Tuning membrane properties to control supersaturation of antisolvent crystallization

Abstract

The crystal morphology influences the properties of organic compounds, especially in pharmaceutics such as the dissolution and absorption of drugs in the human cells. In antisolvent crystallization, the crystal size and shape are tied to the degree of mixing and dosage of antisolvent, which could be controlled using membranes with specific morphology/surface properties. Little is known though on the relationship between membrane characteristics, antisolvent mass transfer and crystal properties. Flat sheet polyvinylidene fluoride (PVDF) membranes were prepared using non-solvent induced phase separation, to illustrate the impact of membrane characteristics on the resulting crystal size distribution (CSD) obtained using membrane-assisted antisolvent crystallization (MAAC). The crystallization of glycine was taken as case study. We showed the antisolvent transmembrane flux increased when the membrane thickness decreased, or when the hydrophobicity or the porosity increased. After MAAC operation, membranes had no significant change in surface functional groups, hydrophobicity nor structure. The best-performing membrane was found to have 119° hydrophobicity, 89.4 % porosity and 140 μm thickness, reaching high reproducibility of CSD corresponding to stable transmembrane fluxes throughout 180 min of operation. The capacity of MAAC to consistently produce a narrow CSD at optimum membrane characteristics makes this technology very competitive with conventional crystallization processes.