复方炔诺酮片的溶出度测定方法研究及质量评价

Quality Evaluation and Study of Dissolution Determination for Compound Norethisterone Tablet

目的:通过研究国内不同企业不同批次的复方炔诺酮片的体外溶出度以评价其内在质量差别,从而为完善药典相关标准和为药品生产企业优化生产工艺提供参考。方法:采用正交试验对该制剂的溶出条件进行筛选,通过考察转速、取样时间和溶出介质3个因素,最终确定采用小杯法,以0.5%十二烷基硫酸钠为溶出介质,转速50 r/min、45 min取样测定。并采用高效液相色谱法同时测定其中炔诺酮和炔雌醇的体外溶出度,进而采用两条溶出曲线相似性的参数评价法(AV值法)考察两家国内生产企业8批产品溶出曲线的相似性。结果:由其溶出曲线和AV值法评价结果可见,两家国内生产企业8批复方炔诺酮片中炔诺酮在不同时间点的累积溶出度无显著差异,整体相似度较高;但炔雌醇在不同时间点的累积溶出度存在一定的差异,整体相似度较低。结论:复方炔诺酮片溶出曲线的差异可能会对药物的疗效造成一定影响,应对国内该制剂生产工艺和质量加强管理。同时,该制剂现行溶出度测定标准方法对产品质量区分力弱,亟待完善与提高。

OBJECTIVE： To evaluate the inherent quality differences of different batches of Compound norethisterone tablet from different domestic enterprises by researching its in vitro dissolution, to provide reference for improving relevant standards in pharmacopoeia and optimizing production processes in drug manufacturers. METHODS： Orthogonal test was adopted to screen its dissolving conditions, small glass method was finally confirmed by detecting rotating speed, sampling time and dissolution medi- um, sampling determination was conducted with the dissolution medium of 0.5% sodium dodecyl sulfonate and rotating speed of 50 r/min and 45 min. And HPLC was adopted to simultaneously determine the in vitro dissolution of norethindrone and ethinyl estra- diol, then AV value method was adopted to detect the similarity of dissolution profiles of 8 batches of products from 2 domestic en- terprises. RESULTS： The dissolution profiles and similarity of AV value method showed the cumulative dissolution of 8 batches of Compound norethisterone tablet from 2 domestic enterprises had no significant difference at different time points, overall similarity was relatively high; but the ethinyl estradiol had certain difference, overall similarity was relatively low. CONCLUSIONS： The dif- ference of dissolution profiles of Compound norethisterone tablet may has effect on the drug efficacy, the production process and quality in domestic enterprises should be managed strictly. Meanwhile, the current method of dissolution is weak to distinguish from the quality, which needs to be improved urgently.