Particle Size Control in Batch Crystallization of Pyrazinamide on Different Scales

A methodology to achieve consistent particle size in seeded batch crystallization on two scales (0.5 and 10 L) was demonstrated using pyrazinamide as a model compound. An empirical process model was established from a Design of Experiment study on the 500 mL scale and subsequently verified by correlating D-50 of the crystals with stirrer speed, seed size, and seed loading. Experiments on the 10 L scale showed that the criterion of equivalent impeller tip speed produced a larger D-50 than that of equivalent input energy. The process model derived from the 0.5 L scale was demonstrated to work well for process parameter adjustment to obtain the target product size on the 10 L scale. Some practical issues in crystallization development are discussed.