Use of isothermal microcalorimetry in pharmaceutical preformulation studies, Part I. Monitoring crystalline phase transitions
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Solid-state transformation kinetics of two crystal forms of a synthetic tetrapeptide was monitored by isothermal microcalorimetry and complementary solid-state analytical techniques. Form B, the crystal form obtained from the synthetic process transformed to Form D upon exposure to higher relative humidity conditions (>60% RH). The transformation occurred rapidly at higher temperature, and relative humidities. An intermediate phase of very low crystallinity (amorphous-like phase) was observed when transformation was slow. Form D was observed to be physically stable at higher relative humidities and thus the preferred crystal form for development. Exposure of Form B to high relative humidity was the only process through which Form D was obtained. Optimal conditions for transformation of Form B to Form D were determined by microcalorimetric experiments and were used for larger scale processing of Form B to Form D.
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