Enantiomeric 3-Chloromandelic Acid System: Binary Melting Point Phase Diagram, Ternary Solubility Phase Diagrams and Polymorphism

ABSTRACTA systematic study of binary melting point and ternary solubility phase diagrams of the enantiomeric 3-chloromandelic acid (3-ClMA) system was performed under consideration of polymorphism. The melting point phase diagram was measured by means of thermal analysis, that is, using heat-flux differential scanning calorimetry (DSC). The results reveal that 3-ClMA belongs to the racemic compound-forming systems. Polymorphism was found for both the enantiomer and the racemate as confirmed by X-ray powder diffraction analysis. The ternary solubility phase diagram of 3-ClMA in water was determined between 5 and 50°C by the classical isothermal technique. The solubilities of the pure enantiomers are extremely temperature- dependent. The solid-liquid equilibria of racemic 3-ClMA are not trivial due to the existence of polymorphism. The eutectic composition in the chiral system changes as a function of temperature. Further, solubility data in the alternative solvent toluene are also presented. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:4084–4095, 2010