Solid-liquid equilibrium of glucosamine hydrochloride in four binary solvents: Experiments, modeling, and molecular simulation

Abstract

Glucosamine hydrochloride (GAH) is a marine biological preparation derived from natural chitin and improves articular cartilage metabolism. In this study, the solubility of GAH in four binary solvents (water + methanol, water + ethanol, water + isopropanol, and water + acetone) was gravimetrically determined over the temperature range of 283.15 K to 323.15 K. The solubility of GAH were found increasing monotonically with water content and temperature. In alcohol mixtures, the solubility of GAH can be ranked as: (water + methanol) > (water + ethanol) > (water + isopropanol). Four thermodynamic models (the modified Apelblat equation, van't Hoff equation, (CNIBS)/R-K model and Jouyban-Acree model) were used to correlate the experimental solubility data, which the (CNIBS)/R-K model showed the best fitting performance. The dissolution thermodynamic properties of GAH were also calculated. The results indicate that the dissolution process is driven by both entropy and enthalpy. To explore the solid–liquid equilibrium behavior from molecular level, the Hirshfeld surface of GAH crystal was generated and molecular dynamics simulations of mixed systems were performed. Based on equilibrium configurations of different mixtures, molecular interactions between solvent–solvent and solute–solvent were calculated. Meanwhile, the simulation snapshots and radial distribution function plots were analyzed to interpret association of solvents.