Experimental determination and computational analysis of solid-liquid phase equilibrium of nifedipine in twelve pure solvents

Abstract Nifedipine is an oral calcium channel blocker in clinical practice, and widely used to prevent and treat heart diseases. In this work, the equilibrium solubility of nifedipine (NIF) in twelve pure solvents including alcohols and esters was determined by static method at temperatures ranging from 283.15 K to 323.15 K. In all studied solvent systems, the solubility increases monotonously with increasing temperature. Besides, the effect of solvent properties on solid–liquid phase equilibrium of NIF was investigated. The results show that the solubility of NIF correlates well with the solvent properties in alcohol solvents but no obvious correlation can be found in ester solvents. In addition, the solubility data was correlated with the modified Apelblat equation, λh equation, van't Hoff equation and NRTL model, and the overall fitting ARD% are 0.94%, 2.15%, 2.75% and 4.03% respectively. Therefore, the modified Apelblat equation achieves the best fitting performance. Furthermore, in order to quantitatively study how the solute–solvent interaction affects the solubility, the solvation free energy was calculated by the molecular dynamic (MD) simulation. The absolute values of solvation free energy of esters (−18.96 to −20.32 kJ·mol−1) are higher than those of alcohols (−15.21 to −17.54 kJ·mol−1), which is consistent with the order of solubility values. Moreover, COSMO-RS σ-profiles were employed to qualitatively describe the intermolecular interactions. Finally, the COSMO-RS model was employed to predict the solubility of NIF in the studied solvents. The results show a good performance on predicting the solubility of NIF though the deviations existed in some cases.