Enhanced thermal stability of carbamazepine obtained by fast heating, hydration and re-crystallization from organic solvent solutions: A DSC and HPLC study

Although drugs are usually stored at room temperature, their thermal stability up to the melting point is often required for processing such as quenching or hot-melt extrusion. It especially concerns substances which have poor water solubility, as these techniques are used to either assess the glass forming ability or to prepare solid dispersions with the aim to enhance dissolution rate and bioavailability. Carbamazepine (CBZ), an antiepileptic drug, is an example of active pharmaceutical ingredient which shows both limited solubility in water and decomposition below melting point. This paper suggests and discusses different ways to enhance CBZ thermal stability, namely fast heating of the sample, hydration and re-crystallization from organic solvents (ethanol, acetone and dichloromethane). The presence of a model degradation product, i.e. iminostilbene is evaluated using differential scanning calorimetry and high-performance liquid chromatography. Obtained results show that all three proposed approaches are able to reduce the degree of CBZ thermal degradation, however none of them entirely stops the decomposition of CBZ in the vicinity of the melting point.