Measurement and comprehensive analysis of the solubility of abacavir in twelve pure solvents

The solubility of abacavir in twelve pure solvents (methanol, ethanol, n-propanol, i-propanol, n-butanol, 2-butanol, i-butanol, n-pentanol, water, methyl acetate, ethyl acetate and acetone) was measured by high-performance liquid chromatography (HPLC) at the temperature range of (278.15 to 323.15) K under 101.1 kPa. In the temperature range studied, the solubility of abacavir in selected solvents increased with the rising temperature and the solubility sequence of abacavir at 298.15 K was n-pentanol > n-propa nol > 2-butanol > n-butanol > i-butanol > methanol > ethanol > i-propanol > acetone > methyl acetate > ethyl acetate > water. To explain the dissolution behavior of abacavir, the molecular electrostatic potential (MEP) and solvation free energy of abacavir were analyzed by density functional theory (DFT), while the Hansen solubility parameters and KAT-LSER model were introduced to analyze the molecular similarity and the solvent effect, respectively. In addition, three semi-empirical models (modified Apelblat equation, van't Hoff equation and lambda h equation) and three local composition models (Wilson equation, NRTL equation and UNIQUAC equation) were used to correlate the experimental solubility data of abacavir, and four indicators of relative deviation (RD), average relative deviation (ARD), root-mean-square deviation (RMSD) and coefficient of determination (R-2) were introduced to evaluate the correlated data. The results showed that the modified Apelblat equation had the highest accuracy among the semiempirical models; the NRTL equation was the most representative among the local composition models and had the best goodness-of-fit among all the solubility models. Furthermore, the mixing thermodynamic properties (Delta(mix)G, Delta H-mix and Delta S-mix) estimated by NRTL equation indicated that the mixing process of abacavir in selected solvents was spontaneous, exothermic and driven by enthalpy. (C) 2021 Elsevier B.V. All rights reserved.