Molecular mobility and fragility in indomethacin: a thermally stimulated depolarization current study.
OBJECTIVE
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 degrees 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 degrees C and +60 degrees 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 alpha-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.
Correia
N T
NT
Centro de Química-Física Molecular, Lisboa, Portugal.
Ramos
J J
JJ
Descamps
M
M
Collins
G
G
D002151:Calorimetry; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D007213:Indomethacin / Q000737:chemistry*; D008956:Models, Chemical; D015394:Molecular Structure; D013696:Temperature
D007213:Indomethacin