Thermodynamic analysis of solubility, distribution and solvation of antifungal miconazole in relevant pharmaceutical media

Abstract

In this work, solubility of antifungal drug miconazole in pharmaceutically relevant solvents were measured by the shake-flask method in the temperature range between 293.15 and 313.15 K. The solubility of compound in selected solvents increases in the following order: buffer pH 7.4, buffer pH 2.0, hexane, 1-octanol. The influence of protolytic properties of the drug on the solubility in aqueous media of different acidity was studied. It is shown that the modified Apelblat equation give better correlation results with the experimental data than Hoff equation and Two-Suffix Margules model. The Hansen solubility parameters were employed to investigation the miscibility of compound with all of tested solvents. The calculation of the thermodynamic functions of drug solubility and solvation in the selected solvents was performed. The relative contributions of sublimation and solvation to Gibbs energy of solubility for the compound in used solvents was evaluated. The excess Gibbs energy and the activity coefficients of miconazole were also calculated. The temperature dependence of the partition coefficients of the compound studied in the 1-octanol/buffer pH 7.4 system was determined and thermodynamic quantities for the transfer of this drug from water phase to organic one were obtained.