Insights into the penetration of PhACs in TCM during ultrafiltration: Effects of fouling mechanisms and intermolecular interactions

[Display omitted] •The impact of PhACs on the BSA fouling mechanism was analyzed by the Hermia model.•The penetration mechanism of PhACs was investigated during ultrafiltration.•The transport of PhACs was affected by the fouling mechanisms and the intermolecular interactions.•Examination of intermolecular interactions through a combination of QCM-D and MD. The objective of this study was to understand the influence of membrane fouling on the penetration of pharmaceutically active compounds (PhACs) in traditional Chinese medicine (TCM). Four types of TCM PhACs (palmatine, berberine, geniposide, and protocatechuic acid) and three different concentrations of bovine serum albumin (BSA) were formulated into model solutions, to evaluate the researching penetration mechanisms of PhACs under membrane fouling conditions during a cross-flow ultrafiltration (UF) process. The Hermia model was applied to analyze the membrane fouling mechanisms, and quartz crystal microbalance with dissipation (QCM-D) monitoring and molecular dynamics (MD) simulations were used to analyze the intermolecular interactions between BSA and different TCM PhACs. The results confirmed that the presence of PhACs affected the fouling mechanisms. For example, the fouling models of 10.0 g/L BSA solutions changed from cake filtration to complete blocking in the presence of berberine. Under the condition of the membrane fouling, the penetration of PhACs was mainly affected by the intermolecular interactions. The penetrations of the four PhACs studied for all tested BSA solutions were consistent with the intermolecular interaction data obtained using QCM-D and MD simulations. According to the results of the MD simulations, the intermolecular interactions between BSA and palmatine and berberine (-42.99 and −79.16 kJ/mol) were more significant than those between BSA and geniposide and protocatechuic acid (-2.68 and −3.51 kJ/mol), making penetration of the alkaloids (palmatine and berberine) more difficult. The QCM-D results were similar. This study provides a better understanding of PhAC penetration during the UF of TCM solutions.