is removed from the syringe. The injection needle is attached to the syringe after mixing occurs.

[019] In an embodiment, the syringe contains the wet component prior to connection to the mixer body. The mixing occurs as the wet component passes through the mixer body to the injection needle for delivery.

[020] These aspects of the invention are not meant to be exclusive and other features, aspects, and advantages of the present invention will be readily apparent to those of ordinary skill in the art when read in conjunction with the following description, appended claims, and accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

[021] The foregoing and other objects, features, and advantages of the invention will be apparent from the following description of particular embodiments of the invention, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention.

[022] FIG. 1 is a schematic of a system of creating a drug and injection according to the invention;

[023] FIG. 2 is a schematic of a syringe, a mixer, and a needle according to the inventions;

[024] FIG. 3 is a chart showing the dosage concentration versus time as mixing;

[025] FIG. 4 is a sectional view of an enlarged portion of the mixer;

[026] FIG. 5 is a top view of the mixer with a portion broken away;

[027] FIG. 6 is a bottom view of the mixer showing an air stripper membrane vapor separator;

[028] FIG. 7A is a sectional view of an enlarged portion of an alternative embodiment of the mixer with a single microchannel;

[029] FIG. 7B is a sectional view of an enlarged portion of an alternative embodiment of the mixer with a single straight microchannel; [030] FIG. 7C is a sectional view of an enlarged portion of an alternative embodiment of the mixer;

[031] FIG. 8 is sectional view of an enlarged portion of a mixer with vacuum and seal; [032] FIG. 9 is a schematic of a syringe, a mixer, and a wet component storage container;

[033] FIG. 10 is a schematic of an alternative embodiment of a syringe, a mixer, and a second component storage container;

[034] FIG. 11 is a schematic of another alternative embodiment of a syringe, a mixer, and a second component storage container;

[035] FIG. 12 is a schematic of an alternative embodiment that has a housing for holding the dry medicament;

[036] FIG. 13 is a schematic of an alternative embodiment that has a syringe holding both the dry medicament and the wet component separated by a membrane; [037] FIG. 14A is a schematic of an alternative embodiment having a dry medicament container connectable to an alternative style syringe;

[038] FIG. 14B is an exploded view of the dry medicament container and the syringe of FIG. 14A; and

[039] FIG. 15 is a schematic of an alternative embodiment system having a pair of wet component containers.

DETAILED DESCRIPTION OF THE INVENTION

[040] A system and method for storing a dry medicament component and then mixing with a wet component for delivery to a user. The drug delivery system has a mixer body having a series of walls defining a channel and an interior flow chamber. The mixer body has an inlet and an outlet. The interior flow chamber is adapted to receive a dry medicament component. The system also includes a liquid containment assembly having an interior chamber. The interior chamber includes a wet compartment configured to store a wet component. The wet component is capable of mixing with the dry medicament component in the mixer body.

[041] For purposes of this application a dry or wet medicament component refers to any component that can be used for mixing, dissolving, reconstituting, suspending, reactivating, reacting, diffusing, liquefying, combining, blending, intermixing, homogenizing, emulsifying, chemically altering, buffering, or equivalents with another dry or wet component. For example, the dry medicament component may only need water as a diluent in order to deliver the diluted dry component into a subject. In other examples, the wet component acts as a reagent when combined with the dry medicament component.

[042] Referring to FIG. 1, a schematic of a system 20 of creating a drug and injection according to the invention is shown. The system 20 has a mixer 22 in which a dry medicament component 24 and a wet component 26 are mixed. The dry medicament component 24 and the wet component 26 form a combined medicament 28 which is injected using an injector 30 into a user 32. While the dry medicament component 24 and the wet component 26 are showed joining together at the mixer 22, the wet component 26 passes through the dry medicament component 24 to form the combined medicament 28.

[043] In certain embodiments, the system 20 has an additional wet component 34 that is added to the mixer after the first wet component 26. The system 20 allows the dry medicament component 24 to be stored separately in a compact container until needed and then mixed with the wet component 26; the mixing occurs as explained below by passing the wet component 26 through the dry medicament component 24.

[044] Referring to FIG. 2, a schematic of the system 20 with a syringe 40, the mixer 22, and the injector 30 is shown. The syringe 40 has a cylindrical tube 42 defining a volume 44. The cylindrical tube 42 of the syringe 40 tapers down to an outlet port 48. The syringe 40 has a plunger 50 with a depressing handle 52, a shaft 54, and a piston 56 for forcing the wet component 26 out of the outlet port 48.

[045] While the syringe 20 is shown separated from the mixer 22 in FIG. 2, the syringe 40 and the mixer 22 are connected prior to use as explained below. The injector 30 which is shown as a needle 60 can be connected to the mixer 22 or the syringe 40 dependent on the mode. The injector 30 can be also be a nozzle or tubing for delivery of the mixed combined medicament 28.

[046] The mixer 22 has a housing 64 that defines an interior flow chamber 66 with an inlet 68 and an outlet 70. The interior flow chamber 66 of the mixer 22 has a plurality of internal walls 72 defining channels 74. The internal walls 72 includes all the walls including side, bottom, and top walls. The channels 74 contain the dry component 24. The wet component 26 is passed through the channels of the mixer 22 to mix with the dry component 24 to form a solution of component 24 dissolved in component 26 to form the final combined medicament 28.

[047] In an embodiment, the sterile, "dry" filled wet/dry mixer 22 would be attached to the syringe 40 by a coupling such as a syringe connector, a Luer connector, a Luer taper fitting. This drug mixing device, the mixer 22, could either have an additional coupling on the other end such as a Luer taper capable of attaching the syringe needle 60 of the user's choice or a permanently affixed needle, suitable for the injection of the dry drug pre-loaded into the "dry" filled wet/dry mixer 22.

[048] Referring to FIG. 3, a chart showing the dosage concentration versus time as mixing. In certain embodiments, the liquid diluent, a wet component, is pushed through the wet/dry mixer 22 and out the needle 60; this will likely result in a variation in concentration of the reconstituted drug coming out the tip of the needle 60 over time, during the duration of the injection.

[049] Assuming the drug concentration is asymptotic, the majority of the drug will be reconstituted and delivered during the onset of the plunger 50 stroke, the left side of the graph. Assuming consistency of function, the quantity of drug being delivered 80 to patients, the user 32, with each injection would be consistent since the majority, 90%+ of that drug would be delivered in first half of the plunger 50 stroke, ensuring sufficient dosing.

[050] The system 20 is designed to deliver the required potency with the required confidence. For example regulatory authorities are looking for a 95% confidence interval that the targeted dosage will be delivered.

[051] Referring to FIG. 4, a sectional view of an enlarged portion of the mixer 22 is shown. The outlet port 48 of the syringe 40 is received by the inlet 68 of the mixer 22. The wet component 26 flows through the channels 74 formed by the housing 64 and the interior walls 72. The channels 74 contain the dry component 24. The flow of the wet component 26 through the tortious path of the channels 74 results in the mixture of the wet component 26 with the dry component 24 to form the combined medicament 28. The shape and structure of the channels 74 causes chaotic flow in the case of laminar wet component 26 flow. If chaotic flow may be achieved through the channels 74, this provides suitable mixing.

[052] In an embodiment, at least one dimension in the channel is less than 2 millimeters which mixes the dry component 24 into the wet component 26 where the Reynolds number in the diluent is less than 100, relying on chaotic mixing. An example of this could be a series of structures where at least one dimension in the channel is less than 2 millimeters which mixes the dry drug into the diluent where the Reynolds number in the diluent is less than 10, relying on chaotic mixing. In an embodiment, the channel has the characteristics such that the Reynolds number in the diluent is less than 2300. In certain embodiments it might be desirable to have a Reynolds number over 2300 and under 4000 or having a Reynolds number greater 4000. In certain embodiments it might be desirable to create turbulent mixing.

[053] The dry component 24 can be retained in the channels 74 by various methods. The dry component 24 can be evaporated onto the walls 72 of the channel 74; for example the volumetric spotting of known concentration liquid can be placed on the walls 72. Another method is the dry component 24 is placed in the channels 74 in a granular / powder form 84, as best seen in FIG. 5; a filter 86 prevents the dry component 24 from leaving the mixer 22 in solid form from either the inlet 68 or the outlet 70.

[054] Referring to FIG. 5, a top view of one embodiment of the mixer 22 with a portion of the housing 64 broken away is shown. The inlet 68 with an opening 90 that in the housing 64 of the mixer 22 allows the wet component 26 to enter into the interior flow chamber 66. The wet component 26 flows first radially outwards towards the outer wall 88. The walls 72 of the channel 74 in this embodiment have a series of protrusions 96, one shown, and a plurality of wells 98 to create turbulence to increase the interaction between the wet component 26 and the dry component 24. The interior walls 72, which in addition to the outer wall 88 define the channels 74, have both a plurality of plates 104 that are planar to the top, inlet, surface and the bottom, the outlet, surface and a series of ribs 106 to support the plates 104.

[055] In an example of the embodiment, the syringe 40 is a 1 mL syringe body, filled with 1 mL of sterile water with a Luer-Lock fitting. The mixer 24 and the injector 30 are one unit, a drug-containing needle/mixing body consisting of a plastic fitting with microfluidic mixing channels containing 1 mg of dry drug and a Luer-Lock fitting. The drug is completely water soluble at concentrations much greater than lmg/mL. The needle is capped with a safety cap.

[056] The syringe 40 and the mixer 22 are connected by their Luer-Lock fittings. The needle safety cap is removed. The syringe is driven into the patient at an appropriate injection point such as their deltoid muscle, their outer thigh, into a vein, or other desired spot. The depth of the injection could also be varied to include intradermal, subcutaneous, intramuscular, intravenous, intraosseous, intraperitoneal, intrathecal, epidural, intracardiac, intraarticular, intracavernous, and intravitreal. Each type of injection is best served by a different drug, quantity of drug, location or series of locations where the drug is best administered, and depth of injection. This is well known to those skilled in the art.

[057] The plunger is depressed by the caregiver, driving the fluid through the drug- containing needle/mixing body, out the tip of the needle and into the patient. [058] In alternative to the caregiver, the motive force could be other mechanisms such as autoinjectors or syringe pumps.

[059] Referring to FIG. 6, a bottom view of a mixer 22 showing an air stripper membrane vapor separator 110 is shown. In an embodiment that has the dry component 24 in the mixer 22 in an environment of air from the packaging location, there is a concern that air may enter the user 32. The concern regarding air entering the user is dependent in part on the drug. The concern is bubbles that enter the blood system in an intra-venous injection in certain situations may be harmful to the user of the drug. In contrast, air injected under the skin or into a muscle is acceptable by the FDA and other regulating bodies, as is air injected into the epidural space.

[060] Still referring to FIG. 6, the mixer 22 has a series of openings 112 in the housing 64. The openings 112 have the air stripper membrane 110 which allows the air to pass out of the mixer 22 but retains the dry component 24, the wet component 26, and the combined medicament 28. A mechanical vent could also be used that closes when liquid is present.

[061] Referring to FIGS. 7 A - 7C, several types of detachable mixers 700a-c are contemplated. In contrast to cylindrical mixer embodiment shown in FIGS 2, 4, 5, and 6, the embodiments shown in FIGS. 7 A - 7B is a planar mixer.

[062] Referring to FIG. 7A, a sectional view of an enlarged portion of an alternative embodiment of a mixer 700a with a single channel, such as a microchannel 124, is shown. The microchannel 124 of the mixing device 700a is a serpentine channel, which defines a fluid pathway between the inlet 68 and the outlet 70. It should be understood that the inlet 68 and the outlet 70 may also be referred to as openings to the mixer, as fluid may enter in and out of the outlet 70 as well as the inlet 68. The serpentine channel 124 has two functions; the first function is that enables miniaturization of the channel structure by bending the fluid flow direction so that the channel can double back, thus a longer channel more efficiently utilizes a smaller area. The second function is that the natural flow becomes disrupted every time there is a bend or elbow in the channel, which results in mixing dependent on the cross section of the channel. These serpentine channels may consist of small or large radius turns, or a combination thereof. This may include turn radi that approach 0 millimeters resulting in turns that approach 180 degrees (not shown).

[063] Each embodiment will result in different mixing properties that can enable control over the quantity and quality of mixing. This may be important given that certain drug compounds are sensitive to shear whereas other compounds may require a more aggressive mixing device. This variability in tuning the mixing conditions allows for desired wet and dry components to be used in an autoinjector device as control is one key performance attribute of the present application.

[064] Referring to FIG. 7B, a sectional view of an enlarged portion of an alternative embodiment of the mixer 700b with a single straight microchannel 128 is shown.

Dependent on the wet and dry components, a straight microfluidic channel configured with parallel walls may be sufficient to mix wet and dry components. Dry components stored inside a portion of the microfluidic channel may act to break up the laminar flow within the channel and create chaotic mixing until driven into solution.

[065] When the liquid moves through the channel and begins to push into the dry component contained in a portion therein, the flow front will cause chaotic flow. In order to make this happen, the channel dimension, which, in one embodiment can be defined by a square cross-section, should be below a certain size. For this embodiment and many of the embodiments described herein, one or more sides of the channel cross-section may have a dimension less than 2mm, between 1mm and 2mm, between 1mm and 500um, less than 500um, between 250um and 500um, or less than 250um, or between lOOum and 250um, or less than lOOum, or between 50um and lOOum, or less than 50um, or between lOum and 50um, or less than lOum, or between lum and lOum, or less than lum. For purposes of this application, channels having a cross-sectional dimension less than lum are considered to be nanofluidic and have their respective set of properties for mixing medicaments. In certain embodiments, it might be desirable to have a dimension greater than 2 mm.

[066] Referring to FIG. 7C, it is recognized that the drug mixing system 700c can having multiple conduits or channels and seals. A sectional view of an enlarged portion of an alternative embodiment of the mixer 122 is shown in FIG. 7C. In contrast to the embodiment shown in FIGS. 4 and 5, the cross sectional area of each channel 124 is generally the same size. The mixer 122 has an inlet 68 which opens into an inlet void 126. A plurality of channels 124 start at the inlet void 126 and end in an outlet void 128 at the outlet 70. Each of the channels 124 has a circuitous path 130 with various radiuses and chaos -inducing features. Each channel 124 can have variations in the cross sectional area and characteristics on the walls of the channel 124 to cause the flow of the wet component 26 to mix thoroughly with the dry medicament component 24. Chaos- inducing features can include grooves perpendicular to the flow path, pits, channels that change in cross section, recombining points. The walls and features could be produced by machining, molding, embossing, or other manufacturing techniques.

[067] The number and the style of the channel can be tailored to the particular dry medicament component, the wet component, and the desired combined medicament. For example the channel can be straight, have bends, serpentine, herringbone, and saw-like tooth pattern. In addition, the size of channel can have cross sectional area having dimensions of one or more sides of the channel cross-section or diameter of a channel that has dimension less than 2mm, less than 1 mm or greater than 2 mm dependent on the specific dry medicament component, the wet component, and the desired combined medicament and the configures of the channel.

[068] The mixer 122 can allow for two different types of medicaments (or two doses of the same) to be mixed and inserted into a person using a single needle or other delivery system. A seal can span the orifices of each storage cavity which are each in fluid communication with a different channel contained within the mixing device. These channels may vary in length and size enabling a time mixing/release of each medicament. For example, a first wet component stored in a volume enters a unique channel(s) that has a pathway shorter than the unique channel(s) the second wet component stored in are in fluid communication with. The first wet component mixes with the first dry component, homogenizes (in this embodiment, but not all embodiments), enters the needle assembly and is injected into a person, where the second wet component takes longer to mix with the second dry component and follows after the first mixed medicament has entered the needle assembly to be injected into the person after. This is useful for two medicaments that are not compatible to be stored in the same portions of the mixing assembly and/or reconstituted or mixed together in the same channel.

[069] The mixer 22, 122, 700a, or 700b is sized and tailored on several factors including the particular the dry medicament component, the wet component, and the combined medicament. The tailoring can include the overall volume relative to the dry medicament component volume, location of the dry medicament component in the mixer, and the type of channel. The location of the dry medicament component is dependent in the particular embodiment and the process.

[070] Another alternative is to have valving for multiple, such as five, doses of the same or different dry medicament. The valving allows fluid flow through one or more channels containing dry medicament component but not all of the channels enabling formulation and dosing variability for the combined medicament. The valves can be passive or actively controlled.

[071] U.S. Patent Application 13/529,757 filed on June 21, 2012 and published a published patent application US 2013/0178823 on July 11, 2013 describes additional designs of channels and are incorporated herein by reference.

[072] Referring to FIG. 8, a sectional view of an enlarged portion of a mixer 22 with a vacuum seal and a syringe 40 is shown. The inlet 68 of the mixer 22 has a seal 140 that maintains a vacuum within the channels 74 that hold the dry component 24. When the syringe 40 is connected to the mixer 22, the wet component 26 being forced by the plunger 50 causes the seal 140 to burst. The vacuum within the housing 64 draws the wet component 26 into the housing 64 resulting in a partially wet mixture of the dry component 24 and the wet component 26. The continued pushing of the plunger 50 causes the wet component 26 to mix with the dry medicaments 24. The outlet 70, not shown in FIG. 8, of the mixer 22 has an FDA- acceptable seal that bursts, allowing the drug to enter the injection needle 30, as seen in FIG. 2.

[073] The dry medicament component 24 is shown as particles in the channel 74. The dry component 24 is located in the upper two thirds of the channel 74 to ensure that the dry component 24 is properly mixed with the wet component 26 prior to exiting the outlet 70.

[074] The composition of the wet component 26 is dependent on the dry component 24 and the desired output, the combined medicament 28. The wet component 26 for example could be a buffered hydrochloric acid solution, a saline solution, or a sterile water solution. For example, the EpiPen's formulation is not just epinephrine and water but also contains preservatives, salt, and other components that form the approved solution.

[075] Referring to FIG. 9, a schematic of a system 20 with a syringe 40, a mixer 22, and a wet component storage container 160 is shown. In contrast to the previous embodiment where the wet component 26 is mixed with dry component 24 contemporaneously with the injection into the user 32, in this embodiment the wet component 26 is mixed with the dry component 24 and stored in the syringe 40. It is contemplated in most situations that the combined medicament 28 will be stored in the syringe 40 for a matter of minutes, not days, weeks, or months.

[076] The dry component 24 is stored in the mixer 22; as indicated above the dry component 24 is preferably located in the upper two thirds of the channel 74 to ensure that the dry component 24 is properly mixed with the wet component 26 prior to exiting the outlet 70. The wet component 26 is stored in the wet component storage container 160. The syringe 40 is connected at the inlet 68 of the mixer 22. The wet component storage container 160 is connected to the outlet 70 of the mixer 22; the term outlet 70 is used for standardization in description. It is recognized in this embodiment that the flow is from the outlet 70 to the inlet 68. A needle 60 is carried within the wet component storage container 160 to allow the wet component 26 to be drawn throw the mixer 22. As the plunger 50 of the syringe 40 is pulled back, a vacuum is created pulling the wet component 26 from the wet component storage container 160 through the channels 74 of the mixer 22. The wet component 26 mixes with the dry component 24 and the mixed combined medicament 28 is received in the volume 44 of the syringe 40.

[077] It is the intention that shortly after the combined medicament 28 is received by volume 44 of the syringe 40 that the mixer 22 and the wet component storage container 160 are replaced by the injector, the needle 60.

[078] In an example of the embodiment, the syringe 40 is a 1 mL empty syringe body with a syringe fitting such as Luer-Lock fitting or UniVia fitting. The mixer 22 has a housing 64 with microfluidic mixing channels containing 1 mg of dry drug and a compatible syringe fitting. The drug is completely water soluble at concentrations much greater than lmg/mL. The components are connected by their compatible syringe fittings.

[079] The system has a wet component storage container 160 which is a 10 mL vial of water for injection. In this embodiment, a needle 60 is already attached to the mixer 22 and the syringe 40 is used to draw off lmL of liquid from the 10 mL vial, reconstituting the drug into the body, the volume 44, of the syringe 40. [080] The syringe 40 is driven into the patient's body. The plunger 50 is depressed driving the fluid back through the mixer 22 and the needle 60 out the tip of the needle and into the patient, the user 32. The plunger must be completely depressed to ensure that all of the reconstituted dry drug is administered to the patient.

[081] The volume of the mixer 22 needs to be accounted for in the draw. The syringe 40 can have custom markings. The volume of the mixer 22 would depend greatly on the mass of combined medicament being mixed, its solubility, and shear sensitivity.

[082] Referring back to FIG. 1, in certain drugs 28 it may be desired to mix the dry component 24 with the wet component 26 in two steps. In the first step, the dry component 24 is mixed with a wet component 26 which is tailored to better, quicker placement of the dry component 24 into solution, composition. The solution is then mixed with the additional wet component 34 which results in the final combined medicament 28 for the user 32.

[083] The additional wet component 34 can be a liquid such as a pH adjusting solution. The first wet component 26 could be a solution design to quickly enable dissolution of the dry medicament component 24 or provide additional therapeutic valve.

[084] Referring to FIG. 10, the system 20 with a syringe 40, a mixer 22, a wet component storage container 160 is shown. In contrast to the embodiment shown in FIG. 9 where the syringe 40 begins with the volume 44 and the volume 44 increases as the combined medicament 28, the mixture of the dry component 24 and wet component 26, is pulled into syringe 40 and the volume 44 increases, in this embodiment the syringe 40 starts containing the additional wet component 34. [085] Similar to the previous embodiment, the dry component 24 is stored in the mixer 22. The wet component 26 is stored in the wet component storage container 160. The syringe 40 is connected at the inlet 68 of the mixer 22. The wet component storage container 160 is connected to the outlet 70 of the mixer 22; the term outlet 70 is used for standardization in description. A needle 60 is carried within the wet component storage container 160 to allow the wet component 26 to be drawn through the mixer 22. It is recognized in this embodiment the flow is from the outlet 70 to the inlet 68. As the plunger 50 of the syringe 40 is pulled back a vacuum is created pulling the wet component 26 from the wet component storage container 160 through the channels 74 of the mixer 22. The wet component 26 mixes with the dry component 24 and in contrast to the previous embodiment this mixture is mixed with the additional wet component 34 as this mixture 28 is received in the volume 44 of the syringe 40.

[086] It is the intention that shortly after the combined medicament 28 is received by the volume 44 of the syringe 40 that the mixer 22 and the wet component storage container 160 are replaced by the injector, the needle 60.

[087] Referring to FIG. 11, a schematic of another alternative embodiment of a syringe 40, a mixer 22, and a second component storage container 160 is shown. In contrast to FIG. 10 which has the wet component 26 stored in the addition storage container 160 and drawn through the mixer 22 into the syringe 40, in this embodiment, the wet component 26 is located in the syringe 40. Like the previous embodiment, the mixer 22 contains the dry component 24. In contrast to the embodiment in FIG. 10, the storage container 160 contains the second, additional wet component 34. The dry component 24 and the wet component 26 are mixed similar to that shown in FIG.2. The mixed component is deposited into the storage container 160 as the plunger 50 is depressed.

[088] Referring to FIG. 12, a schematic of an alternative embodiment that has a housing

170 for holding the dry medicament 24 is shown. The schematic of the system 20 shows a syringe 40 and the housing 170 with a needle 60. The syringe 40 has a cylindrical tube

42 defining a volume 44. The cylindrical tube 42 of the syringe 40 tapers down to an outlet port 48. The syringe 40 has a plunger 50 with a depressing handle 52, a shaft 54, and a piston 56 for forcing the wet component 26 out of the outlet port 48.

[089] While the syringe 40 is shown separated from the housing 170 in FIG. 12, the syringe 40 and the housing 170 are connected prior to use. The dry medicament 24 is held in the housing 170 which is a single chamber 172.

[090] Referring to FIG. 13, a schematic of alternative embodiment that has a syringe 180 holding both the dry medicament component 24 and the wet component 26 separated by a membrane 182 is shown. As the user pushes the depressing handle 52 of the plunger 50, the piston 56 asserts a pressure on the wet component 26 which causes the membrane 182 to burst. The wet component 26 flows through the dry component 24 which is located in the lower portion of the syringe 180 between the membrane 182, a second membrane 186 at the outlet port 48, and the taper wall 184 of the syringe 180. The continued force of the piston 56 of the plunger 50 causes the second membrane 186 to burst. The wet component 26 places the dry component 24 into solution by the time the dry component 24 flows to the end of the needle 60.

[091] It is recognized that a mixer device with a flow channel could be inserted into the dry medicament component shown portion of the syringe 180. The flow channel could take various forms including those shown in FIGS. 7 A - 7C. The mixer could be vial containing dry medicament component that has an opening at the top and an opening at the bottom where sanitary seals are removed just prior to insertion into the syringe. The syringe could be come in multiple parts as explained below.

[092] Referring to FIG. 14A, a schematic of an alternative system 190 having a dry medicament container 192 connectable to an alternative style syringe 194 is shown. The syringe 194 has a cylindrical tube 42 defining a volume 44. In contrast to the previous embodiment, the syringe 194 does not taper down, but has a coupling ring 198 that has a groove 200, as best seen in FIG. 14B, to receive an annular ring 202 of the dry medicament container 192.

[093] The dry medicament container 192 has a pair of burst membranes 208. The dry medicament container 192 retains the dry medicament 24 interposed between the pair of burst membranes 208.

[094] Prior to use, a sanitary seal 210 is removed from the syringe 194 and the dry medicament container 192. The syringe 194 and the medicament container 192 are coupled together so the annular ring 202 of the dry medicament container 192 is received in the groove 200 of the syringe as seen in FIG. 14A. The needle 60 is placed into a vial, not shown, containing wet component or medicament. The piston 56 of the plunger 50 is pulled upward away from the dry medicament container 192 creating more volume 44 in the cylindrical tube 42. This action causes the burst membranes to burst and the wet component to flow through the dry medicament 24 and place the dry medicament 24 into solution. The syringe 194 can have an internal stop 212 to stop the plunger 50 at a desired location and desired volume 44. When the proper amount of wet component has been drawn into system 190, the needle 60 is removed from the vial, not shown. The system 190 is ready to be used.

[095] The dry medicament container 192 instead of retaining the dry medicament component 24 in an open chamber, could include an insert having a channel, such as a microchannel. While the interface between the dry medicament container 192 and the syringe 194 is shown as an annular ring, it is recognized that other coupling mechanism can be used such as a threaded coupling.

[096] Referring to FIG. 15, a schematic of alternative embodiment system 1500 having a pair of wet component containers 1516a and 1516b that contain a first wet component 1508a and a second wet component 1508b which are mixed together prior to mixing with a dry medicament component. The syringe of the system 1500 has a plunger 1502 with a pair of shafts 1504 that each drive a plunger 1506 in a respective wet component volume. As the respect wet components 1508a and 1508b are pushed through their respective valve 1510a and 1510b, the wet components mix in a wet mixing volume 1512 where a combined wet component is formed.

[097] As the plunger 1502 continues to push, the combined wet component flows through a fluidic channel 1530 of a mixer 1520 that contains the dry medicament component. The combined medicament, which contains the dry medicament within the combined wet component, flows through the needle 1540.

[098] While the two wet component containers 1516a and 1516b are shown the same size, it is recognized that the cross sectional area can be adjusted to tailor the mixing of the two wet components. In certain embodiments the mixer 1520 and needle 1540 component can be separable from the syringe at the syringe output 1514. [099] While the principles of the invention have been described herein, it is to be understood by those skilled in the art that this description is made only by way of example and not as a limitation as to the scope of the invention. Other embodiments are contemplated within the scope of the present invention in addition to the exemplary embodiments shown and described herein. Modifications and substitutions by one of ordinary skill in the art are considered to be within the scope of the present invention.

[100] It is recognized that the syringe 40 can be replaced by an alternative source of fluid and motive force such as a fluid pump.

[101] It is recognized in certain embodiments, the dry medicament is a stable paste form of the drug. The wet component drives the paste into solution.

[102] The chaotic flow drives the dry component 24 into solution prior to leaving the needle 60. It is recognized that in specific embodiments, that it might be desirable and / or acceptable to have dry particles pass through the needle 60 into the body of the user.

[103] It is recognized that the mixer can take various forms. For example in addition to the cylindrical and the planar designs, it also envisioned that a series of constant x-section channels that flow through and around the disk (plane perpendicular to the flow vector of the liquid leaving the syringe) to minimize assemblage length. The mixer body could also be plane parallel with the flow vector of the liquid leaving the syringe.

[104] It is recognized that the complexity of the mixer and the combined medicament would be customized for the application to ensure that there is sufficient mixing.

Claims

CLAIMS What is claimed:

1. A drug delivery system comprising:

a mixer body having a series of walls defining a channel and an interior flow chamber, the mixer body having an inlet and an outlet, the interior flow chamber receiving a dry medicament component.

2. A drug delivery system of claim 1 further comprising a liquid containment

assembly having an interior chamber, the interior chamber including a wet compartment configured to store a wet component, the wet component capable of mixing with the dry medicament component in the mixer body.

3. A drug delivery system of claim 1 further comprising a syringe assembly having an interior chamber, the interior chamber including a wet compartment configured to store a wet component, the wet component capable of mixing with the dry medicament component in the mixer body.

4. A drug delivery system of claim 3 wherein the syringe assembly and the mixer body have a compatible connection.

5. A drug delivery system of claim 4 wherein the dry component is partially soluble in the wet component.

6. A drug delivery system of claim 4 further comprising an injection needle

detachably connected to the outlet portion of the mixer body.

7. A drug delivery system of claim 1 further comprising an injection needle that is integral with the mixer body.

8. A drug delivery system of claim 1 wherein the mixer body is sized to define a hollow volume sized to the dry medicament component received.

9. A drug delivery system of claim 1 wherein the series of walls of the mixer body define a tortious path for carrying the dry medicament component and defining the volume for mixing the wet medicament with the dry medicament.

10. A drug delivery system of claim 8 wherein the series of walls of the mixer body define a flow path that induces chaos in flow for carrying the dry medicament component and defining the volume for mixing the wet component with the dry medicament.

11. A drug delivery system of any prior claim wherein at least one of the dimensions in the channel is less than 2 millimeters.

12. A drug delivery system of any prior claim wherein at least one of the dimensions in the channel is less than 1 millimeters.

13. A drug delivery system of any prior claim wherein the Reynolds number in the mixer during mixing is less than 2300.

14. A drug delivery system of any prior claim wherein the Reynolds number in the mixer during mixing is less than 100.

15. A drug delivery system of any prior claim wherein the Reynolds number in the mixer during mixing is less than 10.

16. A drug delivery system of any prior claim wherein the mixing assembly further includes a plurality of grooves formed therein, wherein said grooves facilitate mixing through chaotic flow when a wet component flows by said grooves.

17. A drug delivery system of any prior claim wherein the mixing assembly further includes a plurality of bends formed therein, wherein said bends facilitate mixing through chaotic flow when a wet component flows through said bends.

18. A drug delivery system of any prior claim wherein the interior flow chamber of the mixer body is kept in vacuum until the mixer body is attached to the liquid- filled syringe; the mixer body having a failure membrane that fails upon the syringe engaging the mixer body.

19. A drug delivery system of any prior claim further comprising the mixer body having a gas vent structure to ensure that gas trapped in the mixer is vented.

20. An injection device containing a pre-loaded charge of medicament for

administering the medicament upon actuation thereof, the device comprising: a syringe assembly having an interior chamber, the interior chamber including a wet compartment configured to store a wet component; and

a mixing assembly detachably connected to the housing assembly, wherein the mixing assembly defines an inlet configured to connect with the syringe assembly, an outlet, and an interior chamber having a volume, wherein a portion of the mixing assembly contains a dry medicament component configured to mix with the wet component as a result of activation of the syringe assembly, the mixing assembly having an injection needle.

21. A method of preparing an injection device comprising the steps of:

inserting a dry medicament component into a portion of a mixer body having an interior flow chamber; and passing a wet component through the interior flow chamber of the mixer body to mix the wet component with the dry medicament component configured to be detachably connected to the interior chamber, wherein the mixing assembly is in fluid communication with the interior chamber upon activation of the device;.

22. A method of preparing an injection device of claim 21 wherein the wet

component is drawn into the syringe through the mixer body forming a combined component.

23. A method of preparing an injection device of claim 22 further comprising an

injection needle integral with the mixer body.

24. A method preparing an injection device of claim 22 wherein the wet component is pushed from the syringe through the mixer body to form a combined medicament.

25. A method of preparing an injection device of claim 22 wherein the syringe

contains the wet component prior to connection to the mixer body, the mixing occurs as the wet component passes through the mixer body to the injection needle for delivery.

21. A drug delivery system comprising:

an injection device having at least two compartments, the at least two compartments each containing a medicament component, the injection device having an actuation device that mixes the medicament components.

22. A drug delivery system of claim 21 wherein one of the medicament components is a dry medicament component and the second component is a wet component, the injection device having a sealing structure interposed between the two compartments and separating the two components wherein the actuation device creates fluid communication and the wet component to flow into the dry medicament component.

23. A drug delivery system of claim 22 wherein the injection device is separable into at least two sections, one of the sections containing the compartment for the wet component, the second section containing the compartment for the dry medicament component; the sections having coupling mechanism for connecting the sections prior to the actuation device creates fluid communication and the wet component to flow into the dry medicament component.

24. A drug delivery system of claim 21 wherein one of the medicament components is a wet component and the second component is a wet component, the injection device having a wet mixing volume where a combined wet component is formed.

25. A drug delivery system of claim 24 further comprising a mixer body having a series of walls defining a channel and an interior flow chamber, the mixer body having an inlet and an outlet, the interior flow chamber receiving a dry medicament component, the mixer having a compatible connection to the injection device and the combined wet component capable of mixing with the dry medicament component in the mixer body.