Zhou Yang, Dong Wujun, Ye Jun, Hao Huazhen, Zhou Junzhuo, Wang Renyun, Liu Yuling
a State Key Laboratory of Bioactive Substance and Function of Natural Medicines and.
b Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing , PR China.
Drug Deliv. 2017 Nov;24(1):720-728. doi: 10.1080/10717544.2017.1311968.
Phospholipid complex is one of the most successful approaches for enhancing oral bioavailability of poorly absorbed plant constituents. But the sticky property of phospholipids results in an unsatisfactory dissolution of drugs. In this study, a matrix dispersion of baicalein based on phospholipid complex (BaPC-MD) was first prepared by a discontinuous solvent evaporation method, in which polyvinylpyrrolidone-K30 (PVP-K30) was employed for improving the dispersibility of baicalein phospholipid complex (BaPC) and increasing dissolution of baicalein. The combination ratio of baicalein and phospholipids in BaPC-MD was 99.39% and baicalein was still in a complete complex state with phospholipid in BaPC-MD. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM) and Fourier Transform Infrared (FTIR) analyzes demonstrated that baicalein was fully transformed to an amorphous state in BaPC-MD and phospholipid complex formed. The water-solubility and n-octanol solubility of baicalein in BaPC-MD significantly increased compared with those of pure baicalein. Compared with baicalein and BaPC, the cumulative dissolution of BaPC-MD at 120 min increased 2.77- and 1.23-fold, respectively. In vitro permeability study in Caco-2 cells indicated that the permeability of BaPC-MD was remarkably higher than those of baicalein and BaPC. Pharmacokinetic study showed that the average C of BaPC-MD was significantly increased compared to baicalein and BaPC. AUC of BaPC-MD was 5.01- and 1.91-fold of baicalein and BaPC, respectively. The novel BaPC-MD significantly enhanced the oral bioavailability of baicalein by improving the dissolution and permeability of baicalein without destroying the complexation state of baicalein and phospholipids. The current drug delivery system provided an optimal strategy to significantly enhance oral bioavailability for poorly water-soluble drugs.
磷脂复合物是提高难吸收植物成分口服生物利用度最成功的方法之一。但磷脂的粘性导致药物溶解不理想。本研究首次采用非连续溶剂蒸发法制备了基于磷脂复合物的黄芩苷基质分散体（BaPC-MD），其中聚乙烯吡咯烷酮-K30（PVP-K30）用于改善黄芩苷磷脂复合物（BaPC）的分散性并增加黄芩苷的溶解度。BaPC-MD中黄芩苷与磷脂的结合比例为99.39%，且黄芩苷在BaPC-MD中仍与磷脂处于完全复合状态。差示扫描量热法（DSC）、X射线衍射（XRD）、扫描电子显微镜（SEM）和傅里叶变换红外光谱（FTIR）分析表明，黄芩苷在BaPC-MD中完全转变为无定形状态并形成了磷脂复合物。与纯黄芩苷相比，黄芩苷在BaPC-MD中的水溶性和正辛醇溶解度显著增加。与黄芩苷和BaPC相比，BaPC-MD在120分钟时的累积溶出度分别提高了2.77倍和1.23倍。在Caco-2细胞中的体外渗透性研究表明，BaPC-MD的渗透性明显高于黄芩苷和BaPC。药代动力学研究表明，与黄芩苷和BaPC相比，BaPC-MD的平均血药浓度显著增加。BaPC-MD的AUC分别是黄芩苷和BaPC的5.01倍和1.91倍。新型BaPC-MD通过改善黄芩苷的溶解和渗透性，同时不破坏黄芩苷与磷脂的络合状态，显著提高了黄芩苷的口服生物利用度。当前的药物递送系统为显著提高难溶性药物的口服生物利用度提供了一种优化策略。
