Effect of additives on stability of etoposide in PLGA microspheres.

The purpose of this article was to determine the shelf life of etoposide in poly(lactic-co-glycolic acid) (PLGA) microspheres prepared with and without additives (i.e., tricaprin and isopropyl myristic acid ester [IPM]). The microspheres were prepared by a single-emulsion solvent extraction technique with and without 25% w/w additive. The batches of microspheres were subjected to an accelerated stability study at two elevated temperatures (70 degrees C and 80 degrees C or 80 degrees C and 90 degrees C). Samples were taken at 7, 14, 21, 28, and 35 days for estimation of drug content by high-performance liquid chromatography (HPLC). The drug stability in the microspheres was determined by plotting the log percentage drug remaining versus time to obtain the degradation rate constant k of etoposide at the measured temperature. This degradation rate constant was then used in the Arrhenius equation to obtain the activation energy of etoposide, which was utilized to determine the shelf life of the microspheres at room temperature. The results showed that all three microsphere formulations had good long-term stability at room temperature (6.62-8.86 years at 25 degrees C). The plain microspheres were shown to possess a shelf life of 6.62 years, and the IPM and tricaprin were the most stable with shelf lives of 8.25 and 8.86 years, respectively.