Investigation on the Hansen solubility parameter, solvent effect and thermodynamic analysis of indapamide dissolution and molecular dynamics simulation

Abstract

In this work, the dissolution behavior of indapamide (IDP) in different solvents was researched. Solubility of IDP in methanol, ethanol, acetonitrile, 1-propanol, ethyl acetate, 2-propanol, 2-butanone, acetone, toluene and cyclohexane at series temperatures (278.15 K-318.15 K) was determined. The outcomes indicated that the solubility of IDP increased with increasing temperature. At a certain temperature, the mole solubility sequence of IDP was acetone > 2-butanone > methanol > ethanol > 1-propanol > acetonitrile > 2-propanol > ethyl acetate > toluene > cyclohexane. The Hansen solubility parameter (HSP) was used to evaluate ability of solvent to dissolve and explain the solubility behavior of IDP. Solvent effect was discussed by Kamlet and Taft linear solvation energy relationship (KAT-LSER) model, and the hydrogen bonds interactions (HBA) and nonspecific dipolarity/polarizability interactions had more advantageous impact on solubility of IDP. Moreover, molecular dynamics (MD) simulation was employed to construct the dissolving model and provide molecular level understanding the solute–solvent interaction in dissolution process of IDP. In addition, the experimental solubility data of IDP was correlated by Apelblat model, λh model, NRTL model and Wilson model. The applicability of these models were evaluated by Akaike Information Criterion analysis. The relative average deviation (RAD) and root-mean-square deviation (RMSD) values were no greater than 2.94% and 5.03 × 10−4, respectively. These four thermodynamic models were able to correlate the solubility data well and the Apelblat model was the best correlation model of these four models. Finally, the dissolution thermodynamic properties were obtained by van't Hoff analysis. The all positive values of thermodynamic properties indicated that the dissolution of IDP was an endothermic and entropy driven process.