(632b) API Impurity Control - Utilizing Kinetic Modeling to Understand a Dynamic Reaction System

A fundamental understanding of the process parameters impacting the kinetics of both desired and undesired reactions is critical for achieving the high degree of impurity control required in the pharmaceutical industry. This submission will discuss impurity kinetic studies that enabled a robust manufacturing process for the final synthetic step of a drug. Two factors make this system particularly interesting. First, the undesirable side reaction occurs during a distillation where the solvent composition, temperature, and concentration change over time. Second, the impurity formation has been found to be autocatalytic. The result is that the rate of impurity formation monotonically increases as the unit operation progresses. The presentation will discuss laboratory studies, a model which combines kinetic and VLE equations to accurately represent this dynamic system, and ramifications for the manufacturing process.