Elucidation of the Kinetic Behavior of Quercetin, Isoquercitrin, and Rutin Solubility by Physicochemical and Thermodynamic Investigations
Résumé
The solubility of flavonoids in organic media is a complex and important process. It is a key factor in extraction, formulation, and biocatalysis processes of flavonoids. In this work, dissolution experiments showed that the solubility of quercetin, isoquercitrin, and rutin in tert-amyl alcohol is higher (20, 30, and 36 g/L) than in acetonitrile (1.7 g/L). Moreover, dissolution kinetic of quercetin in tert-amyl alcohol showed an unusual behavior of the amount dissolved over time. High concentrations of dissolved quercetin were measured at the beginning of the experiment. The maximum concentration was followed by a decrease later on in time until the saturation concentration was obtained. To explain these results, thermodynamic (enthalpy of dissolution and mixing) and physicochemical (microscopy, particle size measurement) experiments were carried out. The enthalpies of dissolution (Delta H-diss) and mixing (Delta H-mix), measured in this work, are consistent with the experimental solubility scale for quercetin and rutin, i.e. rutin/tert-amyl alcohol < isoquercitrin/tert-amyl alcohol < quercetin/tert-amyl alcohol < quercetin/acetonitrile, with values ranging from ca. 12 to 180 J/g and -123 to 43 J/g, respectively. Microscopic observations and particle size measurement showed an increase of quercetin particles size, in tert-amyl alcohol, throughout the dissolution process (0.4 and 8 mu m at 5 min, 14-60 mu m after 68 min of dissolution). This surprising behavior, in contrast to the experience in common dissolution experiments (quercetin, isoquercitrin, and rutin in acetonitrile, isoquercitin and rutin in tert-amyl alcohol), has never been observed for flavonoids and is called kinetic size effect.