A novel oxidative stressing system is described which generates high levels of peroxy radicals in solution at room temperature, without the use of azonitrile initiators. The oxidative stressing system is composed of a 10% solution of Tween 80 in water to which FeCl3 x 6H2O is added. The Tween 80 acts as a solubilizing agent for drug compounds, and also contains substantial amounts of organic hydroperoxides. It is shown that the Fe III/ Fe II couple operates on the hydroperoxide concentration to effectively generate new peroxy radicals, which then propagate in the Tween 80 solution. Key features of the Tween 80/Fe III system are investigated, and the oxidizability of seven known compounds and ten developmental compounds are examined. Relative reaction rates span a 300-fold range, from benzoic acid (nonreactive, defined as <0.5% reacted per day) to Vitamin D3 (7% reacted per hour). Oxidizability "rankings" thus generated are shown to agree well with azonitrile initiated oxidative stress. The potential for general correlations between this type of oxidizability data and actual oxidative performance in LFC and solid oral dosage forms is discussed.
(c) 2006 Wiley-Liss, Inc. and the American Pharmacists Association.