Caffeic acid is a phenolic compound found in several plants and fruits including coffee beans. It has high nutraceutical value because of antioxidant activity. Its advantageous effects have been recognized in cancer, diabetes, Alzheimer, cardiovascular and inflammatory diseases. It has low aqueous solubility which can be enhanced by complexation with natural CDs according to AL type isotherms . The association constants are 1512, 390 and 297 M-1 for α-, β- and γCD, respectively.
The solubility in water-ethanol mixture is increased exponentially with increasing ethanol content.
The combined effect of complexation and cosolvent resulted in U-shape curves with minima at 5-15% (v/v) ethanol for the CD concentration of 5, 7.5 and 10 mM . As the medium became more apolar due to the presence of ethanol, the concentration of free caffeic acid increased and the solubilizing effect of CDs decreased, also the association constants decreased. At 45% (v/v) ethanol the solubility of caffeic acid remained unaltered by adding CD. The result is explained by the weakening of the driving force (the decreasing difference in polarity between the CD cavity and the medium). The results were justified by NMR studies and by assessment of the antioxidant activity.
Similar results on the effect of ethanol on inclusion complex formation was obtained for fluasterone complexation with HPBCD  and piroxicam encapsulation with β- and γCD and dimethyl βCD  in ethanol-water mixtures with increasing ethanol concentration.
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