Wu Weiwei, Zu Yuangang, Zhao Xiuhua, Zhang Xinxin, Wang Lingling, Li Yuanyuan, Wang Li, Zhang Yin, Lian Bolin
a Key Laboratory of Saline-alkali Vegetation Ecology Restoration in Oil Field (SAVER), Ministry of Education , Alkali Soil Natural Environmental Science Center (ASNESC), Northeast Forestry University , Harbin , China.
b Key Laboratory of Forest Plant Ecology , Northeast Forestry University, Ministry of Education , Harbin , China.
Drug Dev Ind Pharm. 2017 Aug;43(8):1366-1377. doi: 10.1080/03639045.2017.1318900. Epub 2017 Apr 24.
Apigenin (AP) has many pharmacological activities. AP has poor solubility in some solvents. AP is insoluble in water and slightly soluble in ethanol (1.93 mg/ml). It has limited application and exploitation. Therefore, the liquid antisolvent precipitation (LAP) method was applied to improve the solubility of AP in ethanol by changing its crystal form or producing ultra-fine particles. Then, the inclusion complex of AP with 2-Hydroxypropyl-β-cyclodextrin (HP-β-CD) is prepared using the solvent removal method. The effects of various experimental parameters on the solubility of AP in ethanol were investigated through the single factor design. Under the optimum conditions, the AP-ethanol solution of 6.19 mg/ml was obtained. The inclusion complex of AP with HP-β-CD was obtained by the solvent removal method. The load efficiency (LE) and drug encapsulation efficiency (EE) of the inclusion complex of AP with HP-β-CD were 13.98%±0.14% and 97.86%±1.07%, respectively. SEM, FTIR, HNMR, XRD, DSC and TG were used to analyze the characteristics of the inclusion complex of AP with HP-β-CD. These results showed that the inclusion complex has significantly different characteristics with AP. In addition, the dissolution rate and solubility of the inclusion complex were approximately 15.24 and 68.7 times higher than AP in artificial gastric juice, and was separately 10.4 times and 40.05 times higher than AP in artificial intestinal juice. The bioavailability of inclusion complex increased 3.97 times compared with AP.
芹菜素（AP）具有多种药理活性。AP在某些溶剂中的溶解度较差。它不溶于水，微溶于乙醇（1.93毫克/毫升）。其应用和开发受到限制。因此，采用液体抗溶剂沉淀（LAP）法通过改变AP的晶型或制备超细颗粒来提高其在乙醇中的溶解度。然后，采用溶剂去除法制备了AP与2-羟丙基-β-环糊精（HP-β-CD）的包合物。通过单因素设计研究了各种实验参数对AP在乙醇中溶解度的影响。在最佳条件下，获得了浓度为6.19毫克/毫升的AP-乙醇溶液。通过溶剂去除法得到了AP与HP-β-CD的包合物。AP与HP-β-CD包合物的负载效率（LE）和药物包封率（EE）分别为13.98%±0.14%和97.86%±1.07%。采用扫描电子显微镜（SEM）、傅里叶变换红外光谱（FTIR）、核磁共振氢谱（HNMR）、X射线衍射（XRD）、差示扫描量热法（DSC）和热重分析法（TG）对AP与HP-β-CD包合物的特性进行了分析。这些结果表明该包合物与AP具有显著不同的特性。此外，该包合物在人工胃液中的溶出速率和溶解度分别约为AP的15.24倍和68.7倍，在人工肠液中分别是AP的10.4倍和40.05倍。包合物的生物利用度比AP提高了3.97倍。
