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目的:以卡波姆和壳聚糖为生物黏附材料,制备斑蝥素多单元胃黏附缓释片,以提高斑蝥素的口服生物利用度,并得到平稳持久的释药效果。方法:制备斑蝥素β-环糊精包合物,通过单因素试验筛选黏附材料,正交试验优选斑蝥素胃黏附缓释片的处方,考察该制剂在大鼠体内的黏附性、体外释放度及其在比格犬体内的口服生物利用度。结果:以卡波姆934-壳聚糖(1∶1)为黏附材料,每片黏附片的处方为斑蝥素5 mg,β-环糊精175 mg,卡波姆934 50 mg,壳聚糖50 mg,交联聚维酮80 mg,硬脂酸镁4 mg。斑蝥素胃黏附缓释片在体外3 h时释放度25%~35%,12 h时释放度≥85%。8 h后制剂依然黏附在Wistar大鼠的胃黏膜表面。Beagle犬口服片剂后,药物在体内可缓慢、持久释放,相对生物利用度172%。结论:体内、外研究表明制备的斑蝥素黏附片具有良好的胃黏附性能和缓释特性,且血药浓度平稳持久,生物利用度显著提高。
OBJECTIVE: To prepare carborandin multi-unit gastric adhesion sustained-release tablets by taking carbomer and chitosan as bioadhesive materials to improve the oral bioavailability of cantharidin and to obtain a steady and sustained release effect. Methods: The inclusion compound of cantharidin β-cyclodextrin was prepared. The adhesive material was screened by single factor test. The prescription of cantharidin gastric mucosal sustained-release tablets was optimized by orthogonal test. The adhesiveness, in vitro release And its oral bioavailability in beagle dogs. RESULTS: With carbomer 934-chitosan (1: 1) as the adherent material, the prescriptions of each tablet were cantharidin 5 mg, β-cyclodextrin 175 mg, carbomer 934 50 mg, chitosan 50 mg, crospovidone 80 mg, magnesium stearate 4 mg. Cantharidin gastric adhesion sustained-release tablets in vitro release of 3 h at 25% to 35%, 12 h release of ≥ 85%. After 8 h the formulation still adhered to the gastric mucosal surface of Wistar rats. Beagle dogs oral tablets, the drug in the body can be slow, sustained release, the relative bioavailability of 172%. Conclusion: In vivo and in vitro studies show that the prepared cantharidin adhesive sheet has good gastric adhesion properties and sustained release characteristics, and the plasma concentration is stable and long lasting, and the bioavailability is significantly increased.