Isothermal Crystallization Monitoring and Time-Temperature-Transformation of Amorphous GDC-0276 and nifedipine: Differential Scanning Calorimetric and Rheological measurements

Cold crystallization is an important topic in understanding the stability of amorphous pharmaceutical ingredients (API). In the present work, the isothermal crystallization of amorphous pharmaceutical compounds GDC0276 and nifedipine are monitored by two different screening techniques: differential scanning calorimetric and rheometric measurements. For both techniques, the classic Avrami equation was applied to describe the isothermal crystallization kinetics from the induction to the completion period, and the time-temperature-transformation diagrams were constructed for induction and completion time points of crystallization. The temperature dependence of viscosity was obtained from the rheological measurement and used to estimate the kinetic term in a modified classic nucleation and crystal growth model, which is further fitted to the temperature dependence of the crystal induction and completion times. The modification assumed is that the kinetics follow the viscosity to the 0.75 power as suggested by recent work. From the crystallization kinetics modeling, the solid-liquid interfacial energy was determined and compared with that obtained from melting point depression measurements. The differences between the values from the two methods are discussed.