Continuous Antisolvent Crystallization of Carbamazepine Dihydrate: Experiments and Modeling

Abstract

Continuous antisolvent crystallization of carbamazepine dihydrate was carried out in three crystallizers, namely, stirred tank, oscillatory baffle crystallizer, and fluidic oscillator (with a helical coil). A generalized population balance model is developed using a tanks-in-series framework. Options for providing multiple input locations and internal recycling have been implemented. The crystallization kinetics were estimated by fitting the experimentally measured particle-size distributions and concentration profiles. The model was able to describe the continuous crystallization experiments reasonably well for all of the crystallizers considered in this work. The feed supersaturation was found to influence the yield of the process by a 10% increase on increasing the feed supersaturation from 1.5 to 4.5. The residence time was found to influence both the particle-size distribution and the overall yield of the process (increasing the residence time from 12 to 24 min, increased the yield by 10% and the particle size by 55 μm). Under the same operating conditions, the yield in the oscillator baffled crystallizer and the fluidic oscillator surpassed that of the stirred tank crystallizers by approximately 10%. The presented model and results will provide a sound basis for further work on the optimization of the crystallization of carbamazepine.