Eshraghi Javad, Veilleux Jean-Christophe, Shi Galen, Collins David, Ardekani Arezoo M, Vlachos Pavlos P
Department of Mechanical Engineering, Purdue University, West Lafayette, IN, 47907, USA.
Eli Lilly and Company, Indianapolis, IN, USA.
Pharm Res. 2022 Sep;39(9):2247-2261. doi: 10.1007/s11095-022-03334-7. Epub 2022 Jul 19.
Cavitation is an undesired phenomenon that may occur in certain types of autoinjectors (AIs). Cavitation happens because of rapid changes of pressure in a liquid, leading to the formation of small vapor-filled cavities, which upon collapsing, can generate an intense shock wave that may damage the device container and the protein drug molecules. Cavitation occurs in the AI because of the syringe-drug relative displacement as a result of the syringe's sudden acceleration during needle insertion and the ensuing pressure drop at the bottom of the container. Therefore, it's crucial to analyze the potential effect of cavitation on AI. The goal of the current study is to investigate the effects of syringe and AI design parameters such as air gap size, syringe filling volume, fluid viscosity, and drive spring force (syringe acceleration) on the risk and severity of cavitation.
A model autoinjector platform is built to record the syringe and cavitation dynamics which we use to estimate the cavitation intensity in terms of extension rate and to study the effects of design parameters on the severity of cavitation.
Our results show the generation of an intense shock wave and a high extension rate upon cavitation collapse. The induced extension rate increases with syringe acceleration and filling volume and decreases with viscosity and air gap size.
The most severe cavitation occurred in an AI device with the larger drive spring force and the syringe of a smaller air gap size filled with a less viscous fluid and a larger filling volume.
空化是一种可能在某些类型的自动注射器(AI)中出现的不良现象。空化的发生是由于液体中压力的快速变化,导致形成充满蒸汽的小空腔,这些空腔在坍塌时会产生强烈的冲击波,可能会损坏设备容器和蛋白质药物分子。在自动注射器中,由于在针头插入过程中注射器突然加速以及容器底部随之出现的压力下降,导致注射器与药物的相对位移,从而引发空化现象。因此,分析空化对自动注射器的潜在影响至关重要。本研究的目的是调查注射器和自动注射器设计参数,如气隙大小、注射器填充体积、流体粘度和驱动弹簧力(注射器加速度)对空化风险和严重程度的影响。
构建一个模型自动注射器平台,以记录注射器和空化动力学,我们用其根据伸展率估算空化强度,并研究设计参数对空化严重程度的影响。
我们的结果显示,空化坍塌时会产生强烈的冲击波和高伸展率。诱导伸展率随注射器加速度和填充体积的增加而增加,随粘度和气隙大小的减小而减小。
在具有较大驱动弹簧力、气隙尺寸较小的注射器、填充低粘度流体且填充体积较大时的自动注射器设备中,空化最为严重。