易黄汤阴道用温敏原位凝胶及其普通凝胶的流变学和体外释放研究

Rheology and in vitro release properties of thermosensitive in situ gel of Yihuang Decoction and its common gel for vaginal use

评价易黄汤阴道用温敏原位凝胶及其普通凝胶的性状、流变学特性,并预测易黄汤原位凝胶的体内释放行为。以泊洛沙姆为材料制备易黄汤阴道用温敏原位凝胶,以卡波姆为材料制备其普通凝胶,对比2种凝胶经模拟阴道液稀释前后性状差异;采用安东帕MCR102流变仪,测定易黄汤原位凝胶和普通凝胶的流变学参数;并以盐酸小檗碱为指标成分,评价易黄汤温敏原位凝胶的体外释放性能。易黄汤阴道用温敏原位凝胶色黄、透明,低温条件下呈现流体性质,为牛顿流体;到达凝胶温度24.5℃后,以半固体性质为主,属于假塑性流体。模拟阴道给药条件后,预测凝胶温度为37℃,胶凝时间为30 s。而易黄汤普通凝胶的流变学性质不随温度变化而明显改变,且较原位凝胶而言,色深、半透明、模拟阴道给药后药物流动性较强。体外释放研究表明,易黄汤阴道用温敏原位凝胶中盐酸小檗碱累积释放动力学行为符合Higuchi方程。通过模拟阴道给药,运用物理性状和动态流变学参数,直观、科学地评价易黄汤阴道用温敏原位凝胶及其普通凝胶特性。研究发现温敏原位凝胶可快速贴附于阴道黏膜并释药,较普通凝胶更适合易黄汤阴道给药的剂型开发,为易黄汤新型阴道用制剂的研究提供参考依据。

To evaluate the traits and rheological properties of thermosensitive in situ gel of Yihuang Decoction and its common gel for vaginal use,and predict the release behavior of Yihuang Decoction in situ gel in vitro.Poloxamer was used as thermosensitive material to prepare Yihuang Decoction vaginal in situ gel,and Yihuang Decoction common gel was prepared with carbopol.Then the differences of the two gels before and after diluting with vaginal fluid were compared.The rheological parameters of Yihuang Decoction in situ gel and its common gel were determined with Anton Paar MCR102 rheometer.In addition,berberine hydrochloride was selected as an index component to evaluate the in vitro release properties of Yihuang Decoction vaginal thermosensitive in situ gel.Yihuang Decoction vaginal thermosensitive in situ gel was Newtonian fluid under low-temperature conditions,which was yellow and transparent.After reaching the gelling temperature of 24.5℃,it became semi-solid,pseudoplastic fluid.The gelling temperature was predicted to be 37℃,and the phase transition time was 30 s after diluting with simulated vaginal fluid.However,the rheological properties of Yihuang Decoction common gel had no significant changes with temperature.Compared with in situ gel,the color of common gel was darker and more translucent.Besides,its mobility was stronger after diluting with simulated vaginal fluid.The in vitro release study showed that the kinetic behavior of berberine hydrochloride in Yihuang Decoction vaginal thermosensitive in situ gel was matched with the Higuchi equation.Through simulation of vaginal administration,physical properties and dynamic rheological parameters were used to intuitively and scientifically evaluate the two gels.Compared with the common gel,the thermosensitive in situ gel could quickly attached to the vaginal mucosa and release drug,and thus was more suitable for developing vaginal administration of Yihuang Decoction,which also provides references for studying new vaginal preparation of Yihuang Decoction.