EFFECT OF CYCLODEXTRIN COMPLEXATION ON THE CHEMICAL-STABILITY OF DOXORUBICIN AND DAUNORUBICIN IN AQUEOUS-SOLUTIONS

The influences of cyclodextrins on the chemical stability of the antineoplastic drugs doxorubicin and daunorubicin in aqueous media have been studied using a stability-indicating high-performance liquid chromatographic method. Various parameters, such as cyclodextrin structure, pH, structure of the anthracycline, cyclodextrin concentration and the presence of a co-solvent, were investigated. In the acidic region, the degradation rates of both doxorubicin and daunorubicin decrease in the presence of gamma-cyclodextrin, whereas alpha- and beta-cyclodextrin show no effect in acid as well as in alkaline media. Above pH 4 the degradation of daunorubicin is accelerated by gamma-cyclodextrin, while for doxorubicin this effect is only observed in strong alkaline solutions. On complexation, the order of the reactions as well as the degradation mechanisms of the anthracyclines do not change. In the presence of acetonitrile the anthracycline-gamma-cyclodextrin complexes decompose because the organic co-solvent is embedded in the cavity of the cyclodextrin host.