Controlling solid form and crystal habit of triphenylmethanol by antisolvent crystallization in a microfluidic device

Crystal habit and crystal form are critical elements in determining product properties and functions. In this work, we developed a microfluidic antisolvent crystallization technique to rapidly screen and accurately control the solid form and crystal habit of triphenylmethanol (Ph3COH). This advanced technique separates the primary mixing of solutions from crystal formation (nucleation and growth) by introducing the microfluidic device, avoiding clogging in microchannels to obtain high-quality crystals. The results show that we can achieve controllable preparation of pure 2Ph3COH·DMSO (DMSO solvate), pure Ph3COH (form β), and mixed crystals with different mass ratios. Moreover, the microscale can prompt the DMSO solvate to grow into hexagonal sheet-like and bulk crystals. We can regulate the aspect ratio of hexagonal sheet-like crystals in binary solvents and control the crystal habit of the form β to transition between long needle-like shapes and short hexagonal prisms in DMF-H2O. Meanwhile, we revealed that the solvent ratio, the antisolvent flow rate, and the initial concentration of Ph3COH are the main factors affecting the solid form selectivity and morphology transition. Such a novel method would be considered as a promising technique to be extended to screen and control key crystallization parameters of other substances.