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Healthcare trends continue to move from hospital to home and many targeted therapies and precision medicines are now being designed to be self-administered by patients or delivered in a home setting. In the case of long acting injectables and bio-therapeutics, the importance of optimal drug/biologic-device combination in terms of user needs becomes critical for successful clinical outcomes. The risk especially increases for novel therapies due to unknowns and uncertainties surrounding new formulation flow behavior, delivery methods, new injection sites and therapeutic optimization. Other risk factors include patient tolerability and acceptability. The success of the clinical outcome is now dependent on the optimal delivery in these situations for a consistent pharmacokinetics (PK) response. In addition, the complexity of formulations and challenging delivery needs have brought to light some of the limitations of existing legacy device technology, which may not be suited for these novel applications. The formulation itself may not be an exact fit to deliver with existing standard device technologies and may need to be designed to deliver the specific formulation appropriately. Formulations may have to be optimized both for delivery and for the therapeutic outcome creating many iterative development cycles. Rapid development of the therapies requires simultaneous development of drug and device and thus the importance of early-stage characterization. We present a novel integrated approach that includes drug delivery optimization via an autoinjector simulator in pre-clinical and clinical studies to assess the PK performance and potential to establish path to device early on and reduce time to the clinic. [ABSTRACT FROM AUTHOR]

[Display omitted] Cavitation, the formation and collapse of vapor-filled bubbles, poses a problem in spring-driven autoinjectors (AIs). It occurs when the syringe accelerates abruptly during activation, causing pressure fluctuations within the liquid. These bubbles expand and then collapse, generating shock waves that can harm both the device and the drug molecules. This issue stems from the syringe's sudden acceleration when the driving rod hits the plunger. To better understand cavitation in AIs, we explore how design factors like drive spring force, air gap size, and fluid viscosity affect its likelihood and severity. We use a dynamic model for spring-driven autoinjectors to predict and analyze the factors contributing to cavitation initiation and severity. This model predicts the motion of AI components, such as the displacement and velocity of the syringe barrel, and allows us to investigate pressure wave propagation and the subsequent dynamics of cavitation under various operating conditions. We investigated different air gap heights (from 1 to 4 mm), drive spring forces (from 8 to 30 N), and drug solution viscosities (from 1 to 18 cp) to assess cavitation inception based on operational parameters. Results reveal that AI dynamics and cavitation onset and severity strongly depend upon AI operating parameters, namely drive spring force and air gap height. The maximum syringe acceleration increases with spring stiffness and decreases with air gap height; increases in air gap height prolong the time interval of syringe acceleration but diminish the maximum syringe acceleration. From actuation to injection, air gap pressure peaks twice, first due to impact with the rod/plunger and secondly due to the deacceleration event upon injection. The maximum air gap pressure increases with spring stiffness and decreases with air gap height. Results show that maximum cavitation bubble radii and collapse-driven extension rates occur with higher driver spring forces, smaller air gap heights, and less viscous solutions. A cavitation criterion is developed for cavitation in autoinjectors that concludes that cavitation in autoinjectors depends on the peak syringe acceleration. [ABSTRACT FROM AUTHOR]

Current parenteral administration of drugs suffers from several drawbacks including the requirement of healthcare personnel to administer the drug, the risk of needle stick injuries that may result in the transmission of blood borne pathogens, and patient discomfort. Prefilled devices have emerged as powerful tools to improve parenteral administration of drugs. There are a number of clinical conditions including treatment of endocrine diseases, neurological disorders, autoimmune diseases and emergency medicine where prefilled devices have made major improvements to patient care. Prefilled devices have become an important set of tools for the medical practitioner due to their ease of use and safety, cost effectiveness and patient convenience. This review provides a comprehensive summary of existing prefilled devices, their current clinical uses and corresponding regulatory processes. [ABSTRACT FROM AUTHOR]