硝唑沙奈肠溶缓释颗粒体外释放度的测定  

Determination of the in vitro release rate of nitazoxanide enteric sustained-release particle

作　　者：陆泳良[1,2] 王霄旸[2] 郭沛[2] 费陈忠[2] 薛飞群[2] 方炳虎[1] 

机构地区：[1]华南农业大学兽医学院,广州510642 [2]中国农业科学院上海兽医研究所/中国农业科学院兽药安全评价与兽药残留研究重点开放实验室/农业部动物寄生虫学重点开放实验室,上海200241

出　　处：《南方农业学报》2013年第2期312-317,共6页Journal of Southern Agriculture

基　　金：上海市科委成果转化项目(9083919N1100)

摘　　要：【目的】建立硝唑沙奈肠溶缓释颗粒体外释放度的测定方法,为控制肠溶缓释颗粒剂的质量及提高硝唑沙奈(NTZ)治疗畜禽肠道疾病的效果提供参考依据。【方法】采用转篮法[转速75r/min,温度(37.0±0.5)℃,释放介质前2h为750mL2%十六烷基三甲基溴化铵(CTAB)0.1mol/mLHCl溶液,后加入250mL2%CTAB0.2mol/mL磷酸盐缓冲溶液,pH6.8,总体积1000mL]进行硝唑沙奈肠溶缓释颗粒的溶出试验,分别在不同时间点取样,以高效液相色谱—紫外检测(HPLC-UV)法测定峰面积,计算硝唑沙奈的体外累积释放度,并对释药模型进行拟合。【结果】硝唑沙奈及替唑尼特在2%CTAB0.1mol/mLHCl和2%CTAB磷酸盐缓冲液(pH6.8)两种介质中的理论塔板数均大于3000,分离度均大于2.0。精密度试验、重复性试验、稳定性试验、回收率试验、释放度均一性试验等均表明,HPLC-UV法适用于硝唑沙奈肠溶缓释颗粒体外释放度的测定。硝唑沙奈肠溶缓释颗粒在前2h内的累积释放量<10.0%,至24h时释放度大于90.0%,符合药品释放度检测要求。硝唑沙奈肠溶缓释颗粒体外释放的最佳拟合模型为Higuchi模型。【结论】HPLC-UV法是测定硝唑沙奈肠溶缓释颗粒体外释放度的有效方法,具有准确可靠、重复性良好、回收率高的特点。[Objective]The dissolution of nitazoxanide enteric sustained-release particle was determined to provide references for its quality control and treatment improvement. [Method]Release tests were carried out using rotating basket method [rotating speed ：75 r/min, temperature （37±0.5）℃ ,750 mL 0.1 mol/mL hydrochloric acid solution （containing 2% eetyl trimethyl ammonium bromide） for the initial 2 h, 250 mL 0.2 mol/mL sodium phosphate solution （containing 2% CTAB）, pH 6.8, total volume 1000 mL] Peak area of the samples collected at differenl time was measured using HPLC- UV, and then the external accunmlative release rate of nitazoxanide was calculated, finally the drug release model was fit- ted. [Result ]Number of theoretical plates of nitazoxanide and tizoxanide was over 3000 in 2% CTAB 0.1 mol/mL HC1 and 2% CTAB phosphate buffer （pH 6.8）, and their resolution was more than 2.0. The experiments of precision, repetition, stability, recovery and release proved that HPLC-UV was suitable for the detection of nitazoxauide enteric sustained-re- lease particle. The accumulated resolution of nitazoxanide enteric sustained-release particle in 2 h was less than 10.0%, and in 2-22 h, more than 90.0%, which accorded with the requirements of dl^ag release rate. Higuchi model was found to be the best fitting model. [Conclusion]Due to its accuracy, repeatability and high recovery, HPLC-UV was the effective method for determining the release rate of nitazoxanide enteric sustained-release particle.

关 键 词：硝唑沙奈 肠溶缓释颗粒 释放度 高效液相色谱-紫外检测法 Higuchi模型 

分 类 号：S859.7[农业科学—临床兽医学]