Determination and modelling of density, viscosity and solubility of (R)-(-)-phenylephrine hydrochloride in methanol + ethyl acetate at (278.15–323.15) K and 0.1 MPa

Abstract

For further optimizing the pipeline design of continuous crystallizer, in this research work, density, viscosity and solid-liquid equilibria (SLE) solubility of (R)-(-)-phenylephrine hydrochloride (R-PEC) in binary solvent of “methanol (MtOH) + ethyl acetate (EtAC)” were investigated at temperature T = (278.15–323.15) K under pressure p = 0.1 MPa. The results showed that experimental density and viscosity values were negatively related with temperature while the SLE solubility data had positive correlation with the experimental temperature. Moreover, density and viscosity profiles increased with the incremental molarity of R-PEC, similarly, solubility of R-PEC raised along with the mass fraction of MtOH in binary solvents. Hansen solubility parameter (HSP) was applied to investigate the solubility behavior of R-PEC in MtOH+EtAC, four selected solubility parameters could give a logical explanation on R-PEC solubility. By using Mathcad software (Version: 15), the Vogel-Tammann-Fulcher (VTF) equation was employed for the description of density as well as viscosity values. Values of average relative deviation (ARD), multi-correlation coefficient (R2) and root-mean square deviation (RMSD) between experimental data and predicted data showed that VTF equation could provide satisfactory correlations with the experimental data. Besides, solubility values of R-PEHC in selected binary solvent were correlated with three activity coefficient models including Wilson, NRTL (Non-Random Two Liquids) and UNIQUAC (Universal Quasi–Chemical) model by using Mathcad software, the UNIQUAC model were more suitable for correlation with experimental solubility than others in terms of ARD and RMSD. Furthermore, based on the experimental solubility results and regression parameters of UNIQUAC model, thermodynamic properties of mixing and dissolution process were discussed in this work, the results showed that the both processes of R-PEHC in MtOH+EtAC were always spontaneous and entropy driven, the mixing process and part of dissolution process (R-PEHC in MtOH + EtAC at T ≤ 303.15 K) were exothermic. Experimental densities, viscosities, solubility as well as selected models would be very helpful for optimizing the pipeline design (including material selection, size calculation and so on) of continuous crystallizer.