He Suna, Duan Lengxin, Li Yan, Cui Zheng, Zhang Xiaofei
Department of Pharmaceutical Sciences, Medical College, Henan University of Science and Technology, Luoyang, PR China.
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, PR China.
Pak J Pharm Sci. 2020 Nov;33(6):2489-2495.
Because of the low solubility, the oral bioavailability of simvastatin (SV) was poor, which restricted the application in clinic. In order to increase the dissolution and the oral absorption of simvastatin, we prepared a novel solid nanomatrix of SV with pharmaceutical acceptable nano-sized silica and Eudragit®. The nanomatrix was prepared using solvent evaporate method and the formulation was optimized. The X-ray diffraction (XRD) and differential scanning calorimetry (DSC) were used to analyze the physicochemical characterization of the SV nanomatrix. The results indicated that the SV existed in the nanomatrix was in a state of molecule or amorphous form. The optimal formulation, consisted of SV, Eudragit® L100-55 and Sylysia 350 (1:5:5, w/w/w), significantly enhanced the dissolution of SV compared with Zocor. And the relative bioavailability was 272% to Zocor. The oral absorption of simvastatin was enhanced markedly. The SV nanomatrix after storage for 1 year displayed similar performance in vitro and in vivo with the freshly prepared nanomatrix. The stability of SV nanomatrix achieved the desired objectives. In conclusion, the nanomatrix system described here had superior performance in vitro and in vivo and was expected to have a promising future as an alternative oral drug delivery system for SV.
由于辛伐他汀（SV）的低溶解度，其口服生物利用度较差，这限制了它在临床上的应用。为了提高辛伐他汀的溶出度和口服吸收，我们用可药用的纳米二氧化硅和丙烯酸树脂制备了一种新型的辛伐他汀固体纳米基质。采用溶剂蒸发法制备纳米基质并对其配方进行了优化。利用X射线衍射（XRD）和差示扫描量热法（DSC）分析了辛伐他汀纳米基质的物理化学特性。结果表明，存在于纳米基质中的辛伐他汀呈分子态或无定形状态。由辛伐他汀、丙烯酸树脂L100 - 55和Sylysia 350（1:5:5，w/w/w）组成的最佳配方与舒降之相比显著提高了辛伐他汀的溶出度。其相对生物利用度是舒降之的272%。辛伐他汀的口服吸收显著增强。储存1年后的辛伐他汀纳米基质在体外和体内表现与新制备的纳米基质相似。辛伐他汀纳米基质的稳定性达到了预期目标。总之，本文所述的纳米基质系统在体外和体内均具有优异性能，有望作为辛伐他汀的替代口服给药系统拥有广阔前景。
