Zhao Jianxiu, Lavalley Virginie, Mangiagalli Paolo, Wright Justin M, Bankston Theresa E
BD Medical-Pharmaceutical Systems, One Becton Drive, Franklin Lakes, New Jersey, 07417, USA.
AAPS PharmSciTech. 2014 Dec;15(6):1398-409. doi: 10.1208/s12249-014-0167-y. Epub 2014 Jun 18.
The occurrence of glass delamination is a serious concern for parenteral drug products. Over the past several years, there has been a series of product recalls involving glass delamination in parenteral drugs stored in vials which has led to heightened industry and regulatory scrutiny. In this study, a two-pronged approach was employed to assess the inner surface durability of vials and pre-filled syringes. Non-siliconized syringes were used in order to directly compare glass to glass performance between vials and syringes. The vial and syringe performance was screened with pharmaceutically relevant formulation conditions. The influence of pH, buffer type, ionic strength, and glass type and source was evaluated. In addition, an aggressive but discriminating formulation condition (glutaric acid, pH 11) was used to ascertain the impact of syringe processing. Advanced analytical tools including inductively coupled plasma/mass spectrometry, scanning electron microscopy, atomic force microscopy, and dynamic secondary ion mass spectroscopy showed significant differences in glass performance between vials and syringes. Pre-filled syringes outperform vials for most tests and conditions. The manufacturing conditions for vials lead to glass defects, not found in pre-filled syringes, which result in a less chemically resistant surface. The screening methodology presented in this work can be applied to assess suitability of primary containers for specific drug applications.
玻璃分层现象的出现是注射用药品面临的一个严重问题。在过去几年里，发生了一系列涉及储存在小瓶中的注射用药品玻璃分层的产品召回事件，这使得行业和监管审查力度加大。在本研究中，采用了双管齐下的方法来评估小瓶和预填充注射器的内表面耐久性。使用了未硅化的注射器，以便直接比较小瓶和注射器之间玻璃与玻璃的性能。在与药学相关的制剂条件下筛选小瓶和注射器的性能。评估了pH值、缓冲液类型、离子强度以及玻璃类型和来源的影响。此外，还使用了一种苛刻但具有区分性的制剂条件（戊二酸，pH值11）来确定注射器加工的影响。包括电感耦合等离子体/质谱、扫描电子显微镜、原子力显微镜和动态二次离子质谱在内的先进分析工具显示，小瓶和注射器的玻璃性能存在显著差异。在大多数测试和条件下，预填充注射器的性能优于小瓶。小瓶的制造条件会导致玻璃缺陷，而预填充注射器中不存在这种缺陷，这会导致表面的化学耐受性较差。本研究中提出的筛选方法可用于评估特定药物应用中一级包装容器的适用性。
