Impact of membrane characteristics on anti-solvent crystallization

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

Finer drug production has been an ongoing concern by pharmaceutical industries. The latter has been incorporating advances at different levels; for example, artificial intelligence was used to select compounds for drug formulation, robotics was implemented to reduce the heavy labor loading, etc. Anti-solvent membrane-assisted crystallization can be the next revolutionary intervention within the downstream processing of active pharmaceutical ingredients (APIs). Amino acids’ crystallization is then investigated to verify the potential of this technology. Membrane-assisted crystallization not only controls the crystal characteristics but also minimizes the amount of anti-solvent used; two important features that are lacking in conventional crystallizers. In this work, aqueous solutions containing L-serine reached supersaturation with the controlled addition of the antisolvent through the membrane pores. The crystallization performance is assessed by determining the resulting crystal shape, size distribution, and growth rate. A series of polyvinylidene fluoride (PVDF) membranes are developed and characterized in terms of hydrophobicity/philicity, roughness, pore size, porosity, and thickness. The impact of PVDF membrane characteristics on the crystallization of the amino acid is discussed, which is a first in the literature. The increase of transmembrane flux, with larger pore size and lower thickness, accelerates crystal growth rate. Eventually, the impact of membrane characteristics on the crystallization offers a fundamental understanding that supports the use of this technology in the quest of controlling different API-related aspects such as polymorphism, chirality, and purity.