Etoposide was incorporated in lipid emulsion to develop an i.v. formulation, and improve its physical and chemical stability without addition of organic solvents, for use as a commercial formulation. High-pressure homogenization was used to prepare the lipid nanospheres and localize the drug at the surfactant layer. The particle size distribution and zeta potential were measured using photon correlation spectroscopy (PCS). Ultrafiltration was used to estimate the relative percentage of etoposide in each phase. The stability profile of etoposide in the lipid emulsion at various temperatures, pH values, and concentrations of drug was monitored by high performance liquid chromatography (HPLC). The degradation pattern of etoposide in lipid emulsion followed pseudo-first-order kinetics. The shelf life (T(90%)) of etoposide in lipid emulsion was estimated to be 47 days at 25 degrees C and it would be stable when stored for 427 days at 4 degrees C, which is a significant improvement compared with a stability of 9.5 days in aqueous solution at 25 degrees C. Etoposide in lipid emulsion and aqueous solution were both most stable at pH 5.0 with a half-life of 54.7 h and 38.6 min at 80 degrees C, respectively. The hydrolysis kinetics of etoposide in lipid emulsion was also shown to be dependent on the drug concentration.
Copyright 2007 Wiley-Liss, Inc.