Temperature-dependent solubility of Rebaudioside A in methanol/ethanol and ethyl acetate mixtures: Experimental measurements and thermodynamic modeling

The equilibrium solubility of Rebaudioside A (Reb A) Form II in binary mixtures of methanol/ethanol and ethyl acetate was quantitatively determined within the temperature range of 283.15 to 328.15 K at ambient pressure. The experimental findings indicate a positive correlation between the solubility of Reb A (Form II) and both the temperature and the methanol/ethanol content in the solvent system. To describe the solubility data, six distinct models were employed: the modified Apelblat equation, the λh model, the CNIBS/R-K model, the van't Hoff-Jouyban-Acree (VJA) model, the Apelblat-Jouyban-Acree (AJA) model, and the Non-Random Two-Liquid (NRTL) model. The CNIBS/R-K model exhibited the most precise fit for solubility in methanol+ethyl acetate mixtures, reflected by an Average Relative Deviation (ARD) of 0.0011 and a Root Mean Square Deviation (RMSD) of 0.0000012. Conversely, for ethanol+ethyl acetate mixtures, the modified Apelblat equation provided a superior correlation (ARD=0.0014, RMSD=0.0000004). Furthermore, thermodynamic parameters associated with the dissolution of Reb A (Form II), including enthalpy, entropy, and the Gibbs energy change, were inferred from the data. The findings underscore that the dissolution process is predominantly endothermic across the solvent systems examined. Notably, the entropy changes appear to have a significant influence on the Gibbs free energy associated with the dissolution of Reb A (Form II), suggesting that entropic factors may play a pivotal role in the studied systems.