Abstract:

Aim To prepare a self-emulsifying microemulsion of 9-nitrocamptothecin (9-NC ME) for intravenous injection and investigation of its pharmacokinetic profiles in normal SD rats. Methods 9-NC ME was optimized in terms of droplet size and lack of drug precipitation following aqueous dilution using a pseudo-ternary phase diagram. Physicochemical properties of 9-NC ME were evaluated. 9-NC ME was intravenously administered via tail vein in healthy rats. Results A stable microemulsion was formulated consisted of soybean oil as oil phase, EPC/Tween-80 as emulsifier, and anhydrous ethanol as co-emulsifier. The droplets of the microemulsion were spherical shape with mean diameter of 38.3 ± 4.0 nm after 1:20 dilution with 5% glucose injection. The pharmacokinetic parameters of 9-NC ME after intravenous administration in rats were t1/2 of 0.97 ± 0.14 h, AUC0-∞ of 372.77 ± 49.62 ng·h·mL^-1, and MRT of 1.40 ± 0.21 h which were 1.4-fold, 1.65-fold, and 1.4-fold more than those of 9-NC solution (P<0.01). Conclusion The results suggested that 9-NC ME was a promising drug delivery system and it was expected to provide a novel 9-NC injection for cancer patients.

Key words: 9-Nitrocamptothecin, 9-Nitrocamptothecin, Self-emulsifying microemulsion, Self-emulsifying microemulsion, Injection, Injection, Pharmacokinetics, Pharmacokinetics