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      Microfluidic Delivery of High Viscosity Liquids Using Piezoelectric Micropumps for Subcutaneous Drug Infusion Applications

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          Abstract

          Goal: Auto-injectors for self-administration of drugs are usually refrigerated. If not warmed up prior to the injection, ejection of the total drug volume is not guaranteed, as their spring and plunger mechanism cannot adjust for a change in viscosity of the drug. Here, we develop piezoelectric micro diaphragm pump that allows these modifications possible while investigating the effectiveness of this alternative dosing method. Methods: The dosing of highly viscous liquid of 25 mPa·s is made possible using application-specific micropump design. By comparing the analytical with experimental results, the practicality of the concept is verified. Results: Using a powerful piezoelectric stack actuator, the micropump achieves high fluid pressures of up to (368 ± 17) kPa. In order to assess the influence of viscosity, we characterize the fluidic performance of the designed micropump through 27G gauge needle for various water-glycerin mixtures. We find maximum flow rates of 2 mL/min for viscosities of up to 25 mPa·s. Conclusions: The developed micro diaphragm pump enables the development of smart auto-injectors with flow rate regulation to achieve drug delivery for high viscosity drugs through 27G needles.

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          Does needle size matter?

          Hypodermic needles are in widespread use, but patients are unhappy with the pain, anxiety, and difficulty of using them. To increase patient acceptance, smaller needle diameters and lower insertion forces have been shown to reduce the frequency of painful injections. Guided by these observations, fine needles and microneedles have been developed to minimize pain and have found the greatest utility for delivery of vaccines and biopharmaceuticals such as insulin. However, pain reduction must be balanced against limitations of injection depth, volume, and formulations introduced by reduced needle dimensions. In some cases, needle-free delivery methods provide useful alternatives.
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            Subcutaneous Delivery of High-Dose/Volume Biologics: Current Status and Prospect for Future Advancements

            Abstract Subcutaneous (SC) delivery of biologics has traditionally been limited to fluid volumes of 1–2 mL, with recent increases to volumes of about 3 mL. This injection volume limitation poses challenges for high-dose biologics, as these formulations may also require increased solution concentration in many cases, resulting in high viscosities which can affect the stability, manufacturability, and delivery/administration of therapeutic drugs. Currently, there are technologies that can help to overcome these challenges and facilitate the delivery of larger amounts of drug through the SC route. This can be achieved either by enabling biologic molecules to be formulated or delivered as high-concentration injectables (>100 mg/mL for antibodies) or through facilitating the delivery of larger volumes of fluid (>3 mL). The SC Drug Delivery and Development Consortium, which was established in 2018, aims to identify and address critical gaps and issues in the SC delivery of high-dose/volume products to help expand this delivery landscape. Identified as a high priority out of the Consortium’s eight problem statements, it highlights the need to shift perceptions of the capabilities of technologies that enable the SC delivery of large-volume (>3 mL) and/or high-dose biologics. The Consortium emphasizes a patient-focused approach towards the adoption of SC delivery of large-volume/high-concentration dosing products to facilitate the continued expansion of the capabilities of novel SC technologies. To raise awareness of the critical issues and gaps in high-dose/volume SC drug development, this review article provides a generalized overview of currently available and emerging technologies and devices that could facilitate SC delivery of high-dose/volume drug formulations. In addition, it discusses the challenges, gaps, and future outlook in high-dose/volume SC delivery as well as potential solutions to exploit the full value of the SC route of administration.
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              Micropumps—past, progress and future prospects

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                Author and article information

                Contributors
                Journal
                IEEE Open J Eng Med Biol
                IEEE Open J Eng Med Biol
                0076400
                OJEMB
                IOJEA7
                IEEE Open Journal of Engineering in Medicine and Biology
                IEEE
                2644-1276
                2024
                18 January 2024
                : 5
                : 21-31
                Affiliations
                [1] institutionFraunhofer EMFT Institute for Electronic Microsystems and Solid-State Technologies, institutionringgold 201973; 80686 Munich Germany
                [2] institutionFraunhofer EMFT Institute for Electronic Microsystems and Solid-State Technologies, institutionringgold 201973; 80686 Munich Germany
                [3] institutionFraunhofer IMTE Research Institute for Individualized and Cell-based Medical Engineering, institutionringgold 591296; 23562 Lübeck Germany
                Article
                OJEMB-00074-2023
                10.1109/OJEMB.2024.3355692
                10939327
                38487095
                61213d6a-89c1-4518-accd-185e36fd98ab
                © 2024 The Authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License. For more information, see https://creativecommons.org/licenses/by-nc-nd/4.0/

                History
                : 24 July 2023
                : 13 November 2023
                : 15 January 2024
                : 15 January 2024
                : 23 February 2024
                Page count
                Figures: 10, Tables: 2, References: 44, Pages: 11
                Funding
                Funded by: institutionMoore4Medical project;
                Funded by: institutionElectronic Components and Systems for European Leadership Joint Undertaking;
                Funded by: institutionEuropean Union's H2020 Framework Program;
                Award ID: H2020/2014–2020
                Funded by: institutionNational Authorities;
                Award ID: H2020-ECSEL-2019-IA-876190
                This work was supported in part by the Moore4Medical project, which has received funding from the Electronic Components and Systems for European Leadership Joint Undertaking (ECSEL JU) in collaboration with the European Union's H2020 Framework Program under Grant H2020/2014–2020, and in part by the National Authorities, under Grant H2020-ECSEL-2019-IA-876190 www.moore4medical.eu.
                Categories
                Article

                27g needle,auto-injectors,high viscous mixtures,micropumps,piezoelectric stack actuator

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