Controlled antisolvent crystallization of miconazole nitrate in microfluidic droplets

Abstract

This study investigates the microfluidic-assisted antisolvent crystallization of miconazole nitrate (MCN). Droplets containing MCN dissolved in dimethyl sulfoxide (DMSO) and water were generated in a microfluidic device. As MCN is insoluble in water, it crystallized within the droplets as DMSO and water mixed. The droplets were formed in a flow focusing structure within a continuous phase. Two distinct crystal morphologies were observed: branched polycrystals and needle-like monocrystals. The firsts resulted from secondary nucleation under high supersaturation and migrated to the interface and into the continuous phase. The seconds originated from primary nucleation at a later stage, under lower supersaturation, and remained within the droplet’s bulk. Both types of crystals were characterized and compared to those produced under bulk industrial conditions. The study also examined the influence of droplet dimensions, flow rates, and solvent/antisolvent ratios. Additionally, internal vortices within the droplets were highlighted by observing the crystal motion during crystallization.