目的 探索应用改良Weibull拟合参数法评估药物平均溶出/释放曲线的相似度。方法 选取3种代表药品,使用光纤药物溶出度实时测定仪,分别在线监测各批药品参比与受试制剂随时间变化的药物累积溶出/释放百分率,计算各药品参比与受试制剂不同时刻药物平均累积溶出/释放百分率并描绘药物溶出/释放曲线;采用改良Weibull模型拟合时间-药物平均累积溶出/释放百分率数据,并提取拟合参数c、Ti、b、a及其95%的置信区间。观察受试与参比或参照制剂实际平均溶出曲线的变异,以及采用改良Weibull拟合参数法评估受试与参比或参照制剂平均溶出曲线的相似度。结果 实验用缓释制剂的药物平均累积释放百分率经改良Weibull模型拟合后,受试与参比或参照制剂相应的拟合参数无明显差异,两条溶出曲线相似度很高;实验用非修饰制剂,无论受试与参比制剂的剂型是否相同,它们的药物平均累积释放百分率经改良Weibull模型拟合后,受试与参比或参照制剂相应的拟合参数均存在不同程度的差异,受试与参比或参照制剂的溶出曲线相似度较低。结论 采用改良Weibull拟合参数法评估药物平均溶出/释放曲线的相似度,拟合优度好,可以量化。
Abstract
OBJECTIVE To evaluate the similarity of the mean drug dissolution or release curves by the experimental model of reformatory Weibull. METHODS Three drugs were taken as the model drugs. With the fiber-optic in site dissolution testing equipment(FODT),the percentages of accumulated dissolution/release changing with time of the control and test preparations of every drug were respectively monitored. The mean percentages were calculated and the dissolution/release curves were drawn. The data were fitted by the reformatory Weibull model. The fitted parameters c, Ti, b, a, and the 95% confidence intervals of every parameters were extracted. The similarity of the mean drug dissolution curves between the control and test preparations was evaluated by the fitted parameters and observation of the dissolution curves. RESULTS For the sustained-release preparations,there was no significant difference in the parameters c, Ti, b, and a of the test and control samples,and the mean drug release curves were similar. As for the non-modified preparations,whether the dosage forms of the test and control preparations were the same or not,there existed differences in the parameters fitted by the method of reformatory Weibull model. CONCLUSION The modified method of reformatory Weibull model can be applied in the evaluation of similarity of drug dissolution behavior with satisfactory goodness-of-fit and quantitative result.
关键词
药物平均溶出曲线 /
改良Weibull模型 /
拟合参数 /
相似度
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Key words
the curve of mean drug dissolution /
reformatory Weibull model /
fitted parameter /
similarity
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中图分类号：
R917
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参考文献
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脚注
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基金
新疆维吾尔自治区自然科学基金资助项目(2013211A119)
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