(424a) Enhancing Process Understanding and Control with Real-Time Analytics for a Challenging Solid Form System of a Pharmaceutical Compound

In the recent years, process analytical technology (PAT) has been widely used on the pharmaceutical development and manufacturing for better process understanding and control. For example, the information of the in-situ particle size distribution by Particle Track (Lasentec ® FBRM) is invaluable on the crystallization development and scale-up. This paper discussed a case of solid state development of a drug candidate that has high tendency to form solvates in most process solvent systems. The only feasible pathway to produce the desired non-solvated form was through a slurry conversion after adjusting the solvent composition through solvent swap distillation. Multiple PAT tools have been evaluated for process understanding and in-line monitoring of a form conversion process, for example, 1) the use of PVM to monitor the conversion of morphology, 2) the use of the FTIR to monitor the progress of de-solvation 3) the use of the combination of Particle Track and Raman for solid form control.