Intelligent Automated Parallel Crystallization Platform for Crystalline Drug Development

An intelligent automated high-throughput parallel crystallization platform is designed, which includes multiple (>6) stirred tank reactors. Each crystallizer is equipped with temperature measurement and a turbidity meter, which can intelligently and automatically measure drug solubility and crystallization metastable zone, as well as screen crystal forms. The solubility measurement values of carbamazepine in ethanol are compared with the solubility data determined by gravimetric method and literature data, and the results are satisfactory. The solubility data are fitted using Modified Apelblat model, quadratic polynomial model, and three parameter van't Hoff models. The platform is also used to measure the metastable zone of carbamazepine crystallization in ethanol, providing reference for crystallographic research and application. Finally, the cooling crystallization system is used to screen crystal polymorphic forms by changing the solvent, initial solution concentration, cooling rate, stirring rate, crystal seeds, and other conditions. X-ray powder diffraction (PXRD) analysis and characterization reveal that three types of carbamazepine polymorphic forms and dihydrates are finally obtained.