白藜芦醇眼用纳米乳-离子敏感型原位凝胶的制备与质量评价  

Preparation and Quality Evaluation of Resveratrol Ophthalmic Nanoemulsion-ion Sensitive in Situ Gel

作　　者：何朝星[1] 王欣 高淑颖[1] 贾佳 王晓晖[1] 敦洁宁[1] 杜青[1] HE Chao-xing;WANG-Xin;GAO Shu-ying;JIA-Jia;WANG Xiao-hui;DUN Jie-ning;DU Qing(School of Pharmacy,Hebei Medical University,Shijiazhuang 050017,China;Department of Pharmacy,The Third Hospital of Hebei Medical University,Shijiazhuang 050000,China)

机构地区：[1]河北医科大学药学院,石家庄050017 [2]河北医科大学第三医院药学部,石家庄050000

出　　处：《中国药学杂志》2022年第2期124-131,共8页Chinese Pharmaceutical Journal

基　　金：河北省自然科学基金项目资助(H2018206052,H2020206451);河北省2021年度医学科学研究课题资助(20211108)。

摘　　要：目的制备白藜芦醇眼用纳米乳-离子敏感型原位凝胶,并对其进行质量评价。方法通过测定药物在各相中的溶解度和绘制伪三元相图,筛选最优处方制备纳米乳。选择合适的结冷胶浓度和用量,制备离子敏感型原位凝胶,并对其pH、粒径、黏度、稳定性及含量进行测定。采用无膜法考察原位凝胶的溶蚀和释放行为,Franz扩散池法考察原位凝胶在角膜、巩膜、模拟结膜部位的累积渗透量。以家兔为实验动物,考察玻璃体内的药物蓄积以及对眼部刺激情况。结果制备的白藜芦醇眼用纳米乳-原位凝胶pH为(5.29±0.01),生理状态下粒径为(16.24±0.13)nm,与非生理状态无明显变化;生理状态下黏度升高明显,胶凝性能良好,稳定性良好;释药模型符合Higuchi方程,其释药机制以扩散为主;给药48 h后,在角膜、巩膜和模拟结膜的累积渗透率分别达到50%、67%和71%。家兔玻璃体中有一定的药物蓄积,对眼睛无刺激。结论制备的白藜芦醇眼用纳米乳-离子敏感型原位凝胶在生理条件下能迅速胶凝,稳定性好,释药持久,有一定量的药物可以到达眼后段,对眼睛无刺激,具有应用前景。OBJECTIVE To prepare resveratrol nanoemulsion-ion sensitive in situ gel and evaluate its quality. METHODS Firstly, by measuring the solubility of the drug in each phase and drawing the pseudo-ternary phase diagram, the optimal formulation was selected to prepare the nanoemulsion, and then ion-sensitive in situ gel was prepared by selecting appropriate concentration and amount of gellan gel. The pH, particle size, viscosity, stability and content of resveratrol nanoemulsion-ion sensitive in situ gel were investigated. The erosion and release behavior of in situ gel were evaluated by membrane-free method. Franz diffusion cell method was used to study the cumulative permeability of in situ gel in cornea, sclera and simulated conjunctiva.The drug accumulation in vitreous body and ocular irritation were investigated in rabbits. RESULTS The pH of the prepared ion-sensitive in situ gel was 5.29±0.01. Under physiological condition, the particle size was(16.24±0.13)nm, which had no significant change from that under non-physiological condition. The viscosity increased obviously in physiological state and the cementitious property was good.In situ gel had good stability. The drug release model fitted with Higuchi equation, and the drug release mechanism was mainly diffusion.The cumulative permeability of cornea, sclera and simulated conjunctiva reached 50%, 67% and 71%, respectively, at 48 hours after administration.There was a certain amount of drug accumulation in the vitreous of rabbits. It was non-irritating to the eyes. CONCLUSION The prepared ion-sensitive in situ gel could quickly gel under physiological conditions, which had good stability and sustained drug release. A certain amount of drugs could reach the posterior segment of the eyes without irritation to the eyes. It have application prospects.

关 键 词：白藜芦醇 纳米乳 离子敏感型原位凝胶 释放度 渗透性 刺激性 

分 类 号：R944[医药卫生—药剂学]