苍夷纳米乳原位凝胶的制备及体外鼻黏膜释药机制研究

Preparation of Cangyi nanoemulsion in situ gel and drug release mechanism of nasal mucosa in vitro

制备苍夷纳米乳原位凝胶并研究其体外鼻黏膜释药机制。对复方中不同饮片进行提取后,通过伪三元相图法确定纳米乳处方,分别以混合乳化剂与油相的比例[(S+COS)/O],混合乳化剂的比例(Km),水相与混合乳化剂和油相的比例[W/(S+COS+O)]为考察因素,以归一值(OD)为评价指标,利用星点设计-效应面法优化苍夷纳米乳处方;以泊洛沙姆407(P407)和泊洛沙姆188(P188)的比例为考察因素,以胶凝温度为评价指标,优化苍夷纳米乳原位凝胶处方。采用改良Franz扩散池法,以氧化苦参碱、阿魏酸、丹酚酸B含量为指标,研究苍夷纳米乳原位凝胶鼻黏膜释药机制。优选苍夷纳米乳原位凝胶处方组成蓖麻油聚烃氧酯(35)(EL-35)为6.862%,无水乙醇为4.262%,油酸乙酯为1.392%,P407为7%,P188为6%。其平均pH 5.55,平均胶凝温度32.8℃。体外释放研究表明氧化苦参碱、阿魏酸、丹酚酸B同步释放且释药行为均符合Higuchi模型。苍夷纳米乳原位凝胶制备工艺稳定,pH、胶凝温度、黏度适宜,具有一定缓释作用,可满足鼻腔局部用药需求。

To prepare Cangyi nanoemulsion in situ gel and study its nasal mucosa release mechanism in vitro.After proper treatment of different drugs in the compound,the prescription of nanoemulsion was determined by pseudo-ternary phase diagram method.With the ratio of mixed emulsifier to oil phase[(S+COS)/O],the ratio of mixed emulsifier(K_m),the ratio of water phase to mixed emulsifier and oil phase[W/(S+COS+O)]as investigation factors and the normalized value(OD)as evaluation index,the prescription of Cangyi nanoemulsion was optimized by central composite design-response surface method.With the ratio of poloxamer 407(P407)and poloxamer 188(P188)as the investigation factors and the gelation temperature as the evaluation index,the in situ gel prescription of Cangyi nanoemulsion was optimized.The improved Franz diffusion cell was used to explore the nasal mucosa drug-release mechanism of Cangyi nanoemulsion in situ gel with oxymatrine,ferulic acid and salvianolic acid B content as indexes.The optimal prescription of Cangyi nanoemulsion in situ gel was as follows:6.862%castor oil polyoxyl(EL),4.262%absolute ethanol,1.392%ethyl oleate,7%P407 and 6%P188.The average pH was 5.55 and the average gelation temperature was 32.8℃.In vitro release studies showed that oxymatrine,ferulic acid and salvianolic acid B were released simultaneously and the drug release behavior was consistent with that in Higuchi model.The preparation process of Cangyi nanoemulsion in situ gel is stable,with suitable pH value,gelation temperature and viscosity.It has a certain slow-release effect,and can meet the needs of local nasal drug use.