Investigation of drug polymorphism: Case of artemisinin

•The Artemisinin dimorphic system was found to be enantiotropic.•The Orthorhombic modification is the form stable at low-temperatures and the triclinic modification the form stable at high-temperatures.•The polymorphic phase transition occurs at ∼130 °C.

The polymorphism of the anti-malarial compound artemisinin was examined. The phase behavior of solid artemisinin has experimentally been investigated using differential scanning calorimetry and temperature-resolved X-Ray powder diffraction. In addition, complementary solution studies and suspension experiments were performed. The results clearly confirm the existence of two modifications of artemisinin, which are related enantiotropically. The orthorhombic modification is the thermodynamically stable form at low temperatures, while the triclinic form is the stable one at higher temperatures with a transition temperature of ∼130 °C. Problems associated with analysis of the polymorphic phase behavior are comprehensively addressed.