(189bo) Refining the Nonrandom Two-Liquid Segment Activity Coefficient Model By Applying the Association Theory

Much interest has recently been devoted to accurately correlating and predicting drug solubility (Tanveer, S., et al., Chem. Eng. Prog. 2014, 110 (9), 37-47). Solubility models like the Non-Random Two Liquid Segment Activity Coefficient (NRTL-SAC) model (Chen, C.-C., and Song, Y., Ind. & Eng. Chem. Res. 2004, 43 (26), 8354-8362) are now routinely used in the pharmaceutical industry. However, this model does not explicitly account for specific intermolecular interactions such as hydrogen bonding. In this study, we refine the NRTL-SAC model by including an association term of activity coefficient, which is based on Wertheim’s association theory. Additionally, we reduce the number of conceptual segments to two to represent polar and nonpolar surface characteristics of molecules. We also define two types of association sites to represent the hydrogen bond donor and hydrogen bond acceptor, respectively: molecules have both types of sites self-associate; molecules containing one type of sites can only cross-associate with molecules containing the other type of sites. The refined model generally performs better than the original model for various phase equilibrium calculations, especially for systems containing hydrogen bonds. The correlation and prediction of drug solubility are also improved by the refined NRTL-SAC model.