Abstract
Purpose. To show that thermally stimulated depolarization currents (TSDC), which is a dielectric experimental technique relatively unknown in the pharmaceutical scientists community, is a powerful technique to study molecular mobility in pharmaceutical solids, below their glass transition temperature (Tg). Indomethacin (Tg = 42°C) is used as a model compound.
Methods. TSDC is used to isolate the individual modes of motion present in indomethacin, in the temperature range between −165°C and +60°C. From the experimental output of the TSDC experiments, the kinetic parameters associated with the different relaxational modes of motion were obtained, which allowed a detailed characterization of the distribution of relaxation times of the complex relaxations observed in indomethacin.
Results. Two different relaxational processes were detected and characterized: the glass transition relaxation, or α-process, and a sub-Tg relaxation, or secondary process. The lower temperature secondary process presents a very low intensity, a very low activation energy, and a very low degree of cooperativity. The fragility index (Angell's scale) of indomethacin obtained from TSDC data is m = 64, which can be compared with other values reported in the literature and obtained from other experimental techniques.
Conclusions. TSDC data indicate that indomethacin is a relatively strong glass former (fragility similar to glycerol but lower than sorbitol, trehalose, and sucrose). The high-resolution power of the TSDC technique is illustrated by the fact that it detected and characterized the secondary relaxation in indomethacin, which was not possible by other techniques.
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Correia, N.T., Moura Ramos, J.J., Descamps, M. et al. Molecular Mobility and Fragility in Indomethacin: A Thermally Stimulated Depolarization Current Study. Pharm Res 18, 1767–1774 (2001). https://doi.org/10.1023/A:1013339017070
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DOI: https://doi.org/10.1023/A:1013339017070