Measurement and modeling correlation of capecitabine solubility in n-hexane + ethyl acetate and n-heptane + ethyl acetate at various temperatures

Abstract

In this work, by using laser dynamic isothermal method, the solubilization behavior and thermodynamics of capecitabine solubility in the binary mixtures of n-hexane + ethyl acetate and n-heptane + ethyl acetate from (278.15 to 323.15) K were measured under atmospheric pressure. The measured results showed that the experimental solubility of capecitabine increased non-linearly with increasing temperature and ethyl acetate content (w1) in the studied mixture solvents. Six cosolvency mathematical models including the modified Apelblat equation, combined nearly ideal binary solvent/Redlich-Kister (CNIBS/R-K) equation, Wilson model, non-random two liquid (NRTL) model, UNIQUAC model, and the modified Jouyban-Acree-van't Hoff model were fitted to the experimental results. The maximum relative average deviation (ARD) was 0.27, the maximum root-mean-square deviation (RMSD) was 0.0007. The order of the relative average deviation (ARD) of the six cosolvency mathematical models is CNIBS/R-K > modified Jouyban-Acree-van't Hoff > NRTL > Wilson > modified Apelblat > UNIQUAC. Basically speaking, the measured solubility data in this study can be well correlated with the six thermodynamic models, while the modified Jouyban-Acree-van't Hoff model allowed the calculation of solubility of capecitabine at an arbitrary mixture composition and temperature in the studied binary solvent mixtures composition and temperature. Moreover, apparent thermodynamic properties of capecitabine dissolution process in the investigated mixed solvents including entropy, enthalpy and Gibbs free energy were computed using van't Hoff and Gibbs equations. Besides, the logarithm of activity coefficient of capecitabine (lnγ1) in the studied saturated solutions were also calculated with the NRTL model, UNIQUAC model, and Wilson model, respectively. The positive values of lnγ1 means that the repulsive interactions exist between capecitabine and the corresponding mixture solvents, and the solutions system positively deviate from Raoult's law. This work can give fundamental data for the crystallization and purification of capecitabine from ethyl acetate.