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 T(g) (42 degrees C) favors the formation of the stable gamma polymorphic form, while crystallization at higher temperatures favors the formation of the metastable alpha-crystal form. Both the nucleation and growth rates for gamma-indomethacin have maxima that coincide just above the T(g) of amorphous indomethacin. The nucleation rate for alpha-indomethacin was found to have a maximum at 60 degrees C, and the growth rate at 90 degrees 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 gamma than for the alpha-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 alpha-crystal form, obtained from the growth data was in very good agreement with the value obtained from the nucleation data. (C) 2000 Elsevier Science B.V. All rights reserved.