Fan Junting, Dai Yunhao, Shen Hongxue, Ju Jianming, Zhao Zhiying
School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese, Nanjing 210028, China.
Molecules. 2017 May 11;22(5):776. doi: 10.3390/molecules22050776.
In this study, a novel ternary complex system (TCS) composed of baicalein, phospholipids, and Soluplus was prepared to improve the flowability and dissolution for baicalein phospholipid complex (BPC). TCS was characterized using differential scanning calorimetry (DSC), infrared spectroscopy (IR), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The flowability, solubility, oil-water partition coefficient, in vitro dissolution, and in vivo pharmacokinetics of the system were also evaluated. DSC, IR, PXRD, and SEM data confirmed that the crystal form of baicalein disappeared in BPC and TCS. Furthermore, the angle of repose of TCS of 35° indicated an improvement in flowability, and solubility increased by approximately eight-fold in distilled water when TCS was compared with BPC (41.00 ± 4.89 μg/mL vs. 5.00 ± 0.16 μg/mL). Approximately 91.24% of TCS was released at the end of 60 min in 0.5% SDS (pH = 6.8), which suggested that TCS could improve the dissolution velocity and extent. Moreover, TCS exhibited a considerable enhancement in bioavailability with higher peak plasma concentration (25.55 μg/mL vs. 6.05 μg/mL) and increased AUC (62.47 μg·h/mL vs. 50.48 μg·h/mL) with 123.75% relative bioavailability compared with BPC. Thus, Soluplus achieved the purpose of improving the flowability and solubility of baicalein phospholipid complexes. The application of Soluplus to phospholipid complexes has great potential.
在本研究中，制备了一种由黄芩苷、磷脂和聚乙烯己内酰胺组成的新型三元复合体系（TCS），以改善黄芩苷磷脂复合物（BPC）的流动性和溶解性。采用差示扫描量热法（DSC）、红外光谱法（IR）、粉末X射线衍射法（PXRD）和扫描电子显微镜法（SEM）对TCS进行了表征。还评估了该体系的流动性、溶解度、油水分配系数、体外溶出度和体内药代动力学。DSC、IR、PXRD和SEM数据证实，黄芩苷的晶型在BPC和TCS中消失。此外，TCS的休止角为35°，表明其流动性有所改善，与BPC相比，TCS在蒸馏水中的溶解度增加了约8倍（41.00±4.89μg/mL对5.00±0.16μg/mL）。在0.5%十二烷基硫酸钠（pH = 6.8）中，约91.24%的TCS在60分钟结束时释放，这表明TCS可以提高溶出速度和程度。此外，与BPC相比，TCS的生物利用度显著提高，具有更高的血浆峰浓度（25.55μg/mL对6.05μg/mL）和增加的AUC（62.47μg·h/mL对50.48μg·h/mL），相对生物利用度为123.75%。因此，聚乙烯己内酰胺达到了改善黄芩苷磷脂复合物流动性和溶解度的目的。聚乙烯己内酰胺在磷脂复合物中的应用具有很大的潜力。
