Module 3 Presentations

14/05/2024

The Wrong Formulation - Osmosin  Osmosin was an osmotically driven sustained release formulation of indomethacin designed to reduce GI effects of the drug  Withdrawn within 9 months of marketing: o Indomethacin highly gastric irritant o Osmotic core contained KCl (known to induce gastric ulcers in high localised concentrations) o Semi-permeable membrane became ‘sticky’ in GI fluid o Tablet adhered to GI wall and drilled holes in wall when hole was in direct contact o Excess reports of GI perforation and death (>7 patients in UK)

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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II 50 % lower intrinsic solubility than Form I o Failed dissolution release testing o Reduced bioavailability o Product withdrawn from market (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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