Predicting the ritonavir crisis by revisiting the polymorph landscape . . . Ritonavir is not bioavailable in the solid state, and thus the initial formulation of the drug product was a semi-solid capsule containing the drug dissolved in ethanol water based solutions 1, which was nearly saturated with form 1 6
Crystal size, shape, and conformational changes drive both the . . . - PNAS The most infamous of these cases is that of the HIV drug ritonavir (RVR): Once its reluctant form was unwillingly nucleated for the first time, its desired form could no longer be produced with the same manufacturing process
Could mechanochemistry have saved Abbott Laboratories $250 million? If conditions spontaneously favour the formation of a thermodynamically more stable form, all the crystals will convert to the new structure and it becomes almost impossible to access the original kinetic product
Ritonavirs Polymorph Discovery: Drug Development The drug substance was not dissolving properly, and a solid was precipitating out of the semisolid capsules The commercial lots were depleting rapidly, and the drug was severely diminishing its efficacy
Polymorphism: A Major Risk That Pharma Companies Must Mitigate In this blog, we highlight key elements of solid form screening, from origins to challenges, and report recent discoveries in the solid form landscape of the well-known antiviral drug Ritonavir
Ritonavir Near Disaster and Polymorphism | OpenOChem Learn The late 1990s witnessed a dramatic example of the impact of polymorphism with the HIV drug ritonavir Ritonavir, a protease inhibitor, was a major advance in HIV treatment However, it encountered a serious challenge In 1998, a new, more stable polymorph of ritonavir emerged during manufacturing
Late Appearing Polymorphs: Ritonavir - Improved Pharma In summary, there have been at least three different occurrences of late-appearing polymorphs for ritonavir: the original appearance of Form II, the appearance of the anhydrous form in 2005, and the appearance of Form III in 2022
Ritonavir Form III: A New Polymorph After 24 Years Polymorphism occurs widely in pharmaceutical solids, and must be thoroughly studied during product development Twenty-four years after ritonavir (RTV) Form II materialized, we report a new polymorph, Form III, discovered via melt crystallization