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Unraveling Pre-filled Syringe Needle Clogging: Exploring a Fresh Outlook Through Innovative Techniques

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Abstract

Objective

This study aimed to investigate the movement of liquid in the needle region of staked-in-needle pre-filled syringes using neutron imaging and synchrotron X-ray tomography. The objective was to gain insights into the dynamics of liquid presence and understand the factors contributing to needle clogging.

Methods

Staked-in-needle pre-filled syringes were examined using neutron radiography and synchrotron X-ray phase-contrast computed tomography. Neutron radiography provided a 2D visualization of liquid presence in the needle, while synchrotron X-ray tomography offered high-resolution 3D imaging to study detailed morphological features of the liquid.

Results

Neutron radiography revealed liquid presence in the needle region for as-received samples and after temperature and pressure cycling. Pressure cycling had a more pronounced effect on liquid formation. Synchrotron X-ray tomography confirmed the presence of liquid and revealed various morphologies, including droplets of different sizes, liquid segments blocking sections of the needle, and a thin layer covering the needle wall. Liquid presence was also observed between the steel needle and the glass barrel.

Conclusions

The combination of neutron imaging and synchrotron X-ray tomography provided valuable insights into the dynamics of liquid movement in staked-in-needle pre-filled syringes. Temperature and pressure cycling were found to contribute to additional liquid formation, with pressure changes playing a significant role. The detailed morphological analysis enhanced the understanding of microstructural arrangements within the needle. This research contributes to addressing the issue of needle clogging and can guide the development of strategies to improve pre-filled syringe performance.

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Acknowledgements

The authors would like to acknowledge Sun Qihang from Merck & Co., Inc. for the sample preparation.

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Authors and Affiliations

  1. Pharmaceutical Sciences and Clinical Supply, Merck & Co., Inc, Rahway, NJ, 07065, USA

    Guangli Hu, Daniel Bonanno, Yongchao Su, ** Zhao, Yogita Krishnamachari, William Forrest, Steven Persak & Jeffrey Givand

  2. ANAXAM, PARK INNOVAARE: deliveryLAB, CH-5234, Villigen, Switzerland

    David Mannes, Margie Olbinado, Matthias Wagner, Christian Grünzweig & Vladimir Novak

  3. Paul Scherrer Institute (PSI), Forschungsstrasse 111, 5232, Villigen, Switzerland

    David Mannes & Margie Olbinado

Authors
  1. Guangli Hu
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  2. Daniel Bonanno
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  3. Yongchao Su
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  4. ** Zhao
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  5. Yogita Krishnamachari
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  8. Jeffrey Givand
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  9. David Mannes
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  12. Christian Grünzweig
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  13. Vladimir Novak
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Correspondence to Guangli Hu or Yongchao Su.

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Hu, G., Bonanno, D., Su, Y. et al. Unraveling Pre-filled Syringe Needle Clogging: Exploring a Fresh Outlook Through Innovative Techniques. Pharm Res 41, 547–556 (2024). https://doi.org/10.1007/s11095-024-03673-7

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  • DOI: https://doi.org/10.1007/s11095-024-03673-7

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