PHENOMENOLOGY OF POLYMORPHISM .3. P,T DIAGRAM AND STABILITY OF PIRACETAM POLYMORPHS

The nootropic drug Piracetam is known to crystallize in three phases. In order to obtain their stability hierarchy from sublimation pressure inequalities, the drawing of a topological p,T diagram was attempted. For such a purpose and also for quality control, crystallographic and thermodynamic data were required. Powder X-ray diffractometry (XRD) a nd differential scanning calorimetry (DSC) were used. Molecular energy calculations were performed. Phase I melts at 426 K (Delta(fus)H(I) = +180 J . g(-1)). Phase II transforms into Phase I at 399 K (Delta((II -->I))H = +24 J . g(-1)). Phase III transforms into phase I at 392 K ( Delta((III-->I))H = +28 J . g(-1)) or melts at 412 K (Delta(fus)H(III) = +210 J . g(-1)). The p,T diagram shows that phase I is stable at hi gher temperature and phase II at lower temperature, like phase III, wh ich is stable under high pressure. At room temperature, phase II is th e more stable form, and phase I the less stable one. This agrees with the spontaneous I --> II transformation observed at 298 K within a few hours, and with lattice energies, calculated previously. Molecular en ergy calculations and crystal structure comparison show how intermolec ular hydrogen bonds and H-bonded dimers, in phases II and III, may sta bilize conformations higher in energy than those of the isolated molec ule and of phase I. (C) 1996 Academic Press, Inc.