Investigation of the Dissolution Behavior of Diludine in Monosolvents: Solid–Liquid Equilibrium Determination, Model Correlation, and Thermodynamic Analysis

Abstract

Diludine and its derivatives are important precursors widely employed in the design and synthesis of dihydropyridine calcium channel blocker (CCB) drugs. The solid–liquid-phase equilibrium data and dissolution properties of diludine can provide fundamental thermodynamic data for the synthesis, separation, and further study of CCBs in the industry as well as the academic arena. The solubility of diludine in 16 pure solvents, including eight alcohols, three ketones, three esters, toluene, and acetonitrile from 272.15 to 323.65 K under atmospheric pressure, was measured using the gravimetric method. The solid–liquid equilibrium curve of diludine indicated an increasing trend with an increase in the temperature. The solvent polarity is a critical factor influencing the solubility behavior, but it is not the only one. Four thermodynamic models (i.e., the modified Apelblat model, λh model, NRTL model, and Wilson model) were used to correlate the solubility data. The Wilson model showed the most satisfactory agreement. Furthermore, the dissolution thermodynamic properties (Δ_disS, Δ_disH, and Δ_disG) of diludine in selected solvents were estimated on the basis of thermodynamic relations and the regressed Wilson model.