Solubility and conversion of carbamazepine polymorphs in supercritical carbon dioxide

The aim of this work was to investigate whether mixtures of carbamazepine polymorphs could be processed in supercritical (SC) CO 2 in order to obtain the pure stable crystalline phase. To accomplish this goal the solubility of carbamazepine polymorphs I and III in supercritical CO 2 was first assessed using a low solvent flux dynamic method. Mixtures of Form I and Form III were processed in dynamic or static conditions in SC-CO 2. Differential scanning calorimetry, Fourier transformed infrared spectroscopy, and powder X-ray diffractometry were used to analyse solid samples in terms of polymorph composition. It was found that Form I and Form III of carbamazepine have different solubility in supercritical CO 2 at 55°C above 300 bar. Due to the transformation of the metastable form, conversion of Form I into Form III can be carried out on a binary mixture of the two polymorphs by treating the mixture at 55°C and 350 bar, under both static and dynamic conditions, via its solubilization in supercritical CO 2.