Identification of interpolymorph transformations of progesterone by terahertz time-domain spectroscopy

We utilized the terahertz time-domain spectroscopy system to differentiate the two polymorphs of progesterone and to identify the occurrence of interpolymorph transitions. The stable polymorph of progesterone was prepared by ethanol-mediated evaporating/cooling methods, and the metastable state was obtained by using pregnenolone as an additive. These two polymorphs show distinct different absorption spectrum in the terahertz region. As the metastable state of progesterone naturally converted to the stable state over time, the absorption mode of the metastable state disappeared and those of the stable state re-emerged. Interpolymorph transformations of progesterone can be rapidly identified using an apparent absorption mode as an indicator, which represents the existence of the metastable state of progesterone.