TSDC and DSC Investigation on the Molecular Mobility in the Amorphous Solid State and in the Glass Transformation Region of Two Benzodiazepine Derivatives: Diazepam and Nordazepam.

In this work we study the molecular mobility in the amorphous solid state and in the glass transformation region of two compounds, diazepam and nordazepam; these are two benzodiazepines, a family of psychotropic drugs with sedative, anxiolytic and muscle-relaxing properties. The experimental techniques used are thermostimulated currents (TSC) and differential scanning calorimetry (DSC). TSC is a time-dependent technique recognized for its high resolving power; the use of this technique in the depolarization and polarization modes (TSDC and TSPC respectively), provides results that confirm and complement results of dielectric relaxation spectroscopy (DRS) published recently. On the other hand, the variation with the heating rate of the temperature position of the DSC glass transition signal also allowed the estimation of the activation energy at Tg and of the dynamic fragility of the two glass formers.

The slow relaxation dynamics in active pharmaceutical ingredients studied by DSC and TSDC: Voriconazole, miconazole and itraconazole.

The slow molecular mobility of three active pharmaceutical drugs (voriconazole, miconazole and itraconazole) has been studied by differential scanning calorimetry (DSC) and thermally stimulated depolarization currents (TSDC). This study yielded the main kinetic features of the secondary relaxations and of the main (glass transition) relaxation, in particular their distribution of relaxation times. The dynamic fragility of the three glass formers was determined from DSC data (using two different procedures) and from TSDC data. According to our results voriconazole behaves as a relatively strong liquid, while miconazole is moderately fragile and itraconazole is a very fragile liquid. There are no studies in this area published in the literature relating to voriconazole. Also not available in the literature is a slow mobility study by dielectric relaxation spectroscopy in the amorphous miconazole. Apart from that, the results obtained are in reasonable agreement with published works using different experimental techniques.

Estimation of the fragility index of indomethacin by DSC using the heating and cooling rate dependency of the glass transition.

In this study we have investigated the features of the glass transition relaxation of indomethacin using Differential Scanning Calorimetry (DSC). The purpose of this work is to provide an estimation of the activation energy at the glass transition temperature, as well as of the fragility index, of amorphous indomethacin from DSC data. To do so, the glass transition temperature region of amorphous indomethacin was characterized in both cooling and heating regimes. The activation energy for structural relaxation (directly related to glass fragility) was estimated from the heating and cooling rate dependence of the location of the DSC profile of the glass transition. The obtained results were similar in the heating and in the cooling modes. The results on the fragility index of indomethacin obtained in the present study, m = 60 in the cooling mode and m = 56 in the heating mode, are compared with other values previously published in the literature.

The activation energy at Tg and the fragility index of indomethacin, predicted from the influence of the heating rate on the temperature position and on the intensity of thermally stimulated depolarization current peak.

PURPOSE: The purpose of this study was to estimate the activation energy at the glass transition temperature (and the fragility index) of amorphous indomethacin from the influence of heating rate on the features of the relaxation peaks obtained by thermally stimulated depolarization currents (TSDC) and to compare the obtained results with those obtained by other procedures based on TSDC data. METHODS: The glass transition temperature region of amorphous indomethacin was characterized at different heating rates by TSDC in a way similar to that used to determine the kinetics of the glass transition relaxation by differential scanning calorimetry. The features of a thermal sampled TSDC peak, namely the temperature location and the intensity, depend on the heating rate. RESULTS: The activation energy for structural relaxation (directly related to glass fragility) was estimated from the heating rate dependence of the TSDC peak location, T(m), and of the maximum intensity of the TSDC peak, I(T(m)). CONCLUSIONS: The methods for determining the activation energy for structural relaxation and fragility of indomethacin from TSDC data obtained with different heating rates were compared with other procedures previously proposed. TSDC, which is not a very familiar technique in the community of pharmaceutical scientists, proved to be a very convenient technique to study molecular mobility and to determine the fragility index in glass-forming systems. The value of approximately 60 appears as a reasonable value of the fragility index of indomethacin.