Crystallization kinetics and glass-forming ability of rapidly crystallizing drugs studied by Fast Scanning Calorimetry

The use of the amorphous forms of drugs is a modern approach for the enhancement of bioavailability. At the same time, the high cooling rate needed to obtain the metastable amorphous state often prevents its investigation using conventional laboratory methods such as differential scanning calorimetry, X-ray powder diffractometry. One of the ways to overcome this problem may be the application of Fast Scanning Calorimetry. This method allows direct determination of the critical cooling rate of the melt and kinetic parameters of the crystallization for bad glass formers. In the present work, the amorphous states of dopamine hydrochloride and atenolol were created using Fast Scanning Calorimetry for the first time. Critical cooling rates and glass transition temperatures of these drugs were determined. Based on the values of the kinetic fragility parameter, dopamine hydrochloride glass can be considered strong, while atenolol glass is moderately strong. Both model-based and model-free approaches were employed to determine the kinetic parameters of cold crystallization of dopamine and atenolol. The results were compared with the data from isothermal crystallization experiments. The Nakamura crystallization model provides the best description of the crystallization process and can be used to predict the long term stability of the amorphous forms of the drugs. The presented approaches may find applications in predicting the storage time and choosing the optimal storage conditions of the amorphous drugs prone to crystallization.

Automated summary

The use of amorphous forms of drugs is a modern approach to enhance bioavailability. Fast Scanning Calorimetry was applied to create amorphous states of dopamine hydrochloride and atenolol for the first time, determining critical cooling rates and glass transition temperatures. The Nakamura crystallization model provided the best description of the crystallization process, useful for predicting the long term stability of the drugs' amorphous forms.