Solubility, thermodynamic properties and solute-solvent molecular interactions of luteolin in various pure solvents

Abstract

The objective of this study was to evaluate solubility, thermodynamic properties and solute-solvent molecular interactions of poorly water-soluble bioactive compound luteolin (LUT) in various pure solvents namely water (H2O), ethylene glycol (EG), propylene glycol (PG), polyethylene glycol-400 (PEG-400), methanol (MeOH), ethanol (EtOH), isopropanol (IPA), 1-butanol (1-BuOH), 2-butanol (2-BuOH), ethyl acetate (EA), dimethyl sulfoxide (DMSO) and Transcutol® (THP) at temperatures “T = 298.2 K to 318.2 K” and pressure “p = 0.1 MPa”. The solubility values of LUT at equilibrium were determined using a shake flask technique with the help of ultra-performance liquid chromatography technique at 348 nm. The solid state of LUT in pure and equilibrated form was characterized using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) techniques. The solubilities of LUT measured by shake flask method were correlated with “van't Hoff and Apelblat models”. The DSC and PXRD spectra of pure and equilibrated LUT were similar, suggesting no transformation of LUT during equilibrium. Good correlation was recorded between experimental and calculated solubilities of LUT. The solubility values of LUT (mole fraction) were obtained maximum in PEG-400 (1.27 × 10−1) followed by DMSO (7.15 × 10−2), THP (4.01 × 10−2), 2-BuOH (5.53 × 10−3), 1-BuOH (5.36 × 10−3), EA (5.11 × 10−3), IPA (4.14 × 10−3), PG (3.89 × 10−3), EtOH (3.08 × 10−3), EG (2.38 × 10−3), MeOH (8.16 × 10−4) and H2O (4.17 × 10−6) at “T = 318.2 K” and similar trend was obtained at each temperature studied. The physical values of activity coefficients were determined with the help of ideal solubilities of LUT. Based on the physical values of activity coefficients, maximum solute-solvent interactions were observed in LUT-PEG-400, LUT-DMSO and LUT-THP. Apparent thermodynamic analysis suggested endothermic and entropy-driven dissolution of LUT in each pure solvent studied.