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首页> 外文期刊>Journal of pharmaceutical sciences. >Development of a supersaturable SEDDS (S-SEDDS) formulation of paclitaxel with improved oral bioavailability.
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Development of a supersaturable SEDDS (S-SEDDS) formulation of paclitaxel with improved oral bioavailability.

机译：紫杉醇过饱和SEDDS（S-SEDDS）制剂的开发具有改善的口服生物利用度。

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A new, supersaturable self-emulsifying drug delivery system (S-SEDDS) of paclitaxel was developed employing hydroxypropyl methylcellulose (HPMC) as a precipitation inhibitor with a conventional SEDDS formulation. In vitro dilution of the S-SEDDS formulation results in formation of a microemulsion, followed by slow crystallization of paclitaxel on standing. This result indicates that the system is supersaturated with respect to crystalline paclitaxel, and the supersaturated state is prolonged by HPMC in the formulation. In the absence of HPMC the SEDDS formulation undergoes rapid precipitation, yielding a low paclitaxel solution concentration. A pharmacokinetic study was conducted in male Sprague-Dawley rats to assess exposure after an oral paclitaxel dose of 10 mg/kg in the SEDDS formulations with (S-SEDDS) and without HPMC. The paclitaxel S-SEDDS formulation shows approximately 10-fold higher maximum concentration (C(max)) and five-fold higher oral bioavailability (F approximately 9.5%) compared with that of the orally dosed Taxol((R)) formulation (F approximately 2.0%) and the SEDDS formulation without HPMC (F approximately 1%). Coadministration of cyclosporin A (CsA), an inhibitor of P-glycoprotein and CYP 3A4 enzyme, at a dose of 5 mg/kg with the S-SEDDS formulation further increased the oral bioavailability (F approximately 22.6%). This assessment demonstrates that the systemic exposure of paclitaxel following oral administration can be substantially improved via the S-SEDDS approach.
机译：开发了一种新的紫杉醇超饱和自乳化药物输送系统（S-SEDDS），它采用羟丙基甲基纤维素（HPMC）作为沉淀抑制剂，采用常规SEDDS配方。 S-SEDDS制剂的体外稀释导致微乳液的形成，随后紫杉醇在静置时缓慢结晶。该结果表明该系统相对于结晶紫杉醇而言是过饱和的，并且配方中的HPMC可以延长过饱和状态。在没有HPMC的情况下，SEDDS制剂会快速沉淀，从而导致紫杉醇溶液浓度低。在雄性Sprague-Dawley大鼠中进行了药代动力学研究，以评估口服紫杉醇剂量为10 mg / kg的含（S-SEDDS）和不含HPMC的SEDDS制剂的暴露情况。与口服紫杉醇制剂相比，紫杉醇S-SEDDS制剂的最大浓度（C（max））高约10倍，口服生物利用度（F约9.5％）约高5倍。 2.0％）和不含HPMC的SEDDS配方（F约为1％）。 P-糖蛋白和CYP 3A4酶抑制剂环孢菌素A（CsA）以5 mg / kg的剂量与S-SEDDS制剂共同给药进一步提高了口服生物利用度（F约为22.6％）。该评估表明，口服给药后紫杉醇的全身暴露可通过S-SEDDS方法得到显着改善。

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