胶塞对生物制品中不溶性微粒的影响研究  

Study on the influence of rubber stopper on sub-visible particles in biological products

作　　者：穆玲玲 彭缨[1] MU Lingling;PENG Ying(School of Wuya Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]沈阳药科大学无涯创新学院,辽宁沈阳110016

出　　处：《中国药剂学杂志(网络版)》2025年第1期1-8,共8页Chinese Journal of Pharmaceutics:Online Edition

摘　　要：目的旨在探讨胶塞对单克隆抗体产品中不溶性微粒的影响,并初步明确其与生物制品稳定性之间的关联。方法采用流式成像颗粒分析系统(Flow-Cam 8100)对初始制备和高温条件下放置的单抗蛋白溶液、单抗蛋白缓冲液、微粒检查用水中析出的不溶性微粒数量和形态进行分析;使用Waters HPLC对40℃高温条件下倒置0、7、15天的单抗产品SEC-HPLC纯度进行检测;通过应力条件,对比同一厂家但不同规格和不同厂家生产的胶塞中硅油的含量。结果通过Flow-Cam 8100系统识别出待研究的单抗产品中80%以上的不溶性微粒为硅油,且大小集中在1~10μm。在温度和时间的共同作用下,胶塞中的硅油会逐步迁移到产品中,加速聚体生成,降低SEC-HPLC纯度。同一厂家但不同规格和不同厂家生产的胶塞中硅油含量存在显著性差异,在进行内包装材料选择时需要关注其与产品的相容性。结论本研究揭示了胶塞对单克隆抗体产品中不溶性微粒的影响,并初步明确其与产品稳定性之间的关联,为制剂内包装材料胶塞的选择提供参考。Objective To investigate the effects of rubber stopper on sub-visible particles in monoclonal antibody products and to clarify the potential relationship between sub-visible particles and the stability of biological products.Methods Flow-Cam 8100 system was used to examine the quantity and morphology of sub-visible particles formed from the monoclonal antibody protein solution,monoclonal antibody protein buffer and water after incubation at 40℃for varied time points.Waters HPLC was used to analyze the purity of monoclonal antibody products stored for 0 day,7 days and 15 days at 40℃by SEC-HPLC.The content of silicone oil in rubber stoppers produced by different manufacturers and different specifications of the same manufacturer were compared after stress condition.Results It was found that more than 80%of the sub-visible particles in the monoclonal antibody products were silicone oil and the size was enriched between 1~10μm.Under the combined action of temperature and time,silicone oil would further migrate to the product and finally accelerated the decrease of product purity shown by SEC-HPLC.There were significant differences in silicone oil content in rubber stoppers produced by different manufacturers and different specifications of the same manufacturer,therefore,it is necessary to pay attention to the compatibility between rubber stoppers and products when selecting primary packaging materials.Conclusions This study reveals the effects of rubber stoppers on sub-visible particles in products,and the relationship between stoppers and the stability of monoclonal antibody products,which provide reference for the selection of rubber stopper.

关 键 词：不溶性微粒 硅油 胶塞 单克隆抗体 

分 类 号：R94[医药卫生—药剂学]