Effect of Residual Reactive Impurities in Excipients on the Stability of Pharmaceutical Products

This chapter focuses on residual impurities commonly present in excipients and the reactivity of these impurities that leads to degradation of the drug product. It discusses various strategies used to understand the mechanism of such degradation pathways and the use of this knowledge in identifying incompatibilities between drug–excipient combinations. The chapter also focuses on various measures and mitigation strategies that are often employed to prevent active pharmaceutical ingredient degradation, as well as the role of environmental factors packaging and storage conditions in ensuring the quality of a pharmaceutical drug product. It examines various types of residual reactive impurities in excipients and their confounding effects on stability, efficacy, safety, and overall performance of pharmaceutical products. The oxidative degradation of polyethylene glycol and polysorbate excipients, in particular, initially results in the formation of aldehyde impurities that can undergo further oxidation to form both formic and acetic acid.