Role of Mechanical Stress in Crystallization and Relaxation Behavior of Amorphous Indomethacin

Even within an amorphous state, high energy sites can be generated due to sample handling and variations in preparation techniques can result in variation in these high energy sites. Such small handling variations may result in changes in physical properties and physical stability. The aim of this work is to characterize the differences in crystallization tendencies of amorphous Indomethacin arising from minor variations in sample handling. Amorphous Indomethacin was prepared by three variations on melt quenching using liquid nitrogen. Crystallization was studied by annealing the samples at various temperatures above Tg and then using DSC to observe the melt of the polymorph crystallized during annealing. The “No stress” samples showed only Tg whereas other samples showed three events: Tg, crystallization and melting. Even at high temperatures (90°C), crystallization was not reproducible in the “No Stress” sample. However, crystallization at 90°C was reproducible and immediate in samples with mechanical stress. At lower temperatures, differences were observed in extent of crystallization and in polymorph formed, which demonstrated the introduction of nuclei due to sample handling. Differences were also observed in relaxation kinetics of the different sample preparations. However, at 35°C the relaxation kinetics were similar but with crystallization behavior being different.