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注射器内液体晃动的界面运动与流体动力剪切

The Interface Motion and Hydrodynamic Shear of the Liquid Slosh in Syringes.

作者信息

Zhang Yuchen, Han Dingding, Dou Zhongwang, Veilleux Jean-Christophe, Shi Galen H, Collins David S, Vlachos Pavlos P, Ardekani Arezoo M

机构信息

Department of Mechanical Engineering, Purdue University, West Lafayette, Indiana, USA.

Eli Lilly and Company, Indianapolis, Indiana, USA.

出版信息

Pharm Res. 2021 Feb;38(2):257-275. doi: 10.1007/s11095-021-02992-3. Epub 2021 Feb 22.

Abstract

PURPOSE

Interface motion and hydrodynamic shear of the liquid slosh during the insertion of syringes upon autoinjector activation may damage the protein drug molecules. Experimentally validated computational fluid dynamics simulations are used in this study to investigate the interfacial motion and hydrodynamic shear due to acceleration and deceleration of syringes. The goal is to explore the role of fluid viscosity, air gap size, syringe acceleration, syringe tilt angle, liquid-wall contact angle, surface tension and fill volume on the interface dynamics caused by autoinjector activation.

METHODS

A simplified autoinjector platform submerged in water is built to record the syringe and liquid motion without obstruction of view. The syringe kinematics is imported to the simulations based on OpenFOAM InterIsoFoam solver, which is used to study the effects of various physical parameters.

RESULTS

The simulations agree with experiments on the air-liquid interface profile and interface area. The interfacial area and the volume of fluid subject to high strain rate decrease with the solution viscosity, increase with the air gap height, syringe velocity, tilt angle and syringe wall hydrophobicity, and hardly change with the surface tension and liquid column height. The hydrodynamic shear mainly occurs near the syringe wall and entrained bubbles.

CONCLUSION

For a given dose of drug solution, the syringe with smaller radius and larger length will generate less liquid slosh. Reducing the air volume and syringe wall hydrophobicity are also helpful to reduce interface area and effective shear. The interface motion is reduced when the syringe axis is aligned with the gravitational direction.

摘要

目的

自动注射器激活后注射器插入过程中液体晃动的界面运动和流体动力剪切可能会损害蛋白质药物分子。本研究使用经过实验验证的计算流体动力学模拟来研究由于注射器加速和减速引起的界面运动和流体动力剪切。目标是探讨流体粘度、气隙尺寸、注射器加速度、注射器倾斜角度、液 - 壁接触角、表面张力和填充体积对自动注射器激活引起的界面动力学的作用。

方法

构建一个浸没在水中的简化自动注射器平台,以记录注射器和液体的运动且无视线阻挡。基于OpenFOAM InterIsoFoam求解器将注射器运动学导入模拟中,用于研究各种物理参数的影响。

结果

模拟结果与气液界面轮廓和界面面积的实验结果一致。高应变率下的界面面积和流体体积随溶液粘度降低,随气隙高度、注射器速度、倾斜角度和注射器壁疏水性增加,而随表面张力和液柱高度几乎不变。流体动力剪切主要发生在注射器壁和夹带气泡附近。

结论

对于给定剂量的药物溶液,半径较小且长度较大的注射器产生的液体晃动较小。减少空气体积和注射器壁疏水性也有助于减少界面面积和有效剪切。当注射器轴与重力方向对齐时,界面运动减少。

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