In vitro equivalence assessment of rivaroxaban tablets

Background. Thrombotic conditions and complicationsa are among the leading causes of death and disability in high-income countries. The introduction of direct oral anticoagulants into clinical practice has expanded the possibilities of anticoagulant therapy. Having a broader spectrum of indications compared to other direct oral anticoagulants, rivaroxaban is also used to prevent atherothrombotic complications in patients with ischemic heart disease and peripheral artery disease. Rivaroxaban drugs are available as film-coated tablets in doses of 2.5 mg, 10 mg, 15 mg, and 20 mg. Currently, more than 45 generic versions of rivaroxaban are approved in Russia, which may differ in the source and particle size of the active pharmaceutical ingredient, as well as the excipient composition.

Aim. To assess the in vitro equivalence of brand-name vs. several generics of rivaroxaban that are available on the Russian market using the equivalence dissolution test.

Materials and methods. The study was performed on rivaroxaban film-coated tablets (2.5, 10, 15, and 20 mg): Xarelto® (Bayer AG, Germany) as the reference drug (D 0), and three randomly selected generic drugs (D 1, D 2, D 3). Dissolution kinetics were studied in hydrochloric acid solution, acetic, and phosphate buffer solutions, using an impeller mixer. The amount of dissolved drug was measured using high-performance liquid chromatography with ultraviolet detection. We used our own results along with data obtained from publicly available sources.

Results. The dissolution kinetics profiles of the generic drugs were similar to that of the reference drug. The dissolution speed of rivaroxaban from D 1 was not different from that of the reference drug D 0, which may be due to the use of a similar micronized form of the active ingredient. The results obtained for D 2 do not allow for a direct comparison because of the use of different dissolution media (including surfactants) in the experiments.

Conclusion. The use of a micronized active ingredient may give D 1 an advantage in the speed and completeness of dissolution, and predetermine high reproducibility of pharmacokinetic parameters in clinical use.