Antisolvent Crystallization and Polymorph Screening of Glycine in Microfluidic Channels Using Hydrodynamic Focusing

Extensive screening of the polymorph and solvate space of a given active pharmaceutical ingredient molecule is an important step in early-stage pharmaceutical product development. Thus, a significant need exists in the pharmaceutical industry for experimental techniques that facilitate the screening process with minimal material consumption and effort. Here we describe an experimental technique that facilitates antisolvent crystallization in a microfluidic channel using diffusive mixing of solutions at laminar flow interfaces (hydrodynamic flow focusing). This setup is able to produce complex and localized concentration gradients of solute and antisolvent in the microchannel, which in turn trigger the selective formation of α- and β-glycine crystals in a water-2-propanol solvent system. We correlate the polymorph selectivity observed to an empirical parameter that characterizes the supersaturation gradients. Our experiments demonstrate that characteristics of physics at the micrometer scale can be leveraged to influence the polymorph formation and habit modification of molecular crystals. (Figure Presented)