补骨脂素中空黏附微球胃滞留特性及体内外相关性研究

In vivo and In vitro Correlation and Retention of Psoralen Hollow Adhesive Microspheres

目的评价所制备的补骨脂素胃滞留中空黏附微球体内外胃滞留特性并探索其在大鼠体内外吸收相关性。方法通过乳化溶剂挥发法制备中空黏附微球,并对其胃内漂浮性、粘附性、滞留率和胃组织内药物浓度进行研究,通过测定不同时间药物体外溶出度和大鼠体内药物血药浓度得到中空黏附微球体外释放百分率和体内吸收百分数,采用Wagner-Nelson法对体内外吸收相关性进行分析。结果补骨脂素中空黏附微球胃内滞留率和胃内滞留药物浓度在2 h、4 h和6 h分别为78.7%±4.2%/13.95±4.92μg·mL^(-1),77%±10.41%/8.83±1.6μg·mL^(-1)和8.3%±18.9%/2.85±2.67μg·mL^(-1),胃腔平均通过时间(MPT)为5.66±0.55 h,体外释放平均驻留时间(MRT)为(4.36±0.35)h,体内吸收平均驻留时间(MRT)为(9.06±1.25)h;体内吸收百分数和体外释放百分率相关性分析得到两者相关系数R为0.9471,表明补骨脂素中空粘附微球体内外吸收相关性良好。结论中空黏附微球制剂体外漂浮性、粘附性,胃内滞留药物浓度结果显示其具有显著的胃滞留特性,而且体内外吸收相关性良好,体外释放数据能够预测大鼠体内的药动学行为。

Objective To evaluate the gastric retention characteristics of the prepared psoralen gastric retention hollow adhesive microspheres and to explore the correlation between the release in vitro and their absorption in vivo in rats.Methods The hollow adhesive microspheres were prepared by emulsification solvent volatilization method.The floating rate and the gastric retention rate of hollow adhesive microspheres was calculated by dissecting rats;The drug concentration in gastric tissue was obtained by homogenization method;The percentage of drug release in vitro and absorption of drug in vivo from hollow adhesive microspheres were obtained by measuring drug dissolution at different times and drug blood concentration in rats,respectively.The correlation between the drug release in vitro and the absorption in vivo were analyzed by Wagner-Nelson method.Results The gastric retention rate of psoralen hollow adhesive microspheres and gastric retention drug concentration at 2 h,4 h and 6 h were 78.7%±4.2%/13.95±4.92 μg·mL^(-1),77.0%±10.41%/8.83±1.6 μg·mL^(-1) and 8.3%±18.9%/2.85±2.67 μg·mL^(-1) respectively,the mean gastric transit time(MPT) is 5.66±0.55 h;The average residence time(MRT) of the hollow bioadhesive microspheres group in vitro release and in vivo absorption was 4.36±0.35 h and 9.06±1.25 h,respectively;The correlation analysis between the absorption percentage and the in release percentage shows that the correlation coefficient R is 0.9471,indicating that the correlation on absorption of the hollow adhesive microspheres in vivo and in vitro was good;Conclusion The results of the floating and adhesion of hollow adhesive microsphere preparations in vitro and the drug concentration retention in gastric showed that it has significant gastric retention characteristics,and the correlation of absorption between in vivo and in vitro is good.The data of drug release in vitro can predict the pharmacokinetic behavior in rats in vivo.