甲硝唑阴道凝胶体外释放及透皮吸收研究

Study on in Vitro Release and Percutaneous Permeability of Metronidazole Vaginal Gel

目的 分别采用人工膜和小型猪皮作为体外释放和透皮吸收试验模型,评价甲硝唑阴道凝胶自研制剂与参比制剂的体外释放和透皮吸收效果的一致性。方法 采用HPLC法测定在不同时间取样的接收液中甲硝唑的浓度,计算累积透过量和透过率,采用中位体外释放比较法评价释放结果,采用双向双侧t检验和平均渗透率评价透皮吸收结果。结果 三批自研制剂与参比制剂的中位体外释放率比值的90%置信区间分别为0.96 ~ 1.22、0.92 ~ 1.16、0.99 ~ 1.11;三批自研制剂和参比制剂12h平均渗透率之比分别为:0.99、1.05和1.04,累积透过量经双向双侧t检验评价,t值分别为0.9799、0.929 和0.9989,且P>0.05。结论 甲硝唑阴道凝胶自制品和市售参比制剂的体外释放和透皮吸收效果一致。

Objective This study used artificial membrane and mini-pig skin as in vitro release and transdermal test model,respectively,to evaluate the consistency of the in vitro release and transdermal absorption effect of metronidazole vaginal gel self-developed preparations and the reference preparation.Methods The concentration of metronidazole in the transdermal receiving solution sampled at different times was determined by HPLC (high performance liquid chromatography),and the cumulative penetration amount and penetration rate of metronidazole was calculated.The release results were evaluated by the median in vitro release comparative evaluation method,and the results of transdermal absorption were evaluated by Two-sided t-test and the average penetration rate determination method.Results The 90% confidence intervals of the ratio of the median in vitro release rate of the three batches of self-developed preparations to the median in vitro release rate of commercial reference preparations are 0.96 ~ 1.22,0.92 ~ 1.16,0.99 ~ 1.11 respectively,The 12-hour average permeability ratios of the three batches of self-developed preparations and the reference preparations are 0.99,1.05,1.04 respectively,and cumulative permeations were tested by Two-sided t-test,the t-value were 0.9799,0.929,0.998 9,and P>0.05.Conclusion The self-developed metronidazole vaginal gel has the same effect of the in vitro release and transdermal absorption with the commercial reference preparation.