多奈哌齐纳米混悬复合凝胶剂的制备及评价  

Preparation and Evaluation of Donepezil Nanosuspension Composite Gel

作　　者：崔楠 王琳琳 杨芸 王爱萍[1] CUI Nan;WANG Linlin;YANG Yun;WANG Aiping(School of Pharmacy,Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University),Ministry of Education,Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong,Yantai University,Yantai 264005,China;Department of Food Engineering,Shandong Business Institute,Yantai 264670,China;National Key Laboratory of Advanced Drug Delivery and Release Systems,Novapath Pharma(Chengdu)Co.,Ltd.,Chengdu 610200,China;Shandong Luye Pharmaceutical Co.,Ltd.,Yantai 264003,China)

机构地区：[1]烟台大学药学院,分子药理和药物评价教育部重点实验室(烟台大学),新型制剂与生物技术药物研究山东省高校协同创新中心,山东烟台264005 [2]山东商务职业学院,粮油食品学院,山东烟台264670 [3]诺桥制药(成都)有限责任公司先进药物递释系统全国重点实验室,四川成都610200 [4]山东绿叶制药有限公司,山东烟台264003

出　　处：《烟台大学学报(自然科学与工程版)》2025年第2期224-232,共9页Journal of Yantai University(Natural Science and Engineering Edition)

基　　金：山东省自然科学基金资助项目(ZR2022MH260)。

摘　　要：为了实现多奈哌齐(DPZ)的长效缓释,采用介质研磨法制备多奈哌齐纳米混悬剂(DPZ-NS),并将其与不同高分子材料/泊洛沙姆复合温敏凝胶混合以获得多奈哌齐纳米混悬复合凝胶剂(DPZ-NS-gel-PM)。以胶凝温度、黏度、体外释放和体外降解等为评价指标,对高分子材料种类(季铵化壳聚糖、海藻酸钠及羟丙基甲基纤维素(HPMC))及用量进行筛选,并对优化后的制剂进行体内外评价。结果显示,含0.5%HPMC的DPZ-NS-gel-HPMC缓释效果最佳,这可能是由于HPMC与凝胶基质产生较强的氢键作用,其胶凝温度为(32.2±0.2)℃,黏度为(163.2±1.3)mPa·s,药物释放和凝胶降解之间呈线性关系,在大鼠体内可缓释药物20 d,且具有良好的组织安全性。该制剂具有较好的长效缓释特性和应用前景。To achieve sustained-release of donepezil(DPZ),this study prepared donepezil nanosuspension(DPZ-NS)using wet medium grinding,and then mixed it with different polymers/poloxamer composite thermosensitive gels to obtain donepezil nanosuspension composite gels(DPZ-NS-gel-PM).Gelation temperature,viscosity,in vitro release,and in vitro degradation were used as evaluation indicators to screen the types(hydroxypropyltrimethyl ammonium chloride chitosan,sodium alginate,and hydroxypropyl methylcellulose(HPMC))and contents of polymers.The optimized formulation was then evaluated both in vitro and in vivo.The results showed that the DPZ-NS-gel-HPMC with 0.5%HPMC had the best sustained-release effect,possibly due to the strong hydrogen bonding interaction between HPMC and the gel matrix.Its gelation temperature was(32.2±0.2)℃,and the viscosity was(163.2±1.3)mPa·s.There was a linear relationship between drug release and gel degradation.The formulation achieved sustained release of the drug for 20 days in rats and exhibited good tissue safety.This formulation has good long-acting sustained-release properties and promising application prospects.

关 键 词：多奈哌齐 纳米混悬剂 凝胶 羟丙基甲基纤维素 缓释 

分 类 号：R944[医药卫生—药剂学]