Solubility is a fundamental parameter in the discovery of new drug molecules as well as in their production using crystallization processes. In this work, we experimentally investigate the solubility in different solvents and the density of the anti-cough drug guaifenesin and characterize its solid state via Powder X-Ray Diffraction (PXRD) and thermal analysis. Moreover, a strategy is developed and successfully applied to predict the density and solubility behavior of that pharmaceutical. On the solubility curve concentration and temperature depend on each other for a binary solution at fixed pressure. Therefore, densities of undersaturated aqueous solutions of guaifenesin are measured and used alongside with solubility data to obtain more realistic parameters of thermodynamic model. Perturbed Chain-Statistical Associating Fluid Theory (PC-SAFT) Equation of State (EoS) is used. It was able to successfully represent the solubility curves using a small amount of data for fitting the model parameters. In a second part, the applicability of the model to predict the solubility in various organic solvents of two other pharmaceutically relevant molecules, namely the anti-inflammatory drug ketoprofen and the antimalarial compound artemisinin has been studied.

The results showed that guaifenesin is the most soluble in ethanol and least soluble in ethyl acetate. Its aqueous solubility shows a special behavior with a specific sharp increase with temperature. In all of the solvents, ketoprofen is the highest soluble among the compounds studied followed by guaifenesin and artemisinin. PC-SAFT is able to capture the experimentally observed effects of temperature, and solvent type on the solubility behavior of each of the three solutes.