An Automated Capillary Electrophoresis Based Method for Drug Release Profiling of Liposomal Doxorubicin.

ABSTRACT

Liposomal doxorubicin hydrochloride is an antineoplastic agent widely used against human cancers. The data from in vitro drug release test (IVRT) is essential for quality and/or bioequivalence evaluation in drug approval and post-approval regulation of liposomal drug products. However, most of the currently available IVRT methods for liposomal doxorubicin hydrochloride have experimental deficiencies associated with liposomal rupture during the separation process which is needed for selective quantification of released drug from liposomal-bound drug. In addition, many of the methods are time consuming, requiring bulk quantities of liposomal drug product, and lack of automation. We have developed a selective, sensitive, and automated capillary electrophoresis (CE)-based IVRT method, measuring released doxorubicin without additional sampling and separation steps. This method requires a small volume of sample compared to currently available methods. The IVRT release study with liposomal doxorubicin was conducted at different temperatures and pH conditions. It was observed that the release profiles obtained for five formulations including the reference listed drug were similar at pH 6.50 and 47.0 °C. The drug release increased with the increase of media pH and temperature. Complete doxorubicin release (100 %) was obtained in 7 h at pH 6.50 and 47.0 °C, and in less than 3 h at pH 6.50 and 52.0 °C. This CE-based method can be extended for determination of the IVRT profiling of other liposomal drug products.