An Automated Electroanalytical Method for the Drug Release Profiling of Liposomal Doxorubicin HCl Formulations

Abstract

Liposomes have emerged as a drug delivery system for various chemotherapeutics providing enhanced bioavailability and reduced toxicity. In vitro drug release profiling of liposomal formulations is one of the essential tests for the premarket approval and post market quality control. We developed an automated electroanalytical method for drug release profiling of liposomal doxorubicin formulation. In this electroanalytical method, square wave voltammetry mode was selected to determine the released drug, the only redox-active analyte, by measuring the current at the pulsed potential ranges. Therefore, no separation from liposomal encapsulated doxorubicin is needed. This electroanalytical method provided a continuous drug release measurement for 24 h. The drug release increased as the release media pH and temperature increased. At 37 °C, the drug release increased from 7 % to 40 % when the pH increased from 5.5 to 7.4, In addition, at pH 6.5, as the temperature increased from 37 °C to 52 °C, total drug release increased by more than two-fold. Complete drug release (more than 80 %) was obtained at pH 6.5 and 52 °C in less than 3 h. The brand name and the two generic formulations showed similar drug release profile in all experimental conditions. This method is an alternative to traditional methods which require separation steps such as dialysis or solid phase extraction to quantitate released doxorubicin. This method may be further applied in the in vitro release testing of other liposomal formulations containing redox-active drug substances, e.g., liposomes encapsulating daunorubicin.