Mixing Effect on Stoichiometric Diversity in Benzoic Acid–Sodium Benzoate Cocrystals

The aim of this study was to investigate the mixing effect on the stoichiometric diversity of benzoic acid–sodium benzoate (HBz–NaBz) cocrystals. The crystallization of HBz–NaBz cocrystals in a 500 mL sized glass vessel was monitored under different agitation speeds and feeding rates of HCl aqueous solution. Under good micromixing and macromixing, the HBz crystals, 2:1 and 1:1 cocrystals of HBz–NaBz were crystallized out rapidly, and all crystals were transformed to a mixture of 2:1 and 1:1 cocrystals of HBz–NaBz in a relatively short amount of time. However, the crystallization of 1:1 cocrystals of HBz–NaBz was delayed by poor micro-, meso-, and macromixing simultaneously. The compositions of the products were altered in different mixing conditions even given the identical experiment time. It was feasible to harvest pure 1:1 or pure 2:1 cocrystals of HBz–NaBz by reaction crystallization through the control of the mixing condition, concentration of reactants, and experiment time. The ternary phase diagram was also constructed for the HBz–NaBz–water system