热熔挤出法制备的非诺贝特纳米骨架系统的体外释放和口服生物利用度研究（英文）

In vitro dissolution and oral bioavailability study of fenofibrate nanomatrix system prepared by hot-melt extrusion

溶剂挥发法制备纳米骨架具有有机溶剂残留、环境污染、需要防爆保护等缺点。本文使用多孔二氧化硅Sylysia~?350(S350)和pH敏感材料Eudragit~?L100-55(EL100-55)采用热熔挤出法(HME)制备了一系列的非诺贝特纳米骨架给药系统,并比较了它们的体外溶出及体内生物利用度,最后选择体内生物利用度最高的处方,进行DSC和PXRD的表征。结果表明,尽管纳米骨架系统中仍然存在结晶态的药物,但其相对于市售制剂依然有着更好的溶出速率和更高的大鼠口服生物利用度。与市售制剂相比,最优化处方的口服生物利用度是市售制剂的157.1%;与溶剂挥发法相比,最优化处方的口服生物利用度是溶剂挥发法的124.8%,热熔挤出法制备的纳米骨架在提高生物利用度方面更具优势。总之,热熔挤出法也可以作为制备纳米骨架给药系统的一种选择。

Solvent evaporation method for preparation of nanomatrix has the disadvantages,such as residual organic solvent,environmental pollution,explosion-proofing and so on.To overcome these shortcomings,a series of fenofibrate nanomatrix drug delivery system(NDDS)consisting of nano-porous silica Sylysia■350(S350)and pH sensitive material Eudragit■L100-55(EL100-55)were prepared using hot-melt extrusion(HME),and their in vitro dissolution and in vivo bioavailability were compared.Finally,the formulation with the highest in vivo bioavailability was selected as the optimized formulation for DSC and PXRD characterization.The results showed that the optimized NDDS showed a higher bioavailability than the reference formulation,although there was crystalline form drug remaining in NDDS.The relative bioavailability of the optimized formulation was 157.1%compared with the commercial product Lipanthyl■.In addition,the relative bioavailability of the optimized formulation was 124.8%in comparison with the formulation prepared by solvent evaporation method,showing that the NDDS prepared by the HME method was effective in improving the bioavailability of fenofibrate.In conclusion,HME was a promising method to prepare NDDS.