甲硝唑口颊片的释放度测定及不同测定方法的结果比较

Determination of the release rate of metronidazole buccal tablets and the comparison of different methods

建立测定甲硝唑口颊片释放度的方法,并对不同装置不同厂家测定的释放曲线进行比较。分别采用新建立的流通池法、篮法以及原标准的小杯法考察甲硝唑口颊片的体外释放特性,在规定时间点取样后采用HPLC测定。对测定结果进行释药曲线的相似性分析和威布尔参数的统计学分析。甲硝唑在3.012.50.20μg/mL内线性关系良好(r=0.9999),样品溶液在24h内稳定。相同装置下,不同厂家释放曲线不相似。经Weibull方程拟合后,A厂样品在篮法和流通池法下,得到的特征溶出参数不存在显著性差异(P>0.05),B厂样品在不同装置下得到的特征溶出参数存在显著性差异(P<0.01)。不同厂家甲硝唑口颊片的释放特性存在明显差异,本研究所建流通池法和篮法均可用于甲硝唑口颊片的释放度检查,对完善甲硝唑口颊片的质量控制有指导意义。

To establish a method for determination of the release rate of metronidazole buccal tablets, and compare the release curves among different test methods and among different manufacturers. The newly established flow-through cell method, the basket method and the original small vessel method were employed to investigate the dissolution characteristics of all the samples, and the concentrations of each sampling point were determined by HPLC. The dissolution data were used to analyze the similarity of the release curves and statistical significance of Weibull parameters. The linear correlation of metronidazole was observed in the range of 3.012~50.20μg/mL (r =0.9999), and the sample solution was stable in 24h. With the same device, the drug release curves of different companies were not similar. The results of these methods were analyzed by the Weibull equation, and there was no significant difference in the characteristic dissolution parameters of samples from A manufacturer with the basket method and the flow-through method (P>0.05), but there was significant difference in the parameters of samples from B manufacturer (P<0.01). There was significant difference in dissolution parameters among the metronidazole buccal tablets from different manufacturers. These methods including the flow-through cell method and the basket method could both be used to determine the release of metronidazole buccal tablets. This study is of guiding significance to improve the quality control of metronidazole buccal tablets.