Bisacodyl in aqueous co-solvent solutions of isopropanol/methanol/ethanol: Solubility modeling, preferential solvation and density functional theory study

Abstract

At the microscopic level, quantitative analysis of molecular surface was used to highlight the electrostatic properties of acidity/basicity of bisacodyl. The -C = O and -N = groups are the principal targets of electrophilic attack because they have the lowest global electrostatic potentials, ranging from −157.6 kJmol−1 to −144.8 kJmol−1. The Hirshfeld partition analysis-based independent gradient model was used to visually examine the weak interactions between bisacodyl and the solvents, including methanol, ethanol, isopropanol, and water. The isothermal shake-flask method was used to evaluate the bisacodyl solubility in three aqueous co-solvent blends of isopropanol, methanol, and ethanol, under 101.2 kPa. The solubility data of bisacodyl in neat methanol is increased from 5.507 to 44.86 to 10-4 when the temperature rose from 278.15 to 323.15 K, whereas it climbed from 1.134 to 17.94 to 10-4 in neat isopropanol. The solubility variation is mostly caused by solvent–solvent interactions, which are explained by the solubility parameter, and solute–solvent interactions, which are explained by the dipolarity-polarizability of the solute. Three models—the Jouyban-Acree model, the modified van't Hoff-Jouyban-Acree-model, and the modified Wilson model were used to analyze the connection between solubility and experimental temperature and cosolvent composition, producing the largest relative average deviation of 9.41%. At temperatures between 293.15 K and 313.15 K, the preferred solvation of bisacodyl was examined using a method based on inverse Kirkwood-Buff integrals. The preferred solvation parameters of bisacodyl had positive values in the medium and rich concentrations of isopropanol/NMP (taken from a published work)/methanol/ethanol, suggesting that bisacodyl was preferentially solvated by these solvents. A quartic polynomial formulation of the interaction term as a function of the Hildebrand solubility parameter using an EHSA was used to accurately describe the solubility of bisacodyl in the four solutions. The dissolution of bisacodyl was entropy-driven process in all solvent mixtures.