Characterization, thermal stability, and solid-state phase transition behaviors of gestodene polymorphs and amorphous phase

Abstract

In the current work, a systematic investigation on the thermal behavior of gestodene was carried out to understand temperature induced solid-state transitions between its polymorphs and amorphous phase. The focus was on polymorph identification, thermal stability analysis, and the nature of the phase transitions. These characteristics were compared to the complexity of the phase transitions, studied by differential scanning calorimetry (DSC) and variable temperature X-ray powder diffraction (VT-XRD) techniques. DSC studies indicated that the form II was enantiotropically related to form I, which melted at about 470 K. The temperature of polymorphic transition was 309 K, and form II was the more stable form between room temperature and the transition temperature. A schematic Gibbs free energy-temperature diagram was subsequently constructed to describe the thermal stability of the two forms. Amorphous phase converted exothermically to form I at 368 K on heating and was shown by VT-XRD to be accompanied by diffraction pattern changes. In addition, the crystallization kinetics studied by DSC heating technique followed by analysis using the Kissinger–Akahira–Sunose (KAS) method where values of apparent activation energy (E a) were estimated as a function of extent of conversion (α). The variations in E a with α on kinetic analysis from α = 0.10 to 0.88 for the amorphous to form I conversion suggested more complex processes, possibly liquid–solid and solid–solid transformations prior to formation of the form I.