(762f) Estimating NRTL-SAC Conceptual Segments of Molecules Using Sigma Profile

The Non-Random Two Liquid Segment Activity Coefficient (NRTL-SAC) model¹ as a solubility model is now routinely used in the industry^2-3. In this model, the conceptual segments are defined to describe molecular surface characteristics, i.e., hydrophobicity, hydrophilicity, polarity. In practice, the conceptual segments of molecules must be identified from experimental phase equilibrium data with other solvents, and that limits the model applicability to molecules with sufficient phase equilibrium data. In this work, a methodology is presented to estimate the conceptual segments from the sigma profile, which is the molecular surface charge density distribution calculated from computational quantum chemistry, and is used in COSMO-based models^4-5. We present the rationale and algorithm of segment numbers estimation from sigma profiles. Therefore, the applicability of NRTL-SAC model can be expanded to any components with known structures. The predicted phase equilibria, e.g., VLE, LLE, SLE, are compared with experimental data and predictions from other activity coefficient models to validate the model performance. The proposed approach allows the NRTL-SAC model to predict solubility in unconventional solvents, excipients, or polymers, where phase equilibrium data are insufficient to identify their segment numbers.

1. Chen, C.-C.; Song, Y., Solubility modeling with a nonrandom two-liquid segment activity coefficient model. Industrial & Engineering Chemistry Research 2004, 43 (26), 8354-8362.

2. Gani, R.; Jiménez-González, C.; ten Kate, A.; Crafts, P. A.; Jones, M.; Powell, L.; Atherton, J. H.; Cordiner, J. L., A modern approach to solvent selection. Chemical Engineering 2006, 113 (3), 30-43.

3. Tung, H. H.; Tabora, J.; Variankaval, N.; Bakken, D.; Chen, C. C., Prediction of pharmaceutical solubility Via NRTL‐SAC and COSMO‐SAC. Journal of Pharmaceutical Sciences 2008, 97 (5), 1813-1820.

4. Klamt, A., Conductor-like screening model for real solvents: a new approach to the quantitative calculation of solvation phenomena. The Journal of Physical Chemistry 1995, 99 (7), 2224-2235.

5. Lin, S.-T.; Sandler, S. I., A priori phase equilibrium prediction from a segment contribution solvation model. Industrial & Engineering Chemistry Research 2002, 41 (5), 899-913.