Babaee Sahab, Hancock Matthew J, Barakat Joseph M, Vuong Brandon, Kowsari Kavin, Teller Sean S, Lu Lynn, Gonzalez Adriel, Persak Steven C, Rasheed Wail
Device Development and Technology, Merck Research Laboratories, Merck & Co., Inc, Rahway, NJ, 07065, USA.
Veryst Engineering LLC, Needham, MA, 02494, USA.
Drug Deliv Transl Res. 2025 Jul 16. doi: 10.1007/s13346-025-01898-6.
Autoinjectors with dual-chamber cartridges (AIDCs) are single-use, self-administrable injection devices that facilitate automated reconstitution and injection of lyophilized products. We report the development and application of a physics-based model to understand and optimize AIDC behavior, predicting its response as a function of formulation properties and injection device parameters. Our model is based on the equations of motion for the AIDC's dual stoppers, as well as the ideal gas law and an experimentally derived stopper friction vs. glide speed relationship. Our model provides estimates for some of the key essential performance requirements that yield good device performance, including injection time, stopper trajectories, and the maximum diluent volume. We validated our model using experimental injection time data demonstrating good agreement for a range of diluent volumes, reconstituted solution viscosities, and stopper positions. The model allows different device and formulation configurations to be tested virtually without requiring the physical device and formulation, reducing the need for extensive experimental testing and ensuring the robustness of the injector performance for successful drug delivery. The modeling framework applies to a broad class of spring-driven AIDCs for lyophilized drug and vaccine delivery and enables informed device selection through simulation-led technical due diligence.
带有双腔药筒的自动注射器（AIDC）是一次性的、可自行给药的注射装置，有助于对冻干产品进行自动复溶和注射。我们报告了一个基于物理的模型的开发和应用，以了解和优化AIDC的行为，预测其作为制剂特性和注射装置参数函数的响应。我们的模型基于AIDC双活塞的运动方程，以及理想气体定律和通过实验得出的活塞摩擦力与滑动速度的关系。我们的模型为一些能产生良好装置性能的关键基本性能要求提供了估计，包括注射时间、活塞轨迹和最大稀释剂体积。我们使用实验注射时间数据验证了我们的模型，结果表明在一系列稀释剂体积、复溶溶液粘度和活塞位置下，模型与实验数据吻合良好。该模型允许在几乎不需要实际装置和制剂的情况下对不同的装置和制剂配置进行虚拟测试，减少了大量实验测试的需求，并确保了注射器性能对于成功给药的稳健性。该建模框架适用于一大类用于冻干药物和疫苗递送的弹簧驱动AIDC，并通过基于模拟的技术尽职调查实现明智的装置选择。
