玉米醇溶蛋白黏附控释片的制备及体外评价和体内药动学研究

Preparation,in Vitro Evaluation and in Vivo Pharmacokinetics of Bioadhesive Controlled-release Tablets with Zein as Main Excipient

目的:制备玉米醇溶蛋白黏附控释片,考察其体外黏附性能和释药行为以及体内药动学特性。方法:以玉米醇溶蛋白为骨架和黏附材料,5-氟尿嘧啶为模型药物,制备胃肠道生物黏附控释片,并将其与市售普通片剂和自制控释片进行体外黏附性能和释药行为以及大鼠体内药动学比较。结果:用玉米醇溶蛋白包衣的5-氟尿嘧啶黏附控释片具有良好的组织黏附性,体外释放在12小时之内符合零级释放,达到了控释目的,且与参比制剂相比,其在大鼠胃肠道的滞留时间更长,药物释放更平稳,缓释效应明显。结论:玉米醇溶蛋白对胃肠道黏膜具有良好的生物黏附性,将其用作包衣材料制备黏附控释片,可实现药物在胃肠道的缓控释。

Objective： To prepare the bioadhesive controlled-release tablets with zein as main excipient and to evaluate their in vitro adhesive ability and release profile as well as in vivo pharmacokinetics. Methods： The gastrointestinal adhesive controlled-release tablets were prepared using zein as matrix and adhesive material and 5-fluorouracil（5-FU） as model drug. Their in vitro adhesive ability and release profile as well as pharmacokinetics in rats were compared with common market tablets and homemade controlled-release tablets. Results： The 5-FU gastrointestinal adhesive controlled-release tablets had good tissue adhesion. Their in vitro release met zero-order model within 12 h, reaching the con- trolled-release. Compared with control tablets, their retention in the ratgastrointestinal tract was longer and their release was more stable and sustained. Conclusion： Zein has showed a good bioadhesion in gastroin- testinal tract. The bioadhesive controlled-release tablets using zein as main excipient could achieve sustained- and controlled-release in gastrointestinal tract.