(103b) Process Analytical Technology for Crystallization Processes

This presentation provides an overview of the state-of-the-art in the application of process analytical technology (PAT) to crystallization processes. A description is provided of in-situ sensors including ATR-FTIR and Raman spectroscopies, laser backscattering, and process video microscopy as well as the use of the sensors and automation for the design of the operating procedures for batch and semibatch crystallization processes to produce crystals of desired size and polymorphic form. Industrial applications to antisolvent crystallization are described, as well as later applications to various polymorphic and pseudo-polymorphic crystallizations. The presentation summarizes techniques that have developed to simulate the effects of nonideal mixing for large-scale crystallizers, to guide the modification of bench-scale crystallization recipes to increase process reliability during scaleup. The talk ends with a description of recent innovations in using high-throughput microfluidic platforms for identifying the kinetic parameters needed in the simulation of nonideal mixing in crystallization.