Clogging prevention of needle-based delivery devices

Abstract

An injection device includes a reservoir for containing a medicament, a needle having a needle fluid path in communication with the reservoir and configured to deliver the medicament to a patient's body at a needle tip, and an anti-clogging substance disposed within the needle fluid path, the anti-clogging substance being configured and arranged to form a fluid barrier between the medicament and the needle tip.

Description

CLOGGING PREVENTION OF NEEDLE-BASED DELIVERY DEVICESCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The application claims the benefit of priority to U.S. Provisional Application No. 63 / 598,193, filed November 13, 2023. the contents of each of which are incorporated herein by reference in their entirety.FIELD OF THE INVENTION

[0002] The present disclosure relates generally to syringes and injectors. More specifically, the present disclosure relates to device 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 pre-filled syringe delivery devices, which are prone to needle clogging. It has been theorized that the needle clogging phenomenon is stochastic in nature and occurs during a combination of normal manufacturing, transportation, and storage of the pre-filled syringe combination product. The current hypothesis suggests that the drug product migrates into the fluid path of the needle during typical pressure / temperature differentials that occur during manufacturing (e.g., filling and stoppering) and / or transportation (e.g., air shipment). Once drug product has entered the needle fluid path there is potential for water vapor transmission to occur through the pre-filled 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. When the needle clogging phenomenon occurs, it prevents the end user (e.g., health care 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 / 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.

[0004] Thus, there exists a need for devices that improve upon and advance the methods of safely using injectors and syringes, such as pre-filled syringes, and to reduce the possibility’ of clogging during use.SUMMARY OF THE INVENTION

[0005] In one embodiment, an injection device includes a reservoir for containing a medicament, a needle having a needle fluid path in communication with the reservoir and configured to deliver the medicament to a patient’s body at a needle tip, and an anti-clogging substance disposed within the needle fluid path, the anti-clogging substance being configured and arranged to form a fluid barrier between the medicament and the needle tip.BRIEF DESCRIPTION OF THE DRAWINGS

[0006] Various embodiments of the presently disclosed syringes are disclosed herein with reference to the drawings, wherein:

[0007] FIG. 1 is a schematic front view of a pre-filled syringe.

[0008] FIGS. 2A-2B are magnified photographs showing blockages of dried formulation at the needle tip.

[0009] FIGS. 3A-3B are side-by-side schematic views of a pre-filled syringe without and with an anti-clogging substance.

[0010] FIG. 4 is a schematic front view of a multi-cartridge injection system.

[0011] 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

[0012] Despite the various improvements that have been made to injectors and syringes, such as pre-filled syringes, conventional methods suffer from some shortcomings as discussed above.

[0013] 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.

[0014] 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.

[0015] Likewise, the terms “trailing” and “leading” are to be taken as relative to the operator’s fingers (e.g., physician) from 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.

[0016] Reference is now made to FIG. 1, which shows an exemplary prefilled-syringe 100 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 pre-filled 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.). Pre-filled syringe 100 generally comprises two main portions, a plunger rod assembly 1 10 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.

[0017] 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. 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.

[0018] FIG. 2A-2B are magnified photographs show ing a needle 134 and blockages of dried formulation 180 at the needle tip within needle fluid path 139. As briefly described above, these blockages or occlusions form when the drug product crystalizes from exposure to, for example, water vapor, to create a solid-like particles which can result in needle clogging to cause full or partial occlusions. Specifically, 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.

[0019] FIGS. 3A-3B illustrate one potential solution for to this problem by preventing the ability of a drug product to migrate into the needle fluid path and be exposed to water vapor. In FIG. 3 A, a needle 300 A extends between a proximal end 312 and a distal end 314, and includes a drug product 320 in reservoir R, which extends into fluid path 139 of needle 134, the needle terminating at needle tip 137. In this example, fluid path 139 has a length LI. Air bubbles 310A may also be present in the barrel proximal drug product 320. This configuration is at an increased risk of clogging. Thus, to prevent or reduce the risk of clogging, a needle 300B as shown in FIG.3B may extend between a proximal end 312 and a distal end 314, and include a drug product 320 in reservoir R, which may extend partially into fluid path 139 of needle 134. In this example, an anti-clogging substance 350 is disposed within fluid path 139 of needle 134, distal to drug product 320. In the example show n, anti-clogging substance 350 fills approximately half the volume of fluid path 139. It will be understood that anti-clogging substance 350 may fill the entire volume of fluid path 139, 2 / 3 of the volume of fluid path 139, 14 of the volume of fluid path 139. 1 / 3 of the volume of fluid path 139.lA of the volume of fluid path 139 or less thanlA of the volume of fluid path 139. In at least some examples, 60-90% of the volume of the anticlogging substance 350 is disposed within the needle fluid path. In at least some examples, about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90%, of the volume of the anti-clogging substance 350 is disposed within the needle fluid path. The presence of anti-clogging substance 350 may form a fluid barrier between the drug product and the environment to prevent water vapor from reaching the drug product and drying it out within the needle fluid path 139. As disclosed herein, the term “fluid barrier” is used to describe a separation betw een the contents of the syringe (e.g., the medicament) and the ambient atmosphere (e.g., water vapor).

[0020] Anti-clogging substance 350 may include one or more suitable bio-compatible material(s) having an acceptable viscosity, such as an oil. Such oil(s) can be any appropriate pharmaceutical grade oil that is suitable for subcutaneous injections. In at least some examples, anti-clogging substance 350 may include any biocompatible oil. In at least some examples, anticlogging substance 350 may include soybean oil. Alternatively, anti-clogging substance 350 may include any vaccine adjuvant. Conventional adjuvants, well-known in the art are e.g., Freund’s Complete and Incomplete adjuvant, vitamin E, non-ionic block polymers, muramyl dipeptides, Quill A(R), mineral oil e.g., Bayol ® or Markol ®, vegetable oil, and Carbopol ® (a homopolymer), or Diluvac ® Forte. The vaccine may also comprise a so-called "vehicle". A vehicle is a compound to which the polypeptide adheres, without being covalently bound to it. Often used vehicle compounds are e.g., aluminum hydroxide, -phosphate or -oxide, silica, Kaolin, and Bentonite.In some examples, the anti-clogging substance may also comprise a wetting agent or a viscosity enhancing agent. A preferred viscosity enhancing agent is sodium carboxymethyl cellulose, although other suitable viscosity enhancing agents may also be used. The anti-clogging substance may also comprise a density enhancing agent that increases the density of the anti-clogging substance. A preferred density enhancing agent is sorbitol, although other suitable density enhancing agents may also be used. The anti -clogging substance may also comprise a tonicity adjusting agent to adjust the tonicity to preclude toxicity problems andimprove biocompatibility. A preferred tonicity adjusting agent is sodium chloride, although other suitable tonicity adjusting agents may also be used.

[0021] Preferred wetting agents may include polysorbate 20 (Tween 20), polysorbate 40 (Tween 40), and polysorbate 80 (Tween 80). One example of an anti-clogging substance may include a wetting agent that comprises 1.5% sodium carboxymethyl cellulose, 30% sorbitol, and 0.2% polysorbate 20. Another example of a wetting agent may include comprises 3% sodium carboxymethyl cellulose, 0.9% saline, and 0.1% polysorbate 20.

[0022] Anti-clogging substance 350 may be introduced into fluid path 139 of needle 134 in several ways. For example, anti -clogging substance 350 may be used to completely prime the full length of needle 134 prior to the drug product filling and stoppering process. With the needle fluid path completely primed with substance 350 and sealed on the distal end by the rigid needle shield component, the substance may be fixed or suspended within fluid path 139. As described, it is also possible to prime less than the entirely of the needle fluid path. The substance 350 may be introduced and / or injected through the proximal end of the reservoir. Alternatively, the entire needle 134 or a portion of needle 134 may be dipped into a reservoir of substance 350 to a predetermined depth to draw or wick a certain amount of substance 350 into the fluid path 139 of needle 134. In such examples, the reliance on a capillary effect may be useful. The needle 134 may also be bathed within substance 350. Without being bound by any particular theory, it is believed that the presence of substance 350 within fluid path 139 at a position distal to the drug product would eliminate or reduce the possibility for the drug product to enter the fluid path 139, crystalize and clog the needle. In some examples, anti-clogging substance 350 in the needle tip may be processed at the pre-filled syringe manufacturer’s end as part of needle siliconization process before capping the rigid need shield.EXAMPLE 1

[0023] In an experiment to explore the effects of potential anti-clogging substances, devices filled with drug product were stored in 5 °C for 24 hours with their rigid needle shield removed. The rigid needle shield was purposely removed for this study to accelerate the process of drug product drying (i.e., crystallization). The study utilized a total ofN=12 pre-filled syringe products. Half of the samples (N=6) did not contain any substance in the needle fluid path, and the other half of the samples (N=6) had their needle fluid paths completely primed with soybean oil. After all the samples were staged in 5 °C climatic condition for 24 hours, they were evaluated for needle clogging. The needle clogging performance was evaluated by performing a typical injection force test on INSTRON ® tensile / compression testing equipment. Any sample testedthat exceeded an injection force of 33N (injection force requirement for drug product) was considered to have a clogged needle. The results of this study were as follows:1. Control Samples (i.e., no anti-clogging substance): 3 out of 6 samples exhibited a clogged needle.2. Test Samples (i.e., fully primed soybean oil): 0 out of 6 samples exhibited needle clogging.

[0024] Thus, in this example, the use of a fully primed soybean oil needle reduced the likelihood of needle clogging.

[0025] The principles of the present disclosure may be useful for other needle-based syringes or injector systems. 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 "CY”. 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, 412b that terminate in couplers for mating with stoppers 430a, 430b.

[0026] Injector 400 further includes a containment unit 440 that includes a pair of barrels 441a, 441b. In some examples, each of barrels 441a, 441b is substantially cylindrically-shaped and each includes a sidewall 444a, 444b and a respective lumen 442a, 442b for accepting at least a portion of stems 412a, 412b and stoppers 430a, 430b. Barrels 441a. 441b may terminate in openings 446a. 446b close to the distal end 404. In some examples, the two barrels 441a, 441b are disposed side-by-side and may be joined at a common wall 448. Optionally, each of barrels 441a, 441b may include a respective rectangular window 449a, 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 a bottom of a barrel and the windows 449a, 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.

[0027] The containment unit may be used to hold the two separate container closure systems during packaging and shipping. Specifically, each barrel 441a, 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.

[0028] 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 may define a continuous lumen from each of the branches 452 down to the common hollow shaft, 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, 441b.

[0029] Y-shaped conduit 450 may be partially disposed within each of barrels 441 a, 44 lb, and common hollow shaft 454 may be at least partially disposed within cap 460. Cap 460 may be funnel-shaped at a first end 462 and have a luer-fitting 464 at an opposite second end 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 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 and the probe needle into the patient with the application of pressure to the plunger rod. In one embodiment, cap 450 is engaged by a press-fit or similar mechanism to the containment unit.

[0030] 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 delivery 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 fewer 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.

[0031] 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. Tw o separate vials or containers may be inserted into barrels 441 a, 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 (not show n) 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, 430b and translates themthrough the barrels 441a.441b, causing the contents of the containers to flow through Y-shaped conduit and the probe needle into the patient’s body.

[0032] In this example, an anti-clogging substance 350 has been introduced within needle 434 to prevent the contents of either barrel from traveling to the distal end of the needle, to be exposed to water vapor and crystalize and / or clog the needle. As previously discussed, the anticlogging substance 350 may include soybean oil or other suitable material, and the substance may be introduced into the fluid path via any of the described techniques (e.g.. injection, dipping, bathing, coating, etc.).

[0033] 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 volume and material for the anti-clogging substance may be varied. 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.

[0034] 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 having a needle fluid path in communication with the reservoir and configured to deliver the medicament to a patient's body at a needle tip; and an anti-clogging substance disposed within the needle fluid path, the anti-clogging substance being configured and arranged to form a fluid barrier between the medicament and the needle tip.

2. The inj ection device of claim 1. wherein the anti-clogging substance fills an entirety of the needle fluid path.

3. The injection device of claim 1, wherein the anti-clogging substance fills half a volume of the needle fluid path.

4. The injection device of claim 1, wherein the anti-clogging substance fills less than one-quarter of a volume of the needle fluid path.

5. The injection device of claim 1, wherein the anti-clogging substance is biocompatible.

6. The injection device of claim 5, wherein the anti-clogging substance comprises an oil.

7. The injection device of claim 6, wherein the anti-clogging substance comprises soy bean oil.

8. The injection device of claim 1, wherein the medicament comprises a high concentration drug product disposed within the reservoir.

9. The injection device of claim 1, wherein the injection device is a pre-filled syringe.

10. A method of preventing clogging of an injection device comprising:providing a reservoir for containing a medicament, and a needle having a needle fluid path in communication with the reservoir and configured to deliver the medicament to a patient's body at a needle tip; and introducing an anti-clogging substance within the needle fluid path, the anti-clogging substance being configured and arranged to form a fluid barrier between the medicament and the needle tip.

11. The method of claim 10, wherein introducing an anti-clogging substance comprises introducing an oil within the needle fluid path.

12. The method of claim 11 , wherein introducing an anti-clogging substance comprises introducing soybean oil within the needle fluid path.

13. The method of claim 10, wherein introducing an anti-clogging substance comprises injecting an anti-clogging substance into the needle fluid path.

14. The method of claim 10, wherein introducing an anti-clogging substance comprises dipping the needle in an anti-clogging substance and allowing the anti-clogging substance to wick into the needle fluid path.

15. The method of claim 10, wherein introducing an anti-clogging substance comprises bathing the needle in an anti-clogging substance.

16. The method of claim 10, wherein introducing an anti-clogging substance comprises filling the entire needle fluid path with the anti-clogging substance.

17. The method of claim 10, wherein introducing an anti-clogging substance comprises filling half a volume of the needle fluid path with the anti-clogging substance.

18. The method of claim 10, wherein introducing an anti-clogging substance comprises filling less than one-quarter of a volume of the needle fluid path with the anti-clogging substance.

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