Module 3 2019

Ignore Polymorphism at Your Peril - 1!

➢ An example from the literature – Ritonavir (Norvir, Abbott, HIV protease inhibitor) ➢ Initially sold as hard capsule with semi-solid solution of drug, approved in August 1996 ➢ >240 lots made before May – June 1998 ➢ Then DISASTER a second (Form II, thermodynamically more stable) polymorph suddenly appeared: o Form II 50 % lower intrinsic solubility than Form I o Failed dissolution release testing o Reduced bioavailability o Product withdrawn from market (>$ 250 M lost sales)

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