Crystal nucleation and growth of indomethacin polymorphs from the amorphous state

The effect of temperature on the overall crystallization, and the crystal n ucleation and growth rates of indomethacin polymorphs from the amorphous st ate were determined. Crystallization of amorphous indomethacin at temperatu res close to or below its T-g (42 degrees C) favors the formation of the st able gamma polymorphic form, while crystallization at higher temperatures f avors the formation of the metastable alpha-crystal form. Both the nucleati on and growth rates for gamma-indomethacin have maxima that coincide just a bove the T-g of amorphous indomethacin. The nucleation rate for alpha-indom ethacin 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 nucleati on data and the predictions of the classical theory of nucleation. The crys tal-amorphous interface energy was higher for the gamma than for the alpha- indomethacin. Analysis of the crystal growth rates for both crystal forms s howed that the mechanism of growth is by two-dimensional nucleation, but qu antitative agreement with the theory was not found. The interface energy fo r the alpha-crystal form, obtained from the growth data was in very good ag reement with the value obtained from the nucleation data. (C) 2000 Elsevier Science B.V. All rights reserved.