期刊
ORGANIC PROCESS RESEARCH & DEVELOPMENT
卷 20, 期 12, 页码 2100-2107出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.oprd.6b00327
关键词
particle size control; scale-up; batch crystallization; empirical process model; operational variability; seeding
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.
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