Investigation of the solid-state polymorphic transformations of piracetam

The solid-state polymorphic transformations of 2-oxo-1-pyrrolidine acetamide (piracetam) were investigated using a combination of off-line and online techniques: differential scanning calorimetry (DSC), high temperature X-ray diffraction (HT-XRD), thermal analysis, and hot-stage optical microscopy. Form II and Form III were each observed to transform directly to Form I upon heating, with Form II transforming at a slightly lower temperature. The transformation of both polymorphs to Form I was observed to cause physical cracking of the crystals as well as changing the optical properties. Form I consistently transformed to Form II when cooled. The molecular rearrangements required for the transformation from Form I to Form II were found to be more energetically favorable than those required for the transformation to Form III. The transformation from the metastable Form II to the stable Form III was not observed in the solid-state, while the Form II-Form III transition temperature was found to be higher than the transition temperature of both polymorphs to Form I.