替硝唑胃漂浮小丸的制备及体外释药

Studies on the preparation of intragastric floating pellets containing Tinidazole and the characteristics of drug release in vitro

目的:研制替硝唑胃漂浮小丸,并对其体外释药特性进行研究。方法:以海藻酸钠为载体材料,采用离子胶凝法制备替硝唑胃漂浮小丸;以包封率、漂浮性能和体外释药特性为指标,通过单因素试验考察替硝唑与海藻酸钠比例、十六醇与海藻酸钠比例、海藻酸钠溶液浓度及制备工艺对小丸的影响,筛选优化处方和工艺;通过体外释药试验,考察溶出介质pH、离子强度及搅拌转速对小丸体外释药的影响。结果:小丸的优化处方及制备工艺为质量分数1%的海藻酸钠,海藻酸钠∶十六醇∶替硝唑质量比为1∶4∶3,替硝唑与十六醇加热熔融混匀后冷却固化,粉碎加至海藻酸钠溶液中制得混悬液,滴加至含氯化钙的凝胶液中形成小丸;小丸体外可缓慢释药达10 h以上,漂浮性能良好;随溶出介质pH值和搅拌转速增加,小丸释药有所加快;介质离子强度对小丸体外释药无显著影响。结论:替硝唑胃漂浮小丸具有胃内漂浮特性,可缓慢释放药物。

Objective： To prepare tinidazole intragastric floating pellets and investigate the characteristics of drug release in vitro.Methods： The intragastric floating pellets containing tinidazole were prepared by ionotropic gelation with sodium alginate as matrix material.The entrapment efficiency,floating and drug release characteristics were taken as criteria to optimize the formulation and preparation technology.The effects of pH values,ionic strength of dissolution media and rotation speeds on drug release were studied by in vitro dissolution test.Results： The optimal conditions of the intragastric floating pellets including the concentration of sodium alginate,the ratio of sodium alginate to cetyl alcohol and tinidazole were 1%（w/v）,1：4：3（w/w/w）,respectively.The powders of tinidazole and cetyl alcohol that were prepared by melting,and pulverizing were added to sodium alginate solution to prepare suspension,the intragastric floating pellets containing tinidazole were prepared by adding the suspension dropwise into CaCl2 gelling solution.The pellets remained floating and release drug for more than 10 h in vitro.The rate of drug release increased with increasing the pH of media and rotation speeds.The ionic strength of dissolution media had little influence on drug release rate in vitro.Conclusion： Tinidazole intragastric floating pellets exhibit excellent release characteristics in vitro and float well in simulated gastric fluid.