An Alternative Paclitaxel Self-Emulsifying Microemulsion Formulation: Preparation, Pharmacokinetic Profile, and Hypersensitivity Evaluation

Abstract

Based on the clinical fact that paclitaxel injection (Taxol®) frequently causes hypersensitivity reactions, an alternative paclitaxel self-emulsifying microemulsion was studied with phase diagrams, and the prescription of microemulsion formulation was optimized. Regarding Taxol, the pharmacokinetic parameters of microemulsion and hypersensitivity were investigated in rats and guinea pigs, respectively. The results showed that the self-emulsifying microemulsion was made up of tricaproin:tributyrin 1:1 as the oil phase, ethanol as assist, pluronic F68 and lecithin as emulsifier, and formed a mean diameter of 16 ± 3 nm when diluted with saline. In the pharmacokinetic study, rats were administrated Taxol or paclitaxel microemulsion. Blood samples were collected at definite time intervals, and plasma concentrations of paclitaxel were determined by high-performance liquid chromatography. The area under the curve was significantly higher in the microemulsion group (33 mg · ml⁻¹ · h) than that in the Taxol group (25 mg · ml⁻¹ · h) (P < 0.01). The constant of transport rate of speed, K₁₀ (0.55 h⁻¹), was much smaller in the microemulsion group compared with the Taxol group (1.55 h⁻¹). The mean retention time was 3.89 h in microemulsion group and 2.52 h in the Taxol group, showing the elimination rate was much slower in the former than in the latter. Compared with Taxol, the paclitaxel microemulsion caused less toxicity and had a longer circulation time in rats.