A parenteral docetaxel-loaded lipid microsphere with decreased 7-epidocetaxel conversion in vitro and in vivo

The purpose of the study was to develop a parenteral docetaxel lipid microsphere to inhibit its 7-epidocetaxel conversion in vitro and in vivo. 7-epidocetaxel conversion as the main indicator was investigated to optimize the formulation and process. 10% medium-chain triglyceride/long-chain triglyceride (3:1) as the oil phase, egg lecithin E80 as the emulsifier and 0.02% NaHSO₃ as the acidity regulator were selected to prepare docetaxel lipid microsphere. This study found that pH and temperature were dominant factors on the epimerization of docetaxel in lipid microsphere, and that optimum conditions were a pH of 5.3 and thermal sterilization conditions of 121°Cautoclaving for 8min. According to the degradation kinetics, docetaxel lipid microsphere had a wider pH range where 7-epidocetaxel(%) stayed at low levels than Docetaxel for Injection, and might improve the docetaxel stability by loading drug in lecithin layer instead of altering the degradation mechanism. Docetaxel lipid microsphere decreased epimerization in plasma in vitro obviously. Pharmacokinetics of docetaxel and 7-epidocetaxel were investigated to quantify the 7-epidocetaxel conversion in vivo. The resulrs indicated that there was less conversion of docetaxel in lipid microspheres than in Docetaxel for Injection. The convert ratios were 0.61% and 3.04% respectively. In conclusion, lipid microsphere is a promising delivery system for intravenous administration of docetaxel with decreased 7-epidocetaxel conversion.