Investigating Zinc Migration from Rigid Needle Shield to Drug Formulation in Needle Tip of Pre-filled Syringe.

IF 4.3 3区医学 Q2 CHEMISTRY, MULTIDISCIPLINARY

Pharmaceutical Research Pub Date : 2025-08-01 Epub Date: 2025-07-29 DOI:10.1007/s11095-025-03888-2

Guangli Hu, Chengbei Li, Kaitlin Wang, Yongchao Su, William Forrest, Jeffrey Givand, Dario Ferreira Sanchez, Margie Olbinado, Matthias Wagner, Christian Grünzweig, Vladimir Novak

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引用次数: 0

Abstract

Objective: This study investigates the underexplored mechanisms of needle clogging in pre-filled syringes (PFSs), focusing on zinc (Zn) ions, which have been reported to promote protein gelation and increase formulation viscosity. We present direct evidence of Zn migration from the rigid needle shield (RNS) into drug products, aiming to elucidate the migration pathways and the role of Zn in clogging.

Methods: Pre-filled syringes containing a therapeutic monoclonal antibody (mAb) were stored at 5°C and subjected to stress conditions at 40°C for up to six months. Inductively coupled plasma mass spectrometry (ICP-MS) measured metal ion levels, while synchrotron-based X-ray phase-contrast computed tomography (SR-XPCT) and X-ray fluorescence (SR-XRF) provided in situ visualization of Zn distribution in dry materials under stress.

Results: We found that Zn leaches from the RNS into the drug formulation during liquid-RNS contact. ICP-MS revealed higher Zn levels, along with aluminum and titanium, in clogged needles compared to clean ones. SR-XRF identified Zn hot spots within the dried drug product, while SR-XPCT displayed 3D visualization of Zn particle accumulation at the needle tip. Notably, Zn migration accelerated at 40°C, with minimal detection at 5°C, indicating the significant influence of temperature.

Conclusions: This study offers the first experimental evidence of Zn migration from the RNS into drug formulations within staked-in-needle PFSs. While Zn is not solely responsible for needle clogging, its presence in both RNS and the drug suggests a contributory role. These insights can inform strategies for improving PFS performance and reliability.

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预充式注射器针尖锌从刚性针罩向药物制剂迁移的研究。

目的：本研究探讨预充式注射器（pfs）中针头堵塞的机制，重点研究锌（Zn）离子，锌离子已被报道促进蛋白质凝胶化并增加配方粘度。我们提供了锌从刚性针屏蔽（RNS）迁移到药物制品的直接证据，旨在阐明迁移途径和锌在堵塞中的作用。方法：将含有治疗性单克隆抗体（mAb）的预充注射器保存在5°C，并在40°C的应激条件下保存长达6个月。电感耦合等离子体质谱（ICP-MS）测量金属离子水平，而基于同步加速器的x射线相衬计算机断层扫描（SR-XPCT）和x射线荧光（SR-XRF）提供了应力下干燥材料中Zn分布的原位可视化。结果：我们发现锌在液体-RNS接触过程中从RNS中浸出到药物制剂中。ICP-MS显示，与干净的针头相比，堵塞针头中的锌、铝和钛含量更高。SR-XRF识别了干燥药品内的锌热点，而SR-XPCT显示了针尖锌颗粒积聚的三维可视化。值得注意的是，Zn在40°C时迁移加速，在5°C时迁移最少，说明温度的影响显著。结论：本研究提供了Zn从RNS迁移到针内pfs内药物制剂的第一个实验证据。虽然锌不是导致针头堵塞的唯一原因，但它在RNS和药物中的存在表明它起了一定的作用。这些见解可以为提高PFS性能和可靠性的策略提供信息。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmaceutical Research 医学-化学综合

CiteScore

6.60

自引率

5.40%

发文量

276

审稿时长

3.4 months

期刊介绍： Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to: -(pre)formulation engineering and processing- computational biopharmaceutics- drug delivery and targeting- molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)- pharmacokinetics, pharmacodynamics and pharmacogenetics. Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.