Ultrasound-mediated delivery of suspensions

Abstract

The present disclosure provides, in particular embodiments, an injection device including a reservoir for containing a medicament, a needle hub in communication with the reservoir, wherein the needle hub defines a target mixing zone, a needle having a needle fluid path in communication with the needle hub and configured to deliver the medicament to a patient's body at a needle tip, a coupler at least partially disposed about the needle hub, and at least one transducer disposed about the coupler.

Description

ULTRASOUND-MEDIATED DELIVERY OF SUSPENSIONSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 716,393, 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 preventing clogging of needle-based syringes and injectors.BACKGROUND OF THE INVENTION

[0003] Certain high concentration drug products utilize staked-in-needle or Luer Lok prefilled syringe delivery devices, which may be prone to needle clogging. Certain products, like suspensions, are prone to needle clogging due to, for example, particle agglomeration within parts of the syringe. Additionally, once drug product has entered the needle fluid path there is potential for water vapor transmission to occur through the prefilled syringe rigid needle shield, which leads to drying of the drug product within the needle fluid path and causes the drug product to crystalize. As the drug product crystalizes, it forms solid-like particles which can result in needle clogging or partial occlusions.

[0004] When the needle clogging phenomenon occurs, it prevents the end user (e.g., healthcare professional, patient, etc.) from being able to administer the therapeutic dose. Inability to administer therapeutic dosage or a missed dose can have a multitude of negative implications including customer or patient annoyance, impact to therapeutic treatment plans, and increased cost of treatment. Depending on the specific drug product being administered the variety and extent of these implications may differ. Because of this, particle jamming and needle clogging represent a major challenge in the delivery' of suspension formulations.

[0005] Thus, there exists a need for devices that improve upon and advance the methods of safely using injectors and syringes, such as prefilled syringes, and to reduce the possibility of clogging during use.SUMMARY OF THE INVENTION

[0006] In some examples, an injection device includes a reservoir for containing a medicament, a needle hub in communication with the reservoir, the needle hub defining a target mixing zone, a needle having a needle fluid path in communication with the needle hub and configured to deliver the medicament to a patient’s body at a needle tip. a coupler at least partially disposed about the needle hub, and at least one transducer disposed about the coupler.

[0007] In some examples, an ultrasound module for an injection device includes a coupler engageable to the injection device; and at least one transducer disposed about the coupler.

[0008] In some examples, a method of preventing clogging of an injection device includes providing a reservoir for containing a medicament, a needle hub in communication with the reservoir, the needle hub defining a target mixing zone, and a needle having a needle fluid path in communication with the needle hub and configured to deliver the medicament to a patient's body at a needle tip, providing a coupler at least partially disposed about the needle hub, and at least one transducer disposed about the coupler, and generating ultrasound waves from the at least one transducer through the coupler.BRIEF DESCRIPTION OF THE DRAWINGS

[0009] Various embodiments of the presently disclosed syringes are disclosed herein with reference to the drawings, wherein:

[0010] FIG. 1 is a schematic front view of a prefilled syringe.

[0011] FIGS. 2A-2B are magnified photographs showing blockages of dried formulation within a needle tip.

[0012] FIGS. 3A-3B are a schematic front view of a prefilled syringe having an ultrasoundmodule, and magnified views of certain parts of the prefilled syringe and delivery system.

[0013] FIG. 3C is a schematic showing ultrasound waves generated by a cylindrical transducer.

[0014] FIG. 4 and FIG. 5 are charts showing the effects of ultrasound-mediated inj ectability of suspensions.

[0015] FIG. 6 and FIG. 7 are charts of additional experiments showing the effects of ultrasound-mediated injectability of suspensions.

[0016] FIG. 8 is a schematic front view of a multi-cartridge injection system having an ultrasound-module.

[0017] 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

[0018] Despite the various improvements that have been made to injectors and syringes, such as prefilled 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 deliver medication and prevent clogging. Among other advantages, the present disclosure may address one or more of these needs.

[0019] 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.

[0020] 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.

[0021] Reference is now made to FIG. 1, which shows an exemplary syringe 100 (in this specific embodiment, a prefilled syringe) contained within a needle safety device. It will be understood that though a needle within a safety device is shown, the disclosure is not thus limited. For example, though a prefilled syringe with a staked needle is shown, it will be understood that the principles disclosed herein are equally applicable to other types of injectors (e.g., syringes with removable needles, auto-injectors, or on-body (wearable) injectors having needles, etc.). Syringe 100 generally comprises two main portions, a plunger rod assembly 110 and a barrel 120. Plunger rod assembly 110 generally extends between a proximal end 112 and a distal end 114, and generally comprises an elongated piston 115 and a housing 116 extending between a plunger flange 117 and a stopper 130.

[0022] A cylindrical barrel 120 extends between proximal end 122 and distal end 124 and comprises a body 125 defining a lumen 126 for accepting a portion of plunger rod assembly 110. Body 125 further comprises a barrel flange 127 adjacent proximal end 122 and defines a reservoir “R” that holds a medicament, drug, saline, or other substance for injecting into a patient’s body. An internally threaded stopper 130 is disposed inside lumen 126 of body 125. In one embodiment, stopper 130 is made of an elastomeric material such as natural rubber, synthetic rubber, thermoplastic elastomers, or combinations thereof, and comprises an opening to receive and mate with a portion of plunger rod assembly 110 by advancing a portion of the plunger rod assembly inside the barrel lumen 126 and rotating at least one of coupler 119 and stopper 130 relative to the other. At distal end 124, a needle 134 is coupled to a hub 133 (in this specificembodiment which is a plastic hub), which in turn is coupled to the body 125 of barrel 120. In this example, a cap 135 is disposed over needle 134. Once cap 135 is removed, the user may pierce the patient’s skin with the needle, then push on plunger flange 117 to drive the plunger to deliver a medicament through needle 134 into the patient's body.

[0023] Clogging may occur at various portions along the length of the syringe including clogging sites Cl, C2 as shown in FIG. 1. For example, clogging may also occur at or near hub 133 (e.g., at the proximal end of needle 134) adjacent clogging site Cl when particles accumulate locally within the hub. Needle clogging results in stopping the flow through the needle, increasing hydrodynamic pressure in the syringe that is often associated with leakage at the luer lock connection or rubber stopper interface with the syringe wall, which are signatures of injection failure and poses a major risk of compromising dose accuracy and patient safety.

[0024] FIG. 2A-2B are magnified photographs show ing a needle 134 and blockages of dried formulation 180 at the needle tip (e.g.. clogging site C2) within needle fluid path 139. These blockage or partial occlusions may form when the drug product crystalizes from exposure to, for example, water vapor to create solid-like particles which can result in needle clogging. The occlusions may require increased effort to force the drug product through a partial occlusion, or may prevent the injection of the drug product entirely. The present disclosure may address one or both of these issues.

[0025] FIGS. 3A-3B illustrate one potential solution to this problem, which includes an ultrasound module 300 that forms part of an ultrasound-mediated delivery system. In FIG. 3A, a syringe 100 may include the same elements previously described (e.g., plunger rod assembly 110, barrel 120, elongated piston 115, housing 116, and stopper 130, etc.). It will be understood that the syringe 100 may include a staked needle, a prefilled syringe or a luer-lock syringe with attached Luer needle. In this example, an ultrasound module 300 is disposed adjacent, at, or near hub 133 (e.g., at the proximal end of needle 134) where it can reduce the incidence of clogging within the hub 133 and / or needle 134. In some examples, ultrasound module 300 may be separably formed and coupleable to the syringe 100. 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 syringe 100 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.26030

[0026] Turning to FIG. 3B, details of ultrasound module 300 will now be discussed. As shown in FIG. 3B, ultrasound module 300 generally includes one or more transducers 310 and a coupler 320. Transducer 310 may be a single, cylindrical piezoelectric transducer that generates ultrasound waves that are directed radially inward toward hub 133 (in some embodiments hub 133 is a plastic hub). In this example, transducer 310 is configured as a collar that fits over and at least partially (or fully) covers hub 133 and directs ultrasound waves toward target mixing zone 137. The generated ultrasound waves may be applied to the hub 133 region or needle 134, and specifically target mixing zone 137, to induce particle mixing and mitigate the risk of clogging within the hub. 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). Optionally, disposed between transducer 310 and hub 133 is a coupler 320. In some examples, coupler 320 acts as an ultrasound gel to replace air and facilitate ultrasound wave propagation. In some examples, coupler 320 is a polyvinyl alcohol (PVA) hydrogel coupler that acts as an ultrasound gel to replace air and facilitate ultrasound wave 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, or even piezo material such as SM410, and the like. Coupler 320 may be disposed in, or fill, all or most areas between hub 133 and transducer 310.

[0027] Ultrasound module 300 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 300 may generate standing ultrasound waves within the cavity of the cylindrical transducer immersed in a scattering medium. Specifically, ultrasound waves 330 from opposing sides of the cylindrical transducer 310 may undergo constructive and / or destructive interference as shown in FIG. 3C. Frequency modulation within a given envelope covering a range of 15 ± 10 Hz expanding beyond the center frequency of 65 kHz), may also be added to effectively scan the pressure nodes within the inner cavity of the cylindrical transducer to promote mixing of the liquid phase and the suspended solid particle phase. Ultrasound module 300 may also include a spring to promote a smooth injection of pharmaceutical ingredients. In some examples, the spring may comprise stainless steel or other high elastic modulus (e.g., largerthan 5()GPa) metals, representing spring-driven plunger rods found in commercial autoinjector devices.

[0028] As previously noted, ultrasound module 300 may prevent particle agglomeration and promote suspension mixing, thus facilitating injectability of suspensions with a lower injection force without needle clogging. This may be especially true for suspension formulations, which contain a carrier fluid and secondary solid phase particles. Examples of such suspensions include crystalline formulations, amorphous formulations, and other precipitation-based or dispersionbased pharmaceutical formulations containing solid particles in a vehicle. The formulations may also include formulations that tend to sediment or form “cake” over time (e.g., aluminum-based conjugates). As used 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.

[0029] In use, the ultrasound module 300 may be disposed over portions of a syringe (e.g., hub 133) 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 330 at target mixing zone 137 within hub 133. In some examples, the transducer 310 may generate ultrasound waves 330 toward target mixing zone 137 before, during, and / or after the user begins to dispense the medicament (e.g., by pressing onto plunger flange 117). For example, the ultrasound module 300 may be configured so that the transducer 310 is pow ered on w hen the user touches or presses onto plunger flange 117. The ultrasound module 300 may be configured so that the transducer 310 is powered on when the user touches or presses a separate power switch. The ultrasound waves 330 may be generated for a portion of the injection or through the entire injection period. For example, ultrasound waves 330 may be generated until the contents of the syringe are emptied or delivered, thereby reducing or eliminating the risk of clogging at hub 133. In some examples, the transducer 310 may generate ultrasound waves 330 toward target mixing zone 137 before the user begins to dispense the medicament (e.g., by pressing onto plunger flange 117). In some examples, the transducer 310 may generate ultrasound waves 330 toward target mixing zone 137 during the time the user begins to dispense the medicament (e.g., by pressing onto plunger flange 117). In some examples, the transducer 310 may generate ultrasound waves 330 tow ard target mixing zone 137 before, after or while the user begins to dispense the medicament (e.g., by pressing onto plunger flange 117).

[0030] FIGS. 4-7 are exemplary charts showing the effects of ultrasound-mediated injeclability of suspensions using the ultrasound module 300 described above. As will be appreciated,ultrasound waves, administered below the threshold for heat generation or mechanical damage may enable the delivery of localized acoustic energy to target media. Acoustic pressure waves deposit radiation force to target regions via mechanical coupling, providing opportunities to prevent particle agglomeration and / or separate the aggregated particles. The experiments below demonstrate the positive impact of ultrasound waves on improved injectability of suspensions using a needle and syringe system. The results of these experiments demonstrate that pressure waves, induced by ultrasound, can sen e as an effective non-contact mixing tool to provide particle agitation and prevent hub or needle clogging.Experiment 1

[0031] In FIG. 4, a first experiment was conducted with a suspension having glass, hollow spheres as the particle material and shape in a water carrier fluid. The particle density was 1.4 g / cm3and the particle size was D50: 10 pm (2-20 pm). Particle volume was 20 vol%, the needle / syringe used was a BD 25G Y 1 mL plastic Luer-Lok™ and the injection rate was 3 mL / min for 20 seconds. Ten runs are shown on the left and each run measures the plunger force (in New tons) over an injection time of approximately 20 seconds. With the ultrasound module 300 turned off, large spikes in plunger force are shown, including spikes of 5 Newtons, 10 Newtons, 20 Newton, and even up to 40 Newtons in some of the runs. In stark comparison, ten runs are shown on the right with ultrasound module 300 being used to prevent clogging and provide a smooth injection. In the ten runs on the right, all the variables were kept constant with respect to the initial ten runs on the left. In each of the ten runs on the right, the injection force is smooth and does not go above 3-5 Newtons, which illustrates a dramatic reduction in hub and / or needle clogging.Experiment 2

[0032] In FIG. 5, a second experiment was conducted with a suspension having glass, hollow spheres as the particle material and shape in a water carrier fluid. In this experiment, the particle density was 1.4 g / cm3and the particle size was D50: 10 pm (2-20 pm). Particle volume was 10 vol%, the needle / syringe used was a BD 27G ‘A” 1 mL plastic Luer-Lok™ and the injection rate was 3 mL / min for 20 seconds. Similar to Experiment 1, ten runs are shown on the left and each run measures the plunger force (in Newtons) over an injection time of approximately 20 seconds. With the ultrasound module 300 turned off, large spikes in plunger force are shown, including spikes of up to 60 New tons in some of the runs indicating clogging of the syringe. In stark comparison, ten runs are show n on the right with ultrasound module 300 being used to prevent26030 clogging and provide a smooth injection. In each of the ten runs on the right, the injection force is smooth and does not go above 3-5 Newtons which gain illustrates a dramatic reduction in hub and / or needle clogging.Experiment 3

[0033] FIG. 6 is an illustration that summarizes the effects of particle concentration. In this experiment, a fixed needle size of 27G was maintained in two runs, while the volume % of the suspension was varied. As shown in the upper portion, without the use of ultrasound, there was no clogging at 5 vol %, some transitional clogging at 10 vol %, clogging at 20 vol % and extreme clogging at 25 vol %. With the use of ultrasound, and without making any other changes, there was no clogging in 5 vol % or 10 vol % formulations, and only some transitional clogging at 20 vol % and 25 vol % cases. These improvements illustrate that for the same needle, ultrasound- mediated delivery reduces the possibility’ of clogging for certain particle concentrations.Experiment 4

[0034] FIG. 7 is an illustration that summarizes the effects of needle inner diameter (“needle ID"’ in FIG. 7). In this experiment, a fixed 20 vol % particle concentration w as maintained in two runs, while the needle size was varied. As shown in the upper portion, with no ultrasound, there was no clogging at 22G, some transitional clogging at 25G, and clogging at 27G. In contrast, with the use of ultrasound-mediated delivery systems described herein, and without making any other changes, there was no clogging in the 22G and 25G needles, and only some transitional clogging in the 27G needles. These improvements illustrate that for the same particle concentration, ultrasound-mediated delivery allowed for the use of smaller gauge needles, which has tremendous clinical advantages.

[0035] It will be understood that the principles of the present disclosure may be useful for other needle-based syringes or injector systems. For example, turning to FIG. 8, an exemplary multicartridge 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 and430b.

[0036] 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 accepting26030 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 440 and confirm proper delivery of the medicament from the vials.

[0037] The containment unit 440 may be used to hold the two separate container closure systems 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.

[0038] 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 tw o branches 452 may be sized and spaced so that they pierce a container within each of the barrels 441a and 441b.

[0039] 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 a cap 460. Cap 460 may be funnel-shaped at a first end 462 and have a hub 433 (in this specific embodiment, which is plastic) having a luer-fitting configured and arranged to mate with a disposable probe needle (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 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 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 440. 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 about hub 433 as previously described.

[0040] The specific dual-cartridge combination product injector 400 illustrated may allow for the simultaneous delivery7of the contents of tw o separate container closure systems into one26030 injection site. Injector 400 may provide a simple, easy-to-use method to accurately delivery two or more 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 w ay to administer medication. Specifically, injector 400 requires less steps and needle sticks for patients to self-administer two or more 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.

[0041] 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. In this specific embodiment, 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 hollow7set 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 between 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 Y- shaped conduit 450 and the probe needle 434 into the patient’s body.

[0042] In some examples, an injection device includes a reservoir for containing a medicament, a needle hub in communication with the reservoir, the needle hub defining a target mixing zone, a needle having a needle fluid path in communication with the needle hub and configured to deliver the medicament to a patient’s body at a needle tip. a coupler at least partially disposed about the needle hub, and at least one transducer disposed about the coupler.

[0043] Certain features or aspects of the disclosure may be combinable. In some examples, the coupler comprises a gel; and / or the coupler comprises a polyvinyl alcohol hydrogel; and / or the at least one transducer comprises a single ultrasound transducer; and / or the at least one transducer comprises a cylindrical ultrasound transducer disposed over a majority of the needle hub; and / or the at least one transducer comprises a piezoelectric transducer; and / or the at least one transducer is configured to generate ultrasound waves at the target mixing zone; and / or the at least one transducer has a fundamental frequency ranging from 10 KHz - 100 MHz; and / or the at least one transducer is configured to generate ultrasound waves with an amplitude of 1 10± 50 mV peak-to- peak and a frequency modulation range of 15 ± 10 Hz; and / or the device further comprising a26030 power source in electrical communication with the at least one transducer; and / or the injection device comprises a prefilled syringe.

[0044] In some examples, the present disclosure provides an ultrasound module for an injection device, that comprises a coupler engageable to the injection device; and at least one transducer disposed about the coupler. The coupler may comprise 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.

[0045] In some examples, a method of preventing clogging of an injection device includes providing a reservoir for containing a medicament, a needle hub in communication with the reservoir, the needle hub defining a target mixing zone, and a needle having a needle fluid path in communication with the needle hub and configured to deliver the medicament to a patient's body at a needle tip, providing a coupler at least partially disposed about the needle hub, and at least one transducer disposed about the coupler, and generating ultrasound waves from the at least one transducer through the coupler.

[0046] The at least one transducer has a fundamental frequency ranging from 10 KHz - 100 MHz; and / or generating ultrasound waves comprises focusing ultrasonic energy' onto the target mixing zone; and / or the method further includes the step of delivering the medicament through a needle while the at least one transducer generates ultrasonic energy onto the needle hub.

[0047] 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.

[0048] 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 comprising: a reservoir for containing a medicament; a needle hub in communication with the reservoir, the needle hub defining a target mixing zone; a needle having a needle fluid path in communication with the needle hub and configured to deliver the medicament to a patient's body at a needle tip; a coupler at least partially disposed about the needle hub; 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 claim 1, 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 ultrasound transducer.

5. The injection device of any one of claims 1-4, wherein the at least one transducer comprises a cylindrical ultrasound transducer disposed over a majority of the needle hub.

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 ultrasound waves at the target mixing zone.

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 1-7, 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 prefilled syringe.

12. An ultrasound module for an injection device, comprising: a coupler engageable to the injection device: and at least one transducer disposed about the coupler.

13. The ultrasound module of claim 12, wherein the coupler comprises a polyvinyl alcohol hydrogel.

14. The ultrasound module 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 ultrasound module of any one of claims 12-14, wherein the at least one transducer comprises a piezoelectric transducer.

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

17. A method of preventing clogging of an injection device comprising: providing a reservoir for containing a medicament, a needle hub in communication with the reservoir, the needle hub defining a target mixing zone, and a needle having a needle fluid path in communication with the needle hub and configured to deliver the medicament to a patient’s body at a needle tip; providing a coupler at least partially disposed about the needle hub, and at least one transducer disposed about the coupler; and generating ultrasound waves from the at least one transducer through the coupler.

18. The method of claim 17, wherein the at least one transducer has a fundamental frequency ranging from 10 KHz - 100 MHz.

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

20. The method of any one of claims 17-19, further comprising the step of delivering the medicament through a needle while the at least one transducer generates ultrasonic energy onto the needle hub.

Images