Experimental and Modeling Assessment of Polyphenol Solubility in Alcohol + Ethyl Acetate Mixtures for Extraction Applications

Abstract Polyphenols are valuable bioactive compounds widely used in the pharmaceutical and cosmetic industries, yet their extraction is often limited by low solubility in conventional solvents. This work extends the solubility database of four polyphenols (trans-polydatin, p-coumaric acid, quercetin, and trans-resveratrol) by determining and modeling their equilibrium solubility in methanol, ethanol, and ethyl acetate at 298.2 K and 0.1 MPa. Additionally, solubility in two binary mixtures (methanol + ethyl acetate and ethanol + ethyl acetate) was measured to assess the ester cosolvent effect. Excess solubility was calculated to evaluate nonideality, and experimental data were correlated using the Abraham solvation model, the CNIBS/R–K equation, and solvatochromic (KAT) parameters. Higher solubility was observed in ethanol than methanol for all compounds except for trans-polydatin, while ethyl acetate showed the lowest values. All ternary systems exhibited solubility maxima due to synergistic effect of ethyl acetate, being the greatest solubility enhancement observed for trans-resveratrol, with a 129% increase at 0.4 mole fraction of the ester solvent in the methanol + ethyl acetate binary solvent mixture. Eventually, all systems were accurately described by the Abraham model, CNIBS/R-K equation, and KAT parameters.