Reactive Impurities in Excipients

Reactive impurities in pharmaceutical excipients can affect drug product instability, leading to decreased product performance, loss in potency, and/or formation of potentially toxic degradants. The levels of reactive impurities in excipients may vary between lots and vendors. Screening of excipients for these impurities and a thorough understanding of their potential interaction with drug candidates during early formulation development can ensure robust drug product development. This chapter identifies the type and concentration of potentially reactive impurities in commonly used excipients. The excipient impurities are categorized into six major classes: reducing sugars, aldehydes, peroxides, metals, nitrate/nitrite, and organic acids. The sources/generation of these impurities, analytical methods for their detection and quantitation, stability of these impurities upon storage and processing, and their potential reactions with drug candidates are discussed. Specific examples of drug–excipient impurity interaction are presented as illustrative case studies. Mitigation strategies and corrective measures are also discussed.