Thermodynamics of complex formation between hydroxypropyl-β-cyclodextrin and quercetin in water–ethanol solvents at T = 298.15 K

Quercetin (QCT) is a flavonoid possessing many activities, such as neuro-/cardioprotective, anti-inflammatory and anticancer, but its pharmacological application is severely curtailed by its low water solubility and in vivo bioavailability. The formation of a QCT-hydroxypropyl-b-cyclodextrin (HPbCD) host-guest complex is promising to improve QCT therapeutic potential. Therefore, here the heat effects of HPbCD solutions with QCT solutions in water-ethanol solvents at different concentrations were studied by calorimetric titration, and the stability of molecular complexes was assessed by UV-Vis spectrophotometry. Calorimetric titrations revealed the formation of a QCT/HPbCD host-guest complex with a stoichiometric ratio of 1:1 in X(EtOH) = 0.00, 0.05 and 0.10 molar fractions of solvents at pH = 7.0 and pH = 8.1. Thermodynamic parameters of the complex formation reaction (lgK; Delta H-r; T Delta S-r) were obtained in these experimental conditions. Differently, no complex formation was noticed in water-ethanol mixed solvent when ethanol volume fraction exceeded 0.2 at neutral and alkaline pH, as well as a volume fraction higher than 0.1 at acidic pH. Furthermore, the results of differential scanning calorimetry tests run on dried HP beta CD after dissolution in hydroalcoholic solutions indicated that ethanol and water compete for the complexation within the hydrophobic cavity of HP beta CD. This explains the decreased QCT complexation efficacy in the presence of ethanol beyond 0.1 or 0.2 volume fraction.