4个厂家甲睾酮片体外溶出度的比较

Comparation of dissolution rate of Methyltestosterone Tablets from 4 pharmaceutical factories

目的建立甲睾酮片溶出度的HPLC测定方法 ,比较4个厂家甲睾酮片在4种不同溶出介质中的溶出曲线,对全国范围市售的甲睾酮片溶出度质量进行合理分析。方法采用美国FDA推荐的4种溶出介质(水、pH 4.5磷酸盐缓冲液、pH 6.8磷酸盐缓冲液、pH 1.0盐酸溶液)比较4个厂家甲睾酮片的溶出曲线,通过考察在同一种溶出介质中不同厂家样品的溶出曲线,筛选能区分各厂家样品溶出质量优劣的溶出条件;通过比较同一厂家在4种不同溶出介质中的溶出曲线,对各厂家的甲睾酮片的产品质量进行区分,筛选工艺稳定、质量优良、适宜病人服用的产品。设定其中1个厂家(厂家D)的样品作为参考制剂,其余3个厂家的样品作为受试制剂,进行溶出曲线的比较,用AV法考察参考制剂与受试制剂溶出曲线的相似性。结果 4个厂家的甲睾酮片均符合《中国药典》(2010版)标准中规定的溶出度要求,但在4种溶出介质中的溶出曲线存在差异,只有厂家D生产的甲睾酮片具有"非pH依赖性",其余3个厂家的产品(除厂家C的一个批号产品)与之均不相似。结论建立的溶出度测定方法能有效区分不同厂家的甲睾酮片溶出情况,不同厂家的甲睾酮片产品质量有区别,建议临床使用时加以注意。关键词:甲睾酮片;溶出曲线;

OBJECTIVE To establish a determination method by HPLC of dissolution rate of Methyltestosterone tablets and compare the in vitro dissolution of Methyltestosterone tablets from 4 different pharmaceutical factories. METHODS The dissolution profiles of Methyltestosterone tablets from 4 pharmaceutical factories were investigated in phosphate buffer solution （ pH = 4. 5 and pH = 6. 8 ）, water and hydrochloric acid （ pH = 1.0） recommended by FDA,in order to choose the proper dissolution medium, the different dissolution profiles of 4 factories in the same medium were investigated. According to compare the different dissolution profiles of the product got from the same factory in 4 dissolution mediums, product which was suit the needs of the different patients were chosen, the similarity between the reference preparation and test preparation were investigated by calculating AV values. RESULTS The in vitro dissolution of Methyltestosterone tablets from 4 different pharmaceutical factories all fulfilled the requirements of Chinese Pharmacopoeia （2010 edition） ,but the differences of dissolution profiles were found among the Methyltes- tosterone tablets. Only the product of factory D was independent with the pH of dissolution medium and the ones of the other 3 factories were not similar with it accept one product of factory C. CONCLUSION The dissolution of Methyltestosterone tablets from 4 pharmaceutical factories in different medium are different. There is significant differ- ence among the quality of Methyltestosterone tablets from 4 pharmaceutical factories,which should be paid attention in clinical application.