Understanding of the Solubility Curve in Solid–Liquid Equilibria

Solubility acts as an adjusting factor by linking the fugacity of the solid to the activity coefficient of the solute in the liquid phase. Therefore, in order to understand this important experimental information, the role of the solid through the fugacity of the solid phase and the role of the solvent through the activity coefficient in the liquid solution should be understood. This work is arranged to make a better picture of the current knowledge of the solubility curve in general and in particular for three different Active Pharmaceutical Ingredients (API’s) (salicylic acid, salicylamide, and fenofibrate) as examples. The behavior of the solubility curve at the two limiting extremes: the pure melt at the upper end and the infinitely dilute saturated solution of the solute in a particular solvent at the low end. Extending the solubility curve toward the subzero temperatures, as well as considering the solid fugacity equation as a whole, enables us to investigate these boundary conditions. Solution calorimetry data are combined with solubility data to examine in more detail the behavior of the solution activity coefficient. The results show that enthalpies of solution differ from the so-called van’t Hoff enthalpies of solution, and under most conditions, the influence of the activity coefficients cannot be neglected. The results also show that the heat capacity term in the solid phase fugacity equation plays an important role and should not be neglected. Having this information at hand may help to construct a more realistic model equation for the solubility curve of different systems.