阿奇霉素缓释阴道栓的处方优化

目的:优化阿奇霉素缓释阴道栓的处方。方法:采用硬脂酸聚烃氧酯(S-40)为基质,以羟丙基甲基纤维素(HPMC)为缓释材料、甘油为保湿剂等制备阿奇霉素缓释阴道栓。以累积释药百分率和栓剂硬度为考察指标、8%HPMC和甘油在处方中的用量为考察因素,采用正交设计法进行处方优化,并进行验证试验及体外释药模型拟合。结果:优化后处方组成为阿奇霉素6g,8%HPMC23.52g,甘油29.40g,无水乙醇3g,尼泊金乙酯0.59g,S-40294g。由优化后处方制备的3批栓剂平均含量99.5%,硬度符合要求,体外释放重复性和均一性良好,180min时累积释药百分率均大于98%,体外释药动力学符合Higuchi方程。结论:优化后的阿奇霉素缓释阴道栓处方可行,制备工艺稳定,重复性好,符合缓释制剂要求。

Optimization of the Formulation of Azithromycin Sustained- release Vaginal Suppository

OBJECTIVE： To optimize the formulation of azithromycin sustained- release vaginal suppository（ASVS）. METHODS： The ASVS was prepared using S-40 as suppository base, HPMC as sustained- release material and glycerine as humectant. The formulation of ASVS was optimized by orthogonal design with accumulated release percentage and hardness as indexes and the amount of 8% HPMC and glycerol as factors; meanwhile, a verification test and the fitting of in vitro drug release model were performed. RESULTS： The optimized formulation ASVS was as follows： azithromycin 6 g, 8% HPMC 23.52 g ,glycerol 29.40 g, ethanol absolute 3 g, ethylparaben 0.59 g, and S- 40 294 g. Three batches of suppositories prepared under the optimized formulation reached a mean content of 99.5%, with hardness up to the standard, showing good reproducibility and homogenicity in drug release in vitro. The accumulative release rates of all samples were greater than 98% at 180 min, and the release dynamics in vitro were in line with Higuchi equations. CONCLUSION ： The optimized ASVS is feasible in formulation, stable and reproducible in preparation technology and up to the standard for sustained - release preparation.