School of Mechanical Engineering, Purdue University, West Lafayette, IN 47906, United States.
School of Mechanical Engineering, Purdue University, West Lafayette, IN 47906, United States; Eli Lilly and Company, Indianapolis, IN 46225, United States.
Int J Pharm. 2024 Mar 5;652:123753. doi: 10.1016/j.ijpharm.2023.123753. Epub 2023 Dec 28.
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.
空化现象,即充满蒸汽的气泡的形成和破裂,给弹簧驱动式自动注射器(AIs)带来了问题。当注射器在激活过程中突然加速时,会发生这种现象,导致液体内部压力波动。这些气泡会膨胀然后破裂,产生冲击波,从而对设备和药物分子造成损害。这个问题源于驱动杆撞击柱塞时注射器的突然加速。为了更好地理解 AIs 中的空化现象,我们探讨了设计因素,如驱动弹簧力、气隙大小和流体粘度,如何影响其发生的可能性和严重程度。我们使用弹簧驱动式自动注射器的动态模型来预测和分析导致空化起始和严重程度的因素。该模型预测了 AI 组件的运动,如注射器筒的位移和速度,并使我们能够在各种操作条件下研究压力波传播和随后的空化动力学。我们研究了不同的气隙高度(从 1 到 4 毫米)、驱动弹簧力(从 8 到 30 牛)和药物溶液粘度(从 1 到 18 厘泊),以根据操作参数评估空化起始。结果表明,AI 动力学和空化起始以及严重程度强烈取决于 AI 操作参数,即驱动弹簧力和气隙高度。随着弹簧刚度的增加和气隙高度的减小,注射器的最大加速度增加;气隙高度的增加延长了注射器加速的时间间隔,但减小了注射器的最大加速度。从启动到注射,气隙压力峰值出现两次,第一次是由于与杆/柱塞的撞击,第二次是由于注射时的减速事件。最大气隙压力随弹簧刚度的增加和气隙高度的减小而增加。结果表明,最大空化气泡半径和由空化气泡破裂驱动的延伸率出现在更高的驱动弹簧力、更小的气隙高度和更小的粘性溶液中。为自动注射器中的空化现象制定了一个空化准则,该准则表明自动注射器中的空化取决于峰值注射器加速度。