Ultrasound-assisted reconstitution of lyophilized products

Abstract

An injection device is provided that includes a body defining a first chamber having a solvent and a second chamber having a lyophilized cake of a medicament, the second chamber being in fluid communication with a needle fluid path that is configured to deliver the medicament to a patient's body at a needle tip, a sealing element separating the first chamber from the second chamber, a coupler at least partially disposed about the second chamber, and at least one transducer disposed about the coupler.

Description

ULTRASOUND- ASSISTED RECONSTITUTION OF LYOPHILIZED PRODUCTSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 716,378, filed November 5, 2024, the entire contents of which are incorporated by reference herein.FIELD OF THE INVENTION

[0002] The present disclosure relates generally to syringes and injectors. More specifically, the present disclosure relates to devices and methods for reconstituting drug products.BACKGROUND OF THE INVENTION

[0003] Biological materials such as cells, proteins and vaccines are frequently preserved by lyophilizing aliquots of a liquid composition containing the biological material. The lyophilization process involves freezing a liquid sample which is then subjected to a vacuum so that the ice in the frozen sample directly changes to water vapor or sublimes. After the removal of ice, the sample temperature is gradually increased (while still under vacuum) and water is desorbed from the remaining non-ice phase of the sample.

[0004] Lyophilized cakes of a biological material are prepared by aliquoting into a glass container a desired amount of the biological material, which is typically present in a buffered solution with appropriate stabilizers (i.e., a “formulation”) and then subjecting the glass container containing the biological matenal to steps of cooling, freezing, annealing, primary drying and secondary drying. The glass container containing the dried biological material is typically stored for long periods of time at room temperature or under refrigerated conditions. The dried formulation containing the biological material is typically reconstituted by adding a diluent or liquid, usually water, to the glass container. Glass containers used for lyophilizing biological materials intended for use as therapeutics and vaccines typically have included glass vials and dual chamber injection devices, in which one chamber contains the lyophilized cake and the other chamber contains the reconstituting liquid.

[0005] Reconstitution of high-concentration lyophilized biotherapeutics (e.g., monoclonal antibodies and protein formulations) could be challenging due to long and variable reconstitution times and non-uniform final reconstituted product, which results in limiting the protein concentrations and increasing the injection / fill volume that necessitates the use of multiple vials per dose. Moreover, in some applications, reconstitution requires manually shaking thetherapeutic to mix the lyophilized cake and the diluent until proper reconstitution, which is inconvenient for the user.

[0006] Thus, there exists a need for devices that improve upon and advance the methods of reconstituting drug products, and lyophilized drug products in particular.SUMMARY OF THE INVENTION

[0007] In some examples, an injection device for delivery7of a medicament comprises a body defining a first chamber and a second chamber, the second chamber being in fluid communication with a needle fluid path that is configured to deliver the medicament to a patient’s body at a needle tip, a plunger separating the first chamber from the second chamber, a bypass through which a substance may travel from the first chamber to the second chamber, a coupler at least partially disposed about the second chamber; and at least one transducer disposed about the coupler.

[0008] In some examples, an injection device for delivery of a medicament comprises a body' defining a first chamber having a solvent and a second chamber having a lyophilized cake of the medicament, the second chamber being in fluid communication with a needle fluid path that is configured to deliver the medicament to a patient's body at a needle tip, a sealing element separating the first chamber from the second chamber, a coupler at least partially disposed about the second chamber, and at least one transducer disposed about the coupler.

[0009] In some examples, a method of encouraging reconstitution of a lyophilized medicament in an injection device comprises providing a body defining a first chamber having a solvent and a second chamber having a lyophilized cake of the medicament, the second chamber being in fluid communication with a needle fluid path that is configured to deliver the medicament to a patient’s body at a needle tip, providing an ultrasound module having a coupler at least partially disposed about the second chamber, and at least one transducer disposed about the coupler, and generating ultrasound waves from the at least one transducer through the coupler toward the second chamber.BRIEF DESCRIPTION OF THE DRAWINGS

[0010] Various embodiments of the presently disclosed syringes are disclosed herein with reference to the drawings, wherein:

[0011] FIG. 1 is a schematic front view of a dual-chambered syringe.

[0012] FIGS. 2A-B are schematic front views of a dual-chambered syringe having an ultrasound module.

[0013] FIGS. 3A-C are schematic front view of several variations of a prefilled syringe having ultrasound modules.

[0014] FIG. 4 is a schematic front view of a multi -cartridge injection system having an ultrasound-module.

[0015] Various embodiments are described below with reference to the appended drawings. It is to be appreciated that these drawings depict only some embodiments of the disclosure and are therefore not to be considered limiting of its scope.DETAILED DESCRIPTION OF THE INVENTION

[0016] Despite the various improvements that have been made to injectors and syringes, conventional methods suffer from some shortcomings as discussed above. Therefore, there is a need for further improvements to the devices and methods used to reconstitute drug products. Among other advantages, the present disclosure may address one or more of these needs.

[0017] As used herein, the term ‘'proximal,” when used in connection with a component of a syringe or injector, refers to the end of the component closest to the user’s hands when holding the device; whereas the term “distal,” when used in connection with a component of a syringe or injector, refers to the end of the component closest to the needle insertion site during use.

[0018] Likewise, the terms “trailing” and “leading” are to be taken as relative to the operator's fingers (e.g., physician) of the syringe or injector. “Trailing” is to be understood as relatively close to the operator’s fingers, and “leading” is to be understood as relatively farther away from the operator’s fingers.

[0019] As seen in FIG. 1, a syringe 100 (a hypodermic syringe in this specific embodiment) may have a generally tubular, cylindrical body 101 typically made of glass and centered on an axis A, and that extends from proximal end 102 to distal end 104. A pressable injection cap 105 may be disposed adjacent proximal end 102. Body 101 may house a proximal plunger 107 and a distal plunger 109. A first chamber 110 may be defined between proximal plunger 107 and distal plunger 109, and a diluent or solvent may be disposed within first chamber 110. A second chamber 120 may be separated from the first chamber 110 with a sealing element. For example, second chamber 120 may be defined betw een distal plunger 109 and nozzle 125 at the distal end 104, and the second chamber 120 may house or receive a lyophilized cake. In some examples, nozzle 125 may be configured to provide delivery of a medicament (e.g., via a needle assembly).

[0020] The purpose of the dual-chambered configuration is to house a lyophilized substance (solute) in one chamber (e.g., second chamber 120) and a solvent in the other chamber (e.g., first chamber 110). In this example, body 101 defines a chamber bypass 115 by which a substance26027 from first chamber 110 may pass to second chamber 120. Syringe 100 utilizes a push action to actuate proximal plunger 107 and / or distal plunger 109 to a position where the solvent passes from one chamber to the other (e.g., via chamber bypass 115), where it is mixed with the lyophilized product in the second chamber. It will be understood that variations on the dualchambered syringe are possible. For example, elements such as the plungers and / or injection caps 105 may be twisted or otherwise actuated to allow the solvent to pass to the lyophilized product and allow for reconstitution, and the chamber bypass 115 may include outwardly defined elements as shown, or other internal channels or pathways by which the solvent from the first chamber 110 is allowed into the second chamber 120 during use. Examples of such syringes include RE34,845 to Vetter et al. and U.S. Patent No. 10,926,036 to Shluzas et al., the contents of which are hereby incorporated by reference as if fully set forth herein. In any case, after the solvent is introduced into the second chamber 120, the user may shake the auto-injector side-to- side to ensure sufficient mixing of the lyophilized cake with the solvent to form a monodose. Once thoroughly mixed, the product may be delivered via a needle at an injection site.

[0021] To improve reconstitution and delivery of highly concentrated lyophilized formulations (e.g., reduce reconstitution time and / or ensure consistency), an ultrasound-mediated delivery system 300A may be used. As seen in FIG. 2A, a syringe 200 (a hypodermic syringe in this specific embodiment) may have a generally tubular, cylindrical body 201 that extends from proximal end 202 to distal end 204. A pressable injection cap 205 may be disposed adjacent proximal end 202. Body 201 may house a proximal plunger 207 and a distal plunger 209. A first chamber 210 may be defined between proximal plunger 207 and distal plunger 209, and a diluent or solvent D " may be disposed within first chamber 210. A second chamber 220 may be defined between distal plunger 209 and nozzle 225 at the distal end 204, and the second chamber 220 may house or receive a lyophilized cake “L”. In some examples, lyophilized cake ‘’L” is initially disposed at the top of the second chamber 220 adjacent distal plunger 209. As previously discussed, nozzle 225 may be configured to provide delivery of a medicament (e.g., via a needle assembly), and a chamber bypass 215 may be defined by which solvent from first chamber 210 may pass to mix with lyophilized cake “L” in second chamber 220 when injection cap 205 is depressed (FIG. 2B). As shown, syringe 200 utilizes a push action to actuate proximal plunger 207 and / or distal plunger 209 to a position where the diluent or solvent “D"’ passes from one chamber to the other (e.g., via chamber bypass 215 through path Pl), where it is mixed with the lyophilized product in the second chamber.

[0022] In this example, an ultrasound module 300 (shown in Figs. 2A and 2B as 300A) is disposed adjacent at or near second chamber 220 and aids in reconstituting lyophilized product26027 when the solvent “D” (shown in Figs. 2A and 2B as D) is added to lyophilized cake “L”. In some examples, ultrasound module 300 may be separably formed and coupleable to syringe 200. For example, ultrasound module 300 may be in the form of an accessory or add-on to an injection device (e.g., an autoinjector) having its own housing and subassembly, and a prefdled syringe 200 may be insertable into the ultrasound module 300 housing. Alternatively, ultrasound module 300 may be integrally formed with a syringe or injector. In some examples, an injector may be in the form of a miniaturized hand-held, portable, battery-operated, reusable, and low-cost ultrasound-assisted injection device similar to an ultrasound-based toothbrush device and sharing many of the same functional components.

[0023] As shown in Figs. 2A and 2B, ultrasound module 300A generally includes one or more transducers 310 and an optional coupler 320. Transducer 310 may be a single, cylindrical piezoelectric transducer that generates ultrasound waves that are directed radially inward toward second chamber 220. In this example, transducer 310 is configured as a collar that fits over and at least partially (or fully covers) second chamber 220 and directs ultrasonic waves toward the lyophilized product. The generated ultrasound waves may be applied to second chamber 220 to induce particle mixing and reconstitution. In some examples, a cylindrical piezoelectric transducer 310 may have a fundamental frequency ranging from 10 KHz - 100 MHz (e.g., from 20 KHz - 90 KHz. from 30KHz - 80 KHz, from 40 KHz - 70 KHz, or from 50 KHz - 60 KHz), and may generate ultrasound waves with an amplitude of 110± 50 mV peak-to-peak (e.g., 60 mV, 70 mV, 80 mV, 90 mV, 100 mV, 110 mV, 120 mV, 130 mV, 140 mV, 150 mV, or 160 mV) and a frequency modulation range of 15 ± 10 Hz (e.g., 65 kHz center). Disposed between transducer 310 and second chamber 220 is an optional coupler 320. In some examples, coupler 320 is a polyvinyl alcohol (PVA) hydrogel coupler that acts as an ultrasound gel to replace air and facilitate ultrasound w ave propagation. It will be understood that other materials may be used for coupler 320 including glycerol, ethylene glycol, mineral oils, and other polymer-based hydrogels as well as elastomers, thermoplastics, and thermosets and the like. Coupler 320 may be disposed in, or fill, all or most areas between second chamber 220 and transducer 310.Ultrasound module 300A may include a battery or other power source to power transducer 310, and may also include a microprocessor (e.g., a function generator). In some examples, the ultrasound module 300A may generate standing w aves within the cavity of the cylindrical transducer immersed in a scattering medium. Specifically, waves from opposing sides of the cylindrical transducer 310 may undergo constructive and / or destructive interference. Frequency modulation- within a given envelope covering a range of 15 ± 10 Hz expanding beyond thecenter frequency of 65 kHz. may also be employed to effectively scan the pressure nodes within the inner cavity of the cylindrical transducer to promote reconstitution.

[0024] As previously noted, ultrasound module 300A may aid in reconstitution of lyophilized products ranging from small molecule formulations to large molecules proteins and biologies including monoclonal antibody drugs and antibody drug conjugates. In addition, the principles applied herein may be used to mix any two medicaments (e g., two liquid formulations to be mixed). As user herein, the term “medicament” is used broadly to include any formulation, suspension, medicine, substance, therapeutic or combinations of such, to be delivered to a patient with a syringe.

[0025] In use, the ultrasound module 300A may be disposed over portions of a syringe (e.g., second chamber 220) with coupler 320 filling the space between the syringe and transducer 310. Transducer 310 may be powered via a battery or other power source. During injection, the transducer 310 may direct ultrasound waves toward second chamber 220 where the lyophilized cake “L” is being mixed with solvent “D” In some examples, the transducer 310 generates ultrasound waves toward second chamber 220 before, during, and after the user begins to dispense the medicament. For example, ultrasound module 300A may be configured so that the transducer is powered on when the user touches or presses on injection cap 205. The ultrasound waves may be generated for a portion of the injection or through the entire injection time. For example, ultrasound waves may be generated until the contents of the syringe are emptied or delivered, thereby reducing the reconstitution time, and / or enhancing the quality or uniformity of the final reconstituted products.

[0026] Variations on these principles are possible. For example, Figs. 2A-2B illustrate a system in which transducer 310 and coupler 320 are disposed over only a small portion of second chamber 220 adjacent the distal end of the chamber. In that example, the transducer and coupler are disposed over less than half of the length of the second chamber, leaving most of the second chamber visible from the outside for the user to see the reconstitution. Fig. 3A illustrates a variation in which the ultrasound module 300B comprising the transducer 310 and coupler 320 cover more than half of the length of second chamber 220. Fig. 3B illustrates a variation in which the ultrasound module 300C comprising the transducer 310 and coupler 320 cover all or almost all of second chamber 220. Fig. 3C illustrates a variation in which the ultrasound module 300D comprising the transducer 310 and coupler 320 cover any combination, or all of first chamber 210, bypass 215 and second chamber 220. The transducers and couplers may be substantially cylindrical as previously described, or may take the form of other shapes. Additionally, multipletransducers and / or couplers may be positioned radially about the outer circumference of the syringe adjacent one or more of the chambers to make up the ultrasound module.

[0027] The principles of the present disclosure may be useful for other needle-based syringes or injector systems for uses other than lyophilized products. For example, turning to FIG. 4, an exemplary multi-cartridge injector 400 includes a pair of barrels or cartridges. Injector 400 is configured to be generally symmetrical about a longitudinal central axis ‘"Y” Injector 400 generally extends between a proximal end 402 and a distal end 404. Moving from the proximal end to the distal end, injector 400 includes a plunger 410 that is formed of a main brace 411, and a pair of stems 412a and 412b that terminate in couplers for mating with stoppers 430a and 430b.

[0028] Injector 400 further includes a containment unit 440 that includes a pair of barrels 441a and 441b. In some examples, each of barrels 441a and 441b is substantially cylindrically shaped and each includes a sidewall 444a and 444b and a respective lumen 442a and 442b for accepting at least a portion of stems 412a and 412b and stoppers 430a and 430b. Barrels 441a and 441b may terminate in openings 446a and 446b close to the distal end 404. In some examples, the two barrels 441a and 441b are disposed side-by-side and may be joined at a common wall 448.Optionally, each of barrels 441a and 441b may include a respective rectangular window 449a and 449b, and the window may be sized to receive the vials or container closure systems. In other examples, the vials or container closure systems are loaded from the bottom of a barrel and the windows 449a and 449b are transparent or open cutouts used as a visualization tool to see inside the containment unit and confirm proper delivery of the medicament from the vials.

[0029] The containment unit may be used to hold the two separate container closure sy stems during packaging and shipping. Specifically, each barrel 441a and 441b may define a respective reservoir that holds a medicament, drug, saline, or other substance for injecting into a patient’s body. In some examples, reservoirs are sized to accept a container closure system, vial or cartridge and these terms are used interchangeably throughout the disclosure. Vaccines and biologies may be stored in vials made of borosilicate glass, known for its chemical stability- and its ability to withstand long refrigeration and impact during transportation.

[0030] A Y-shaped conduit 450 may be used with injector 400. Y-shaped conduit 450 may include a pair of branches 452, each having a piercing tip 451, the branches meeting and joining at a common hollow shaft 454. Y-shaped conduit 450 may define a continuous lumen from each of the branches 452 down to the common hollow shaft 454. and the tips of the two branches 452 may be sized and spaced so that they pierce a container within each of the barrels 441a and 441b.

[0031] Y-shaped conduit 450 may be partially disposed within each of barrels 441a and 441b, and common hollow shaft 454 may be at least partially disposed within cap 460. Cap 460 may befunnel-shaped at a first end 462 and have a hub 433 (in this specific embodiment which is a plastic hub) having a luer-fitting configured and arranged to mate with a disposable probe needle 434 (e.g., 18-gauge disposable needle). Thus, a standard off-the-shelf luer-lock probe needle may engage with the luer-lock threading of the cap 460 to create one continuous passage from the probe needle 434 to the piercing tips 451. This continuous passage may direct fluid from the cartridges through the engagement of the containment unit 440 and the probe needle 434 into the patient with the application of pressure to the plunger rod 410. In one embodiment, cap 460 is engaged by a press-fit or similar mechanism to the containment unit. In this example, an ultrasound module 300 may be disposed about the hub 433 and may generally include a transducer 310 and a coupler 320 as previously described.

[0032] The dual-cartridge combination product injector 400 allows for the simultaneous delivery of the contents of two separate container closure systems into one injection site. Injector 400 may provide a simple, easy-to-use method to accurately deliver two drug product solutions from separate container closure systems or vials with an easy to recognize design. One advantage of these configurations is that they provide an easier way to administer medication. Specifically, injector 400 requires less steps and needle sticks for patients to self-administer two medicines at home, reduces environmental waste, increases stability of the drug formulation and shelf life individually, reduces impact from complicated mixing interactions and medication errors, and improves access to underserved markets. In this example, an ultrasound module 300 may be disposed over common hollow shaft 454 and / or hub 433 to assist in mixing the drug products from barrels 441a and 441b.

[0033] To use the system, a clinician, patient or user may assemble the components as described above, or the components may be pre-assembled by a manufacturer or care provider. Two separate vials or containers may be inserted into barrels 441a and 441b with a pierceable member of each facing branches 452 of Y-shaped conduit 450. In some examples, Y-shaped conduit 450 includes a hollow set of tubing (e g., a polymer tubing) or stainless-steel components. The piercing tips 451 of branches 452 may penetrate the containers to provide fluid communication betw een the probe needle 434 and the interior of the containers. To deliver the drug product into the patient, the user may simply grasp the flange 420 with, for example, their index and middle fingers, and press against the main brace 411 of plunger 410 with their thumb so that the plunger rod pushes the stoppers 430a and 430b and translates them through the barrels 441a and 441b, causing the contents of the containers to flow through the Y-shaped conduit 450 and the probe needle 434 into the patient’s body. Simultaneously, the ultrasound module 30026027 may be powered to mix the contents of the two barrels 441a and 441b prior to delivery to the patient through hub 433 and needle 434.

[0034] In some examples, an injection device may include a body defining a first chamber and a second chamber, the second chamber being in fluid communication with a needle fluid path that is configured to deliver the medicament to a patient’s body at a needle tip, a plunger separating the first chamber from the second chamber, a bypass through which a substance may travel from the first chamber to the second chamber, a coupler at least partially disposed about the second chamber; and at least one transducer disposed about the coupler.

[0035] The features or aspects of the disclosure may be combinable. In some examples, any of the features recited in the claims are combinable with others. For example. The injection device may have a coupler that comprises a gel; and / or a polyvinyl alcohol hydrogel; and / or the device may have at least one transducer, which could be a single transducer and / or a cylindrical transducer disposed over a majority of the second chamber; and / or the at least one transducer may be a piezoelectric transducer; and / or the transducer may be configured to generate ultrasonic waves at the second chamber; and / or has a fundamental frequency ranging from 10 kHz to 100 MHz; and / or the transducer may also be configured to generate ultrasound waves with an amplitude of 110±50 mV peak-to-peak and / or a frequency modulation range of 15±10 Hz; and / or the injection device may include a power source in electrical communication with the at least one transducer; and / or the device may include a solvent in the first chamber and / or a lyophilized cake in the second chamber.

[0036] In some examples, an injection device includes a body defining a first chamber having a solvent and a second chamber having a lyophilized cake, the second chamber being in fluid communication with a needle fluid path that is configured to deliver the medicament to a patient’s body at a needle tip, a sealing element separating the first chamber from the second chamber, a coupler at least partially disposed about the second chamber, and at least one transducer disposed about the coupler.

[0037] In some examples, any of the features recited in the claims are combinable with others. For example, the coupler may include a polyvinyl alcohol hydrogel; and / or the at least one transducer comprises a cylindrical transducer disposer over the coupler and the injection device; and / or the at least one transducer comprises a piezoelectric transducer; and / or the at least one transducer has a fundamental frequency ranging from 10 KHz - 100 MHz.

[0038] In some examples, a method of encouraging reconstitution of a lyophilized medicament in an injection device includes providing a body defining a first chamber having a solvent and a second chamber having a lyophilized cake of the medicament, the second chamber being in fluid26027 communication with a needle fluid path that is configured to deliver the medicament to a patient’s body at a needle tip; providing an ultrasound module having a coupler at least partially disposed about the second chamber, and at least one transducer disposed about the coupler; and generating ultrasound waves from the at least one transducer through the coupler toward the second chamber.

[0039] The method may include the step of delivering the solvent from the first chamber to the second chamber to be mixed with the lyophilized cake; and / or generating ultrasound waves comprises focusing ultrasonic energy onto the second chamber; and / or the step of delivering the medicament after the solvent and the lyophilized cake are mixed under ultrasonic energy.

[0040] It is to be understood that the embodiments described herein are merely illustrative of the principles and applications of the present disclosure. For example, the shape and type of transducer(s) used may be varied as well as the type of coupler. Moreover, certain steps are optional, and the disclosure contemplates various configurations and combinations of the steps disclosed herein. It is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present disclosure as defined by the appended claims.

[0041] It will be appreciated that the various dependent claims and the features set forth therein can be combined in different ways than presented in the initial claims. It will also be appreciated that the features described in connection with individual embodiments may be shared with others of the described embodiments.

Claims

CLAIMS1. An injection device for delivery of a medicament comprising: a body defining a first chamber and a second chamber, the second chamber being in fluid communication with a needle fluid path that is configured to deliver the medicament to a patient’s body at a needle tip; a plunger separating the first chamber from the second chamber; a bypass through which a substance may travel from the first chamber to the second chamber; a coupler at least partially disposed about the second chamber; and at least one transducer disposed about the coupler.

2. The injection device of claim 1, wherein the coupler comprises a gel.

3. The injection device of any one of claims 1-2, wherein the coupler comprises a polyvinyl alcohol hydrogel.

4. The injection device of any one of claims 1-3, wherein the at least one transducer comprises a single transducer.

5. The injection device of any one of claims 1-4, wherein the at least one transducer comprises a cylindrical transducer disposer over a majority of the second chamber.

6. The injection device of any one of claims 1-5, wherein the at least one transducer comprises a piezoelectric transducer.

7. The injection device of any one of claims 1-6, wherein the at least one transducer is configured to generate ultrasonic waves at the second chamber.

8. The injection device of any one of claims 1-7, wherein the at least one transducer has a fundamental frequency ranging from 10 KHz - 100 MHz.

9. The injection device of any one of claims 1-8, wherein the at least one transducer is configured to generate ultrasound waves with an amplitude of 110± 50 mV peak-to-peak and a frequency modulation range of 15 ± 10 Hz.

10. The injection device of any one of claims 1-9, further comprising a power source in electrical communication with the at least one transducer.

11. The injection device of any one of claims 1-10, wherein the injection device comprises a solvent in the first chamber and a lyophilized cake in the second chamber.

12. An injection device for delivery of a medicament comprising: a body defining a first chamber having a solvent and a second chamber having a lyophilized cake, the second chamber being in fluid communication with a needle fluid path that is configured to deliver the medicament to a patient’s body at a needle tip; a sealing element separating the first chamber from the second chamber; a coupler at least partially disposed about the second chamber; and at least one transducer disposed about the coupler.

13. The injection device of claim 12, wherein the coupler comprises a polyvinyl alcohol hydrogel.

14. The injection device of any one of claims 12-13, wherein the at least one transducer comprises a cylindrical transducer disposer over the coupler and the injection device.

15. The injection device of any one of claims 12-14, wherein the at least one transducer comprises a piezoelectric transducer.

16. The injection device of any one of claims 12-15, wherein the at least one transducer has a fundamental frequency ranging from 10 KHz - 100 MHz.

17. Amethod of encouraging reconstitution of a lyophilized medicament in an injection device comprising:providing a body defining a first chamber having a solvent and a second chamber having a lyophilized cake of the medicament, the second chamber being in fluid communication with a needle fluid path that is configured to deliver the medicament to a patient’s body at a needle tip; providing an ultrasound module having a coupler at least partially disposed about the second chamber, and at least one transducer disposed about the coupler; and generating ultrasound waves from the at least one transducer through the coupler toward the second chamber.

18. The method of claim 17, further comprising the step of delivering the solvent from the first chamber to the second chamber to be mixed with the lyophilized cake.

19. The method of any one of claims 17-18, wherein generating ultrasound waves comprises focusing ultrasonic energy onto the second chamber.

20. The method of any one of claims 17-19, further comprising the step of delivering the medicament after the solvent and the lyophilized cake are mixed under ultrasonic energy.

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