Molnupiravir, a small molecule active pharmaceutical ingredient developed through a partnership between Merck and Ridgeback Biotherapeutics, was shown to be efficacious for the treatment of patients with COVID-19. Early in development it was discovered that molnupiravir can exist in two structurally similar polymorphic states. Detailed in this presentation will be the exhaustive studies to elucidate the structures of these polymorphs including single crystal X-ray diffraction, structure solution from high resolution powder diffraction, and crystal structure prediction was leveraged. Further discussion around the structural insights gained and how they relate to the physical properties of the two polymorphs will also be discussed. This knowledge informed and guided the control strategy to support the development of a large-scale manufacturing route suitable to meet the high material demands and to get this drug into the hands of patients around the world.
