Solubility of melatonin in ethyl acetate + (N, N-dimethylformamide, 2-methoxyethanol, 2-ethoxyethanol and methanol): Determination, correlation, thermodynamic properties and Hansen solubility parameter at saturation

Abstract

For further study on solubility behaviors of melatonin (MT), the solubility of MT in the three mono-solvents {N, N-dimethylformamide (DMF), 2-methoxyethanol, 2-ethoxyethanol} and four binary solvents {(DMF, 2-methoxyethanol, 2-ethoxyethanol and methanol) + ethyl acetate} was measured in a range of 278.15 K–323.15 K by laser monitoring method. The measurement results showed that MT solubility in all tested solvents increased with rising temperature. In binary solvents except methanol + ethyl acetate, the solubility values of MT had a positive relationship with the mass fraction of co-solvents. In methanol + ethyl acetate, the solubility of MT initially increased, followed by a decrease (with the rising mass fraction of methanol) and arrived the highest solubility value at a mass fraction of methanol being 0.4000. The Hansen solubility parameters (HSPs) were applied to study the solubility behaviors of MT in tested solvents. Moreover, in three pure solvents, the measured solubility data of MT was correlated by (NRTL-SAC, NRTL, two-Suffix Margules, UNIQUAC models and modified Apelblat equation). In binary solvents, the solubility data was fitted by (three-Suffix Margules, λh equation, Yaws model equation and modified Apelblat equation). Furthermore, the apparent thermodynamic properties were calculated based on the van’t Hoff equation. The positive values of apparent standard dissolution enthalpy and entropy suggest that the dissolution process of MT in all of chosen solvents is entropy-driven and endothermic. The larger values of ζH than ζTS represent that the main contributor of ΔdisGo in all investigated solvents is enthalpy.