Abstract
The solubility values of polyphenolic compounds in different extraction solvents are crucial for their recovery from natural matrices. Hansen solubility parameters (HSPs) stand out as a predictive tool for evaluating solute-solvent affinity and thus rational solvent selection for extraction processes. In this study, HSPs of trans-resveratrol and hesperetin were calculated using a semi-empirical method to assess the capability to predict the solubility behavior of both polyphenols in organic binary solvent mixtures. Experimental solubility of both polyphenols was determined in up to 21 monosolvents at 298.15 K and 0.1 MPa and used to classify them to iteratively calculate HSPs. Calculated HSPs were compared and discussed with literature values in terms of molecular interactions, demonstrating a fair agreement. Solubility of trans-resveratrol and hesperetin was then determined in methanol + MEK, ethanol + MEK, methanol + MiBK, ethanol + MiBK, and methanol + ethanol binary solvent mixtures. trans-Resveratrol achieved higher mole fraction solubility than hesperetin in all binary mixtures across the whole molar fraction range except in methanol + MiBK. Both compounds exhibited enhanced solubility in all alcohols + ketone binary mixtures, attributed to synergistic solvent effects. HSP analysis revealed a minimum Hansen distance between solute and solvent mixtures at compositions corresponding to the solubility maximum in synergistic systems. Additionally, calculated HSPs proved to effectively estimate the concentration at which this phenomenon occurs in all tested systems, reaching a robust correlation between maximum solubility and minimum Hansen distance. Overall, insights from this study underscore the effectiveness of experimentally derived HSPs in predicting the solubility behavior of polyphenols and seek to provide valuable guidance on solvent selection strategies for the recovery of bioactive compounds.