Novel Eudragit® -based polymeric nanoparticles for sustained release of simvastatin

This paper reports on the development of nanoparticles aiming at the in vitro controlled release of simvastatin (SVT). The nanoparticles were prepared by the nanoprecipitation method with polymers Eudragit® FS30D (EDGFS) or Eudragit® NE30D (EDGNE). EDGFS+SVT nanoparticles showed mean size of 148.8 nm and entrapment efficiency of 76.4%, whereas EDGNE+SVT nanoparticles showed mean size of 105.0 nm and entrapment efficiency of 103.2%. Infrared absorption spectra demonstrated that SVT incorporated into the polymer matrix, especially EDGNE. Similarly, the differential scanning calorimeter (DSC) curve presented no endothermic peak of fusion, indicating that the system is amorphous and the drug is not in the crystalline state. The maintenance of SVT in the amorphous state may favors its solubilization in the target release sites. In the in vitro dissolution assay, the SVT incorporated into the EDGFS+SVT nanoparticles showed a rapid initial release, which may be related to the pH of the dissolution medium used. Regarding the EDGNE+SVT nanoparticles, the in vitro release occurred in a bimodal behavior, i.e., an initial “burst” followed by a sustained delivery, with the kinetics of drug release following Baker-Lonsdale’s mathematical model. All these features suggest the nanoparticulate system’s potential to modulate SVT delivery and enhance its bioavailability.

本研究报道了旨在实现辛伐他汀（simvastatin，SVT）体外控释的纳米颗粒的开发工作。该纳米颗粒采用纳米沉淀法制备，载体为Eudragit® FS30D（EDGFS）或Eudragit® NE30D（EDGNE）两种聚合物。其中，EDGFS+SVT纳米颗粒的平均粒径为148.8 nm，包封率达76.4%；EDGNE+SVT纳米颗粒的平均粒径为105.0 nm，包封率则为103.2%。红外吸收光谱证实，辛伐他汀已嵌入聚合物基质之中，尤其在EDGNE载体体系中负载效果更为突出。差示扫描量热法（differential scanning calorimeter，DSC）曲线未出现熔融吸热峰，表明该纳米颗粒体系呈无定形态，药物亦未处于结晶状态。辛伐他汀保持无定形态，或可促进其在目标释药位点的溶解。体外溶出试验结果显示，EDGFS+SVT纳米颗粒中的辛伐他汀呈现快速初始释放行为，这可能与实验所用溶出介质的pH值相关。而EDGNE+SVT纳米颗粒的体外释药则呈现双峰行为：即初始“突释”后伴随持续释药，其药物释放动力学符合Baker-Lonsdale数学模型。上述所有特性均表明，该纳米颗粒体系具备调控辛伐他汀递送、提升其生物利用度的应用潜力。