Membrane-assisted antisolvent crystallization: a gateway to control particle formation

Chergaoui, Sara [UCL] Debecker, Damien P. [UCL] Leyssens, Tom [UCL] Luis Alconero, Patricia [UCL]

Crystallization is present in separation and purification processes particularly for the selection of organic molecular compounds as in pharmaceutical and food sectors. The crystal shape and crystal size distribution (CSD) dictates the final product end use and quality, hence the control of these physical properties is crucial to avoid any cumbersome downstream processing. The potential of membrane-assisted antisolvent crystallization (MAAC) is demonstrated in this work for the control of antisolvent mass transport and mixing responsible for final crystal quality. The evolution of crystallizing solution and antisolvent composition along the operation time of MAAC was established to understand the transmembrane mass transport behavior responsible for the resulting crystallization dynamics, using hydrophobic Polypropylene (PP) and Polyvinylidene fluoride (PVDF) membranes. Besides, PVDF membranes tailored with various thicknesses, hydrophobicity and porosity were developed to unravel how membrane properties control crystallization. The amino acid crystallization via ethanol addition was specifically chosen as it is representative typical antisolvent crystallization systems, placing this work in the wider context of antisolvent crystallization. The increase of the antisolvent or the crystallizing solution velocities did not necessarily increase the antisolvent transmembrane flux as previously reported in [1]; instead, it has proven that an excess of one or another at a specific spacetime inside the membrane module can result in wetting or the system blockage, originating from the membrane, module, or tubing. Besides, decreasing membrane thickness, increasing hydrophobicity and increasing porosity resulted in a higher transmembrane flux of antisolvent, a shorter induction time and smaller crystals. Most importantly, for all the studied conditions, the CSD was much narrower than that of commercially available glycine without any compromise with the crystal purity. This study invites us to use the principles of mass transfer in porous membranes to describe and gain an understanding of the resulting crystal quality produced.