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液体流变性能对弹簧驱动自动注射器注射过程的影响。

The role of liquid rheological properties on the injection process of a spring-driven autoinjector.

机构信息

School of Mechanical Engineering, Purdue University, West Lafayette, IN 47906, United States.

Eli Lilly and Company, Indianapolis, IN 46225, United States.

出版信息

Int J Pharm. 2022 Nov 25;628:122296. doi: 10.1016/j.ijpharm.2022.122296. Epub 2022 Oct 22.

Abstract

Accurate injection time prediction is essential in developing spring-driven autoinjector devices since the drug delivery is expected to finish within seconds to bring convenience, reduce the risk for early lift-off, and provide a consistent experience to users. The Carreau model captures the liquid's shear-dependent viscosity measured in our experiments. Thus, a quasi-steady model, which uses the Carreau model to describe the liquid's viscosity, is developed to predict the injection time of spring-driven autoinjectors. Analytical relations between the flow rate and the pressure drop in the needle are also obtained. The Carreau number in the spring-driven autoinjector is greater than one and smaller than a critical value; in this region, using the power-law model to describe the liquid viscosity accurately predicts the injection time, which agrees with the current literature findings. Additionally, a force threshold is identified for the friction force between the plunger and the syringe barrel, beyond which the injection time is infinite. Appreciation of this force threshold can help avoid device stalling and reduce the risk of underdosing. Moreover, the role of liquid's shear-thinning index on the injection time of spring-driven autoinjectors is quantified. Understanding the shear-thinning index allows formulators to experiment with excipients and pH to enhance confidence in drug/device combination product design and integration. Our experimental and theoretical results can help drug product and device developers with integrated product design and improve the patient experience.

摘要

准确的注射时间预测对于开发弹簧驱动自动注射器设备至关重要,因为期望药物输送能在几秒钟内完成,以带来便利、降低提前脱离的风险,并为用户提供一致的体验。Carreau 模型捕捉了我们实验中测量的液体的剪切依赖性粘度。因此,开发了一种准稳态模型,该模型使用 Carreau 模型来描述液体的粘度,以预测弹簧驱动自动注射器的注射时间。还获得了针头内流量和压降之间的解析关系。弹簧驱动自动注射器中的 Carreau 数大于 1 且小于临界值;在该区域中,使用幂律模型准确地描述液体粘度可以很好地预测注射时间,这与当前的文献发现一致。此外,确定了柱塞与注射器筒之间摩擦力的力阈值,超过该阈值,注射时间将变为无穷大。了解这个力阈值有助于避免设备停滞并降低剂量不足的风险。此外,还量化了液体的剪切稀化指数对弹簧驱动自动注射器注射时间的影响。了解剪切稀化指数可以帮助制剂人员通过实验改变赋形剂和 pH 值,从而增强对药物/器械组合产品设计和整合的信心。我们的实验和理论结果可以帮助药物产品和设备开发人员进行集成产品设计,并改善患者体验。

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