Surface crystallization of indomethacin below Tg

Purpose To study the surface crystallization of indomethacin (IMC) below T _g and its effects on the kinetics of overall crystallization.Methods Crystal growth rates in liquid layers formed between microscope cover glasses were measured with the top cover glass in place and removed. Polymorphs were identified by powder X-ray diffraction, Raman microscopy, and melting-point determination by hot-stage microscopy. Surface crystals were identified by scratching the sample surface, by cutting the sample to expose its interior, and by analyzing the intensity of X-ray diffraction. Amorphous IMC particles of different sizes were stored at 40°C (T _g−2°C) and analyzed at different times by differential scanning calorimetry to obtain the kinetics of crystallization.Results Crystal growth of IMC below T _g at the free surface was approximately two orders of magnitude faster than that in the bulk, resulting in a surface layer of crystals around a slower-crystallizing interior. Surface crystallization yielded mainly the γ polymorph. Amorphous IMC powders showed rapid initial crystallization at 40°C, but the crystallization abruptly slowed down at “saturation levels” below 100%; the larger the particles, the lower the “saturation level.”Conclusion The faster surface crystallization of IMC than the bulk crystallization leads to unusual crystallization kinetics wherein a rapid initial increase of crystallinity is followed by an abrupt slowdown of crystallization. Surface crystallization should be distinguished from bulk crystallization in modeling and controlling the crystallization of amorphous solids.