复方孕二烯酮阴道环的制备及体外释放

Preparation and in vitro release of the compound gestodene intravaginal ring

目的:研制复方孕二烯酮阴道环,并考察其体外释放度。方法:首先将2种药物分别制备成以PVPK30为载体的固体分散体,然后以硅橡胶为载体,采用热压硫化法,以两段结合式制备阴道环药芯,并包覆一定厚度的无活性硅橡胶膜,制得复方孕二烯酮阴道环。采用单因素考察方法对阴道环制备工艺及处方进行优化。以200 ml pH4.0磷酸盐缓冲液为释放介质,采用高效液相色谱法考察阴道环的体外释放度,并对其进行释放拟合。结果:通过优化确定最佳复方孕二烯酮阴道环制备工艺及处方,阴道环中药物可以维持21 d缓慢释放,释药速率符合Higuchi方程。结论:复方孕二烯酮阴道环具有良好的释药特性,制备工艺稳定;采用高效液相色谱法考察阴道环的体外释放度方便、快速和准确。

OBJECTIVE To prepare and investigate the in vitro release of the compound intravaginal ring （IVR） containing gestodene and ethinylestradiol. METHODS The solid dispersion of gestodene and ethinylestradiol was prepared respectively with PVPk30 as a carrier. The intravaginal ring was prepared by the method of hot pressing vulcanization with silicone elastomer as a carrier. The inner layer of the intravaginal ring contained two parts of fractional segment cores containing gestodene and ethinylestradiol respectively, which were separated by two parts of blank silicone elastomer, and the outer layer was a nonmedicated silicon rubber membrane. The preparation process and prescription of the vaginal ring were optimized using the method of single factor investigation. In vitro drug release test was conducted in a dissolution apparatus, release medium was 200 ml PBS（pH 4. 0） meeting with sink conditions, and release samples were determined by the high performance liquid chro- matography method. RESULTS This paper found the optimum preparation process and prescription of the vaginal ring by the optimizing tests. The intravaginal ring exhibited sustained release characteristics in vitro in 21 days, and the cumulative release of gestodene and ethinylestradiol were both fitted to Higuchi releasing equations. CONCLUSION The compound intravaginal ring exhibited a satisfied characteristics of release in＇vitro, and the preparation method was stable. The developed HPLC meth- od was convenient, rapid and accurate.