Tailoring polyvinylidene fluoride membrane hydrophobicity, porosity and thickness to control α-Glycine antisolvent crystallization

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

Amino acids are small molecules that form the elementary basis of peptides and proteins crucial for life. They are synthetically produced using antisolvent crystallization resulting in random crystal size distribution (CSD). The control of kinetic and thermodynamic aspects such as rate of nucleation, growth and supersaturation is key to obtain a narrow CSD, saving further downstream processing [1]. The importance of tracking the evolution of crystallizing solution and antisolvent composition along the operation time was established in [2] to understand the transmembrane mass transport behavior responsible for the resulting crystallization dynamic. This study takes a step further by addressing the link between membrane characteristics of the hydrophobic polymeric membranes, polyvinylidene fluoride in this case, and the resulting crystal properties. Membranes were developed using non-solvent induced phase separation, with porosities of 0.83, 0.86 and 0.89, water contact angles of 99, 108 and 119° and thicknesses of 70, 100 and 140 µm, and evaluated according to their performance in membrane-assisted antisolvent crystallization (MAAC). The thinner was the membrane, the more hydrophobic or the more porous it was, the higher was the antisolvent transmembrane flux, the lower was the induction time and the smaller were the resulting crystals. Most importantly the CSD was much narrower compared with the commercially available Glycine, without any compromise with the crystal purity. This tendency was less apparent for crystals formed at the membrane surface, plus these crystals were slightly larger than those formed at the bulk solution. That is attributed to the difference in turbulence and antisolvent concentration between the bulk and solution at the membrane vicinity [3]. MAAC is indeed capable of intensifying crystallization processes by providing a one-step narrow crystal size distribution for example or potentially help in polymorph selection, purifying challenging reactions or developing thermally sensitive nanoparticles (active pharmaceutical ingredients, metal-organic frameworks ...).