双氯芬酸钾凝胶贴膏质量研究方法的建立和制剂评价

Establishment of the quality research method for diclofenac potassium cataplasms and the preparation evaluation

目的制备新型的双氯芬酸钾凝胶贴膏,建立质量研究方法,并进行贴剂质量评价。方法建立高效液相色谱法(HPLC),以十八烷基硅烷键合相硅胶为固定相;甲醇-4%冰醋酸溶液(80∶20,V/V)为流动相;检测波长276 nm。采用甲醇提取贴膏中双氯芬酸钾,并测定凝胶贴膏黏附性、双氯芬酸钾含量及含量均匀度;按《中华人民共和国药典》附录XD释放度测定法第四法测定凝胶贴膏释放度。结果贴膏初黏力平均最大钢球号为6号;在该色谱条件下,双氯芬酸钾在400~800μg/ml范围内线性良好,平均加样回收率为1.33%,精密度RSD均<1.93%(n=6)。释放度方法学研究表明在1~50μg/ml范围内线性良好,精密度和回收率符合《中国药典》要求。制备的贴膏经测定含量均匀度符合《中国药典》规定,在2、5和8 h的贴膏释放量分别为标示量的20%~45%,40%~80%和>70%,释放曲线遵循一级释药方程。结论建立的HPLC法灵敏、准确、操作简单、重现性好,可用于双氯芬酸钾凝胶贴膏的质量控制。制备的贴膏含量均匀,具有缓释释放特性,有望开发成为双氯芬酸钾新制剂。

Objective To prepare the new diclofenac potassium cataplasms,establish a quality research method and evaluate the preparation quality by the established method.Methods A high performance liquid chromatography(HPLC)was performed on an ODS column(the column temperature 35℃)using the methanol-4%glacial acetic acid solution(80∶20,V/V)as mobile phase,and the detection wavelength was set at 276 nm.Diclofenac potassium was extracted with methanol,and the adhesion,content and uni⁃formity of potassium diclofenac were measured.The release of diclofenac potassium from the cataplasms was determined in accordance with the fourth method of the XD release methods in the Appendix of the Chinese Pharmacopoeia.Results The average maximum number of steel ball stuck in the cataplasms in the initial adhesion test was No.6.Under the HPLC conditions,potassium diclofenac showed good linearity within the concentration range of 400-800μg/ml,with the average sample recovery rate 1.33%and RSD<1.93%(n=6).The methodological studies for the drug release test for the diclofenac potassium cataplasms showed that the diclofenac potassium showed a good linearity within the range of 1-50μg/ml in the drug release test,and the precision and recovery well satisfied the requirements of Pharmacopoeia.The content uniformity of the cataplasms was in accordance with the Pharmacopoeia.The release amounts of the cataplasms in 2,5 and 8 hours were 20%-45%,40%-80%and more than 70%of the labeled amount,respectively,and the release curve followed the first-order release equation.Conclusion The established HPLC method is sensitive,accurate,easily operable and reproducible,which could be used for the quality control of diclofenac potassium cataplasms.The prepared diclofe⁃nac potassium cataplasms were of uniform content and showed characteristics of the sustained release,which is expected to be devel⁃oped to a new preparation of diclofenac potassium.