Ritonavir Form III: Lightning strikes twice at the same time, 137 miles apart

Polymorph screening is a crucial step in the characterization and development of pharmaceuticals. The 1998 recall of ritonavir upon the unexpected appearance of the more stable Form II polymorph remains a notorious case of disappearing polymorphs as the presence of Form II inhibited the ability to grow the original Form I. This study presents the characterization of Form III of ritonavir grown from melt/cool crystallization. While Form III has been observed by researchers in 2014 and 2022, this study presents a thorough characterization and novel thermal profile for quicker nucleation and crystallization of the new form. In this work, we expand upon past thermal methods examining the polymorphic landscape of ritonavir to shed light on the crystallization of Form III from the melt.