Towards a PAT-Based Strategy for Crystallization Development

A strategy for the rapid, material-efficient development of crystallization processes centred around the use of process analytical technology (PAT) is presented and demonstrated on an active pharmaceutical ingredient (API) currently in development at Pfizer's Sandwich laboratories. PAT is implemented at scales as small as 1 mL in high-throughput equipment, enabling the early acquisition of key data to select the best crystallization approach. At a larger scale, PAT offers a window into process kinetics and, for the case study discussed in this contribution, highlighted vulnerabilities of the process arising from the formation of a labile solvate. A combination of on-line and off-line analyses provided the basis for a full assessment of the process.