Solubility of flavonoids in pure and mixed solvents

Flavonoids are receiving considerable attention due to their important biological and pharmacological properties [1]. In particular, the systematic study of their solubility in liquid solvents is being presented in the literature [2-8] to support the design of extraction, precipitation or crystallization processes. These compounds have a complex structure with a variety of functional groups that makes them difficult to represent by traditional thermodynamic models. This work is divided in two parts. In the experimental section, new solubility data is presented for hesperetin in several pure and mixed solvents at different temperatures. The shake-flask method is applied, followed by quantitative analysis. Concerning the thermodynamic modelling section, it presents the results obtained using the NRTL-SAC model [9,10], in combination with the reference solvent approach (RSA) [11,12], to describe the solid-liquid equilibrium of several flavonoids in pure and mixed solvents. The NRTL-SAC model represents molecules by conceptual segments: hydrophobic, polar attractive or repulsive and hydrophilic. For each solute, four parameters are calculated using experimental solubility data in a selected set of solvents that should, preferably, cover a wide range of molecular interactions. Additionally, the application of the RSA approach avoids the knowledge of the thermal properties that are often unknown for flavonoids. Finally, the excess solubility approach (ESA) [13-15] with one parameter correlative model is also applied to describe the solubility in mixed solvents