Key interactions between membrane and antisolvent crystallization system: experimental and MD simulations

Chergaoui, Sara [UCL] Tocci, Elena [CNR-ITM] Debecker, Damien P. [UCL] Leyssens, Tom [UCL] Luis Alconero, Patricia [UCL]

Membrane-assisted antisolvent crystallization (MAAC) is an emerging technology that can control antisolvent crystallization and give a crystal size distribution up to four times narrower than conventional batch crystallization. Nonetheless, little is understood regarding the interactions between the different compounds of the system, i.e., the solvent, antisolvent, solute and membranes, so molecular dynamics (MD) simulations were conducted to understand the key interactions responsible for the control of crystal formation. Models for MD simulations were developed to study the differences in molecular interactions while transitioning from an undersaturated system (S=0.74) to supersaturated systems (S=1.35 and 2.39). A model consists of a dense PVDF layer and a solution mixture at its surface, as illustrated in Figure 1. All models were run under an ambient temperature of 300 K for 500ns using Gromacs software. A difference in the diffusion induced difference in the organization of glycine molecules. Empirically, Polyvinylidene fluoride (PVDF) membranes were developed with various thicknesses, porosities and hydrophobicities to investigate the key membrane properties that impact crystallization. Glycine in water was used as crystallizing solution, and pure ethanol as an antisolvent. For membrane thickness, the coefficient of variation (CV) of the crystal size distribution (CSD) improved from 22, 18 to 16%, corresponding to the thicknesses of 70, 100 and 140 μm (Figure 2). As for membrane hydrophobicity and porosity, the impact was not as significant, although a narrow CSD was observed in the entire range, i.e., membrane contact angles of 99-119° and porosities of 83 to 89%. These findings were explained with supersaturation evolution and the antisolvent mass transfer, evaluated throughout experimental operation. This fundamental understanding motivates future steps in using this technology to control different aspects of antisolvent crystallization, such as the crystal size of heat-sensitive compounds.