Ritonavir Form III: A Coincidental Concurrent Discovery

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 was observed in 2014, it was not characterized as a unique polymorph until 2022 when, coincidentally, a team at AbbVie and the authors of this manuscript independently discovered Form III via melt/cool crystallization. This study builds upon the discovery through a thorough characterization and novel thermal profile for quicker nucleation and crystallization of the new form.