Solubility Prediction of Active Pharmaceutical Compounds with the UNIFAC Model
The crystallization from solution of an active pharmaceutical ingredient requires the knowledge of the solubility in the entire temperature range investigated during the process. However, during the development of a new active ingredient, these data are missing. Its experimental determination is possible, but tedious. UNIFAC Group contribution method Fredenslund et al. (Vapor liquid equilibria using UNIFAC: a group contribution method, 1977; AIChE J 21:1086, 1975) can be used to predict this physical property. Several modifications on this model have been proposed since its development in 1977, modified UNIFAC of Dortmund Weidlich et al. (Ind Eng Chem Res 26:1372, 1987) Gmehling et al. (Ind Eng Chem Res 32:178, 1993) Pharma modified UNIFAC Diedrichs et al. (Evaluation und Erweiterung thermodynamischer Modelle zur Vorhersage von Wirkstoffloslichkeiten, PhD Thesis, 2010) KT UNIFAC Kang et al. (Ind Eng Chem Res 41:3260, 2002) \ldots In this study, we used UNIFAC model by considering the linear temperature dependence of interaction parameters as in Pharma modified UNIFAC and structural groups as defined by KT UNIFAC first order model. More than 100 binary datasets were involved in the estimation of interaction parameters. These new parameters were then used to calculate activity coefficient and solubility of some molecules in various solvents at different temperatures. The model gives better results than those from the original UNIFAC and shows good agreement between the experimental solubility and the calculated one.