Comparison of amorphous states prepared by melt-quenching and cryomilling polymorphs of carbamazepine

The physical state of amorphous powder obtained by cryomilling forms I and III of carbamazepine (CBZ) were analyzed from low-wavenumber Raman spectroscopy investigations and compared to that of the quenched liquid. This analysis has shown subtle structural modifications between the amorphous states prepared by melt-quenching and cryomilling polymorphs I and III of CBZ. Moreover, two different non-isothermal crystallization mechanisms from these two different types of amorphous states were revealed, in agreement with calorimetric analyzes. Raman spectroscopy and differential scanning calorimetry experiments performed on cryomilled forms I and III of CBZ, provide information on the bimodal crystallization, observed upon heating several amorphous organic crystalline materials produced by milling. This study clearly shows that milling gives the opportunity to explore new amorphous states which cannot be achieved using the classical melt-quenching method.