Compatibility study between diazepam and tablet excipients: Infrared spectroscopy and thermal analysis in accelerated stability conditions

Compatibility between diazepam (DZP), a benzodiazepine drug used for the treatment of anxiety, and tablet excipients has been investigated by thermal analysis (differential scanning calorimetry—DSC and thermogravimetry—TG) and infrared (IR) spectroscopy. In order to investigate possible interactions, the components were prepared in 1:1 (w/w) mixtures. Moreover, individual samples as well as physical mixtures were stored in accelerated conditions at 40 °C/75 % RH for 3 months. Mixtures, which showed possible interactions, were also investigated in other ratios based on typical pharmaceutical solid formulation. DSC curves of DZP have shown an endothermic peak at 132 °C, which corresponds to the melting process in agreement with the literature. DSC curves of the mixtures containing DZP and colloidal silicon dioxide (CSD) indicated a possible interaction due to enthalpy values lower than expected. However, as this interaction was not confirmed by IR and TG, this suggests that these techniques are not sensitive enough to identify such interaction. These results suggest that there is a possible interaction, but not an incompatibility between DZP and CSD. For all other mixtures, it was not possible to identify significant interactions, suggesting that there are no compatibility issues.