Abstract
The kinetics of oxidation of the HMG-CoA reductase inhibitors lovastatin, simvastatin, L-157,012, and L-647,318 were studied in an aqueous surfactant solution. A thermally labile free radical initiator was used to attain measurable reaction rates at 40°C and rate constants were determined by measuring oxygen consumption using an oxygen electrode. The stability of the drugs was found to increase in the order lovastatin = simvastatin < L-157,012 < L-647,318. The addition of butylated hydroxyanisole (BHA) was found to stabilize the drugs. For the oxidation of lovastatin, the effectiveness of antioxidants increased in the order propyl gallate < BHA < alpha-tocopherol. It is concluded that the stability of oxidizable drugs can be rapidly and conveniently assessed by the techniques described herein.
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Kaufman, M.J. Applications of Oxygen Polarography to Drug Stability Testing and Formulation Development: Solution-Phase Oxidation of Hydroxymethylglutaryl Coenzyme A (HMG-CoA) Reductase Inhibitors. Pharm Res 7, 289–292 (1990). https://doi.org/10.1023/A:1015886415210
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DOI: https://doi.org/10.1023/A:1015886415210