Phase equilibrium behaviors of chiral threonine: Phase diagrams, solubility, and thermodynamic model correlations

Abstract

Phase equilibrium behaviors of chiral racemic threonine, as well as D-Threonine and L-Threonine, have been systematically investigated. The PXRD patterns, DSC, and ternary phase diagram exhibited the typical characteristics of the conglomerate. As an essential basis for ternary phase diagrams, the solubility of D-Threonine, L-Threonine, and the racemic mixture was measured at a temperature range from 283.15 K to 308.15 K in both water/methanol and water/ethanol mixtures. The solubility of a single enantiomer was at a range from 1.08 to 2.23 (S, wt%) in water/methanol = 6/4 v/v and from 0.36 to 0.91 (S, wt%) in water/methanol = 4/6 v/v. The racemate exhibited a double solubility of the single enantiomer. Subsequently, the experimental solubility data showed promising correlations with five thermodynamic models: Jouyban-Acree equation, Machatha model, the modified Apelblat model, Wilson model, and NRTL model. The modified Apelblat model was the best-fit model when the temperature was primarily considered. Whereas Jouyban-Acree model demonstrated better alignment when the solvent composition was mainly regarded. Besides the above approaches for the determination of chiral drug systems, the results were analyzed in the different characteristics between the racemate and the single pure enantiomer. Selecting the appropriate model to correlate with solubility data can facilitate the exploration of the ternary phase diagram of chiral drugs under different conditions, thus favoring the subsequent enantiomeric separation and industrial production.