Crystal nucleation and growth of indomethacin polymorphs from the amorphous state

The effect of temperature on the overall crystallization, and the crystal nucleation and growth rates of indomethacin polymorphs from the amorphous state were determined. Crystallization of amorphous indomethacin at temperatures close to or below its Tg (42°C) favors the formation of the stable γ polymorphic form, while crystallization at higher temperatures favors the formation of the metastable α-crystal form. Both the nucleation and growth rates for γ-indomethacin have maxima that coincide just above the Tg of amorphous indomethacin. The nucleation rate for α-indomethacin was found to have a maximum at 60°C, and the growth rate at 90°C. Assuming a temperature dependent crystal–amorphous interface free energy, good agreement was observed between the experimental nucleation data and the predictions of the classical theory of nucleation. The crystal–amorphous interface energy was higher for the γ than for the α-indomethacin. Analysis of the crystal growth rates for both crystal forms showed that the mechanism of growth is by two-dimensional nucleation, but quantitative agreement with the theory was not found. The interface energy for the α-crystal form, obtained from the growth data was in very good agreement with the value obtained from the nucleation data.