格列齐特生物黏附缓释片的研制及其体内体外评价

Preparation and in Vitro and in Vivo Evaluation of Gliclazide Bioadhesive Sustained Release Tablets

目的考察格列齐特生物黏附性缓释片体外释药行为,离体组织黏附力,以及在犬体内的药动学。方法以羟丙基甲基纤维素(HPMC)和卡波姆(Carbopol,CP)为生物黏附材料和骨架材料,乳糖为稀释剂制备生物黏附性缓释片。以磷酸盐缓冲液(pH8.6)为溶出介质,测定生物黏附性缓释片的释放度。以自制黏附力测定装置测定片剂对家兔离体胃、肠组织的黏附力。采用HPLC测定犬血浆中的格列齐特浓度,研究格列齐特生物黏附性缓释片与格列齐特Ⅱ片在beagle犬体内的药动学和相对生物利用度。结果生物黏附性缓释片体外释放符合缓释制剂要求,其与家兔离体胃、肠组织的黏附力明显大于普通片剂,且与肠的黏附力大于与胃的黏附力。格列齐特生物黏附缓释片对格列齐特Ⅱ片的相对生物利用度为(282.74±20.75)%。结论格列齐特生物黏附缓释片在胃、肠道具有较强的黏附作用,利用生物黏附技术可以提高格列齐特的生物利用度。

OBJECTIVE To prepare Gliclazide bioadhesive sustained release tablets and investigate the in vitro release characteristics,adhesion in the ex vivo tissues and the pharmacokinetics in beagle dogs. METHODS Bioadhesive sustained release tablets were prepared with HPMC and Carbopol as bioadhesive and framework materials and lactose as diluent bases. The in vitro release characteristics of Gliclazide bioadhesive sustained release tablets were evaluated in phosphate buffer （pH 8.6） medium by determining the dissolution rate. A self-made adhesion detector was used to compare the adhesive force to rabbit stomach or small intestine. Gliclazide concentration in beagle dogs plasma at different sampling time was determined by HPLC for the pharmacokinetics and relative bioavailability study. The results were compared with that of the Gliclazide （Ⅱ） tablets. RESULTS The in vitro release of Gliclazide bioadhesive sustained release tablets was consistent with the requirement of sustained release prepararions. The adhesion of bioadhesive sustained release tablets to ex vivo gastrointestinal mucosa of rabbits was stronger than of the common tablets, and the bioadhesion to small intestines mucosa was stronger than to gastric mucosa. The relative bioavailability of Gliclazide bioadhesive sustained release tablets to Gliclazide（Ⅱ） tablets was （282.74±20. 75 ） %. CONCLUSION The adhesive force to intestine mucosa of Gliclazide bioadhesive sustained release rablets is stronger than that to gastric mucosa. The bioavailability is elevated by bioadhesive technology.