Background The experimental measurement of the solubility of a solute in a given solvent is a difficult task, hence the need of reliable thermodynamic models for its prediction. However, these models require either molecular or group interaction parameters which are not always available. Objective The objective of the present study is to measure experimentally the solubility of different solutes in solvents selected from pharmaceutical or food fields, on the basis that not all the required model interaction parameters are available to use the obtained experimental data for their determination. Method The experimental study of solid-liquid equilibrium for chosen binary and ternary systems at different temperatures was carried out using the Differential Scanning Calorimetry to determine the essential thermo physical properties like melting temperature and enthalpy. The modeling of these phase equilibrium data was performed by means of thermodynamic models like Random Two Liquids (NRTL) and Universal Functional Activity Coefficient (UNIFAC). The required NRTL interaction parameters were determined by minimizing a well-defined objective function, using the simplex method. Results The solubilities of the solutes in the different considered solvents at different temperatures obtained experimentally provided the required NRTL molecular interaction parameters. Solute solubilities were obtained by means of NRTL, UNIFAC, and ideal models. The comparisons showed an excellent agreement between the experimental values and the NRTL results, contrary to UNIFAC and ideal case models. Conclusion This study shows the importance of thermodynamic modeling to predict solubility data that may be difficult, time consuming, and costly to obtain experimentally.