Pressure-temperature state diagram for the phase relationships between benfluorex hydrochloride forms I and II: A case of enantiotropic behavior

The active pharmaceutical ingredient racemic benfluorex hydrochloride (benfluorexHCl) has an interesting phase behavior due to an elusive solidsolid phase transition. The stability hierarchy between different phases is often determined based on heat-related experiments only or slurry interconversion. It is shown that if pressure and volume are taken into account, not only the phase equilibria are correctly positioned in the pressuretemperature phase diagram, but the experimental data also improves. Thus, it has been found that the racemic benfluorexHCl is enantiotropic under ordinary conditions with polymorph II and polymorph I, respectively, being the low- and the high-temperature phases. Above similar to 151MPa, the system becomes monotropic and polymorph II is the single stable phase. (c) 2011 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:10731078, 2012