Solubility equilibria in chiral systems and their importance for enantioseparation

Ternary solubility equilibria are studied for three chiral systems in various aqueous and nonaqueous solvents. The chosen systems were a pharmaceutical intermediate, threonine and mandelic acid. Measured solubility data are presented and the nature of the ternary solubility phase diagrams is described. On this basis possible procedures for a crystallization based enantioseparation are derived. Also, the impact of solubility equilibria on the resolution of racemates by liquid chromatography is analyzed and discussed for the systems under investigation. Finally, a hybrid approach coupling both separation techniques for an efficient chiral resolution is demonstrated by means of the fundamental solubility phase diagrams. © 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei