Solution Mediated Polymorphic Transformation: Form II to Form III Piracetam in Ethanol

The polymorphic transformation of the Piracetam (2-oxo-1-pyrrolidine acetamide) metastable form II to the stable form III has been investigated in ethanol, by ex-situ X-ray diffraction analysis of the solid phase combined with in situ infrared analysis of solution concentrations. The main factors studied were temperature, mass of solids loading, and pretreatment of the loaded solids. At increasing temperature, the solubility ratio decreases and, hence, the transformation driving force decreases. In spite of this, the nucleation induction time of the stable form and the time for completion of the transformation decrease with increasing temperature. The transformation rate is governed by the nucleation and growth of the stable form, with nucleation likely to take place on the faces of the metastable form crystals and the rate increasing with surface area of the metastable form.