Solution thermodynamics of acetaminophen in some PEG 400 + water mixtures

According to the van’t Hoff and Gibbs equations, the thermodynamic functions Gibbs energy, enthalpy, and entropy of solution of acetaminophen (ACP) in some PEG 400 + water mixtures were evaluated from drug solubility values determined at several temperatures. By using values of the thermodynamic properties of fusion and sublimation of ACP, the thermodynamic quantities of mixing and solvation were also calculated. By means of enthalpy–entropy compensation analysis, a non-linear ΔsolnH° vs. ΔsolnG° compensation plot with negative and positive slopes was obtained considering the entire composition interval, indicating entropy-driving in water-rich mixtures and enthalpy-driving in PEG 400-rich mixtures.

► The acetaminophen solubility was maximal in pure PEG 400 and minimal in pure water.
► Thermodynamic quantities of solution, mixing, and solvation were obtained for acetaminophen.
► A non-linear plot of ΔsolnH° vs. ΔsolnG° compensation is found for acetaminophen at 303.0 K.