Effect of Two Kinds of Supersaturation on Crystal Qualities during Cocrystallization

Cocrystals have attracted attention in the pharmaceutical field as a novel crystal form of solid drug substances. Crystalline particles with desired quality are required for practical use in industry. For the control of crystal qualities, supersaturation is the key. The supersaturation of cocrystal can be generated by an operation decreasing solubility such as anti-solvent addition or cooling as conventional crystallization of single component crystal. Moreover, the supersaturation of cocrystal also can be generated by the reaction of cocrystalline components. In this study, the effects of supersaturation including the viewpoint of supersaturation generation mechanisms are investigated. In the experiments, supersaturation was generated by using the two mechanisms in various distribution ratios in order to investigate the effect of the kinds of supersaturation during cocrystallization. The aspect ratios of obtained crystals were different by the distribution. There was a relationship between the aspect ratio and supersaturation ratio. The relationship was confirmed by an additional semi-batch experiment changing supersaturation generation speed. The aspect ratio distribution becomes narrower and average aspect ratio becomes smaller when the supersaturation generation speed was changed to be slower. Supersaturation ratio affects the shape of cocrystalline particles, while there are two kinds of supersaturation during cocrystallization.