Comparative Delamination Study to Demonstrate the Impact of Container Quality and Nature of Buffer System

Abstract

Delamination of flakes in glass containers used for primary drug packaging has become a serious quality concern in recent years. Because glass delamination typically occurs weeks/months after filling and there are a variety of container, processing and drug formulation factors that contribute to glass delamination, it is recommended according to USP <1660> (1) to conduct suitable container/drug product compatibility tests. Such predictive studies should give results that allow a graduated assessment for increasing risk of delamination that can be used to detect early stages of this phenomenon and to help to select appropriate container/formulation systems to proactively prevent delamination instead of just monitoring for the presence/absence of flakes. This work demonstrates the capability of a container compatibility testing approach by determining the impact of three different model buffer/solution systems (citrate, phosphate and sodium bicarbonate) with the delamination behavior of two different types of 2 mL glass vials, standard quality and delamination controlled quality. Vials of each type were filled and stored up to 48 weeks at 40 °C. Using a USP <1660>–compatible package of different analytical methods clearly demonstrates the significant influence of both vial quality and chemistry of the content on glass delamination propensity.

LAY ABSTRACT The detachment of flakes from the inner surface of a glass container—also referred to as delamination—has become a serious quality concern over the last years for the pharmaceutical industry. Chapter <1660> of the United Stated Pharmacopeia therefore recommends performing predictive screening studies with the drug formulation and the glass container to evaluate the risk of delamination in an early stage of the drug development. Predictive screening studies have been performed with three different representative buffer/solution and glass vials of two different quality steps (standard and delamination controlled). The results demonstrate the capability of container compatibility testing and the influence of vial quality and chemistry of the content on glass delamination propensity.