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

Pharmaceutical Research volume 38, pages 257–275 (2021)Cite this article

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.

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Abbreviations

CFD:

Computational Fluid Dynamics

CFL:

Courant-Friedrichs-Lewy number

mAb:

Monoclonal antibody

SQ:

Subcutaneous

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Acknowledgments

This research was supported by a grant from the Eli Lilly and Company. Y. Z. acknowledges the support of Frederick N. Andrews Fellowship.

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Authors and Affiliations

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

    Yuchen Zhang, Dingding Han, Zhongwang Dou, Pavlos P. Vlachos & Arezoo M. Ardekani

  2. Eli Lilly and Company, Indianapolis, Indiana, USA

    Jean-Christophe Veilleux, Galen H. Shi & David S. Collins

Authors
  1. Yuchen Zhang
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  2. Dingding Han
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  3. Zhongwang Dou
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  4. Jean-Christophe Veilleux
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  5. Galen H. Shi
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  6. David S. Collins
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  7. Pavlos P. Vlachos
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  8. Arezoo M. Ardekani
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Correspondence to Arezoo M. Ardekani.

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Zhang, Y., Han, D., Dou, Z. et al. The Interface Motion and Hydrodynamic Shear of the Liquid Slosh in Syringes. Pharm Res 38, 257–275 (2021). https://doi.org/10.1007/s11095-021-02992-3

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  • DOI: https://doi.org/10.1007/s11095-021-02992-3

Key words

  • liquid slosh
  • air-liquid interface
  • autoinjector
  • protein denaturation