The interaction between quercetin (QUE) \(/\) 7-hydroxy flavone (7-HF) and nicotinamide (NAM) in drug formulations is an intriguing area of research due to their complementary biological effects. When used together, their combined actions can potentially offer synergistic therapeutic benefits. The objective of the present study is to analyze and interpret the types of interactions among various polar, non-polar, hydrophilic and hydrophobic parts of quaternary systems (QUE + water \(+\text{ethanol}\) + NAM) and (7-HF + water \(+\text{ethanol}\) + NAM) by volumetric and acoustic approach. The positive values of \({\text{V}}_{\upphi }^{0}\) exhibit an increasing trend with temperature, indicating that there is a significant solute–solvent interaction in the investigated solutions. Positive partial molar expansibilities demonstrate that QUE/7-HF promotes solute–solvent interactions in the system and functions as a structure former in aqueous solutions. The partial isentropic compressibility, \({\text{K}}_{\text{s}}^{0}\) values are higher in 7-HF than in QUE showing greater extent of molecular interactions in 7-HF. From the derived data, the types of solute–solvent and solute–solute interactions and the structural modifications of water molecules were interpreted as a result of the inclusion of QUE/7-HF (solute) and NAM (co-solute) in the solvation shells. This study may provide a better understanding regarding the stronger solute–solvent interactions and structure-building ability of QUE/7-HF + NAM in a hydro-ethanolic medium, which may further help develop a pharmaceutical formulation of their mixture.
