高载药量萘普生微乳凝胶的制备及离体经皮渗透性能研究  

Preparation of Naproxen Microemulsion-Gel with High Drug Content and Investigation of Its in Vitro Transdermal Delivery Ability

作　　者：钟华[1] 徐珍[1] 段海龙[2] 张星星[1] 韩建勇[1] 田青平[1] 

机构地区：[1]山西医科大学药学院,太原030001 [2]太原工业学院化学与化工学院,太原030008

出　　处：《中国药学杂志》2012年第12期970-975,共6页Chinese Pharmaceutical Journal

基　　金：山西医科大学博士启动基金资助

摘　　要：目的制备载药量高、黏附性好的萘普生微乳凝胶,并考察其经皮渗透性能。方法通过伪三元相图确定以Tween80和Tween20的混合物为乳化剂、卡必醇为助表面活性剂、薄荷油为油相的微乳区域;用相转变温度法制备载药微乳,将卡波姆980直接加入微乳中制备萘普生微乳凝胶;用药物透皮扩散仪考察制剂的离体经皮渗透性能;用光散射粒度仪测定微乳粒径,电子透射电镜观察制剂的微观形态。结果 Tween80-Tween20质量比为2∶1,乳化剂与助乳化剂之比为3∶1时,形成的微乳区域最大;优化微乳载体处方为:薄荷油5%、乳化剂35%、水60%,其载药量可达4%,经离体鼠皮的稳态渗透速率(Js)为(531.912±1.3)μg.cm-2.h-1,符合微乳特征;加入2.5%的卡波姆980制得外观均匀、透明的微乳凝胶,黏度由104.5mPa.s增加到18.9 Pa.s,兼具微乳和凝胶的微观特性,Js为(640.327±0.7)μg.cm-2.h-1。结论以卡必醇为助表面活性剂所制的萘普生微乳凝胶黏附性好、促渗和增溶作用大,有望成为萘普生的新型给药制剂。OBJECTIVE To prepare naproxen microemulsion-gel with high drug content and adhesiveness,and investigate its in vitro transdermal delivery ability. METHODS The ranges of microemulsion with the mixture of Tween 80 and Tween 20 as surfactant,carbitol as cosurfactant,peponida as oil,were defined through construction of the pseudo-ternary phase diagrams.Drug-loaded microemulsions were prepared by phase transfer temperature method.Naproxen microemulsion-gel was prepared by directly adding carbomer 980 into its microemulsion.The diffusion studies of all formulations were performed using a drug diffusion apparatus.The mean droplet sizes of naproxen microemulsion were measured via dynamic light scattering（DLS） on a Zetasizer,their microstructures were observed by transmission electron microscope（TEM）. RESULTS Microemulsion range was largest when the mass ratio of Tween 80 and Tween 20 was 3：1,surfactant and cosurfactant was 2：1.While the microemulsion composed of 5% peponida,35% emulsifier and 60% water,drug loaded in microemulsion can attain 4%,which was accorded with the characterization of microemulsion.Adding 2.5% carbomer 980 into optimization microemulsion,even and transparence microemulsion-gel was obtained,which has the combination of o/w microstructure of microemulsion and the three-dimensional gel network of hydrogel.The viscosity of microemulsion-gel was increased from 104.5 mPa·s to 18.9 Pa·s,the steady-state permeation rates through excised cavia skin increased from（531.912±1.3） to（640.327±0.7）μg·cm-2·h-1. CONCLUSION Naproxen microemulsion-gels prepared by selected carbitol as cosurfactant can obtain high drug content and percutaneous absorbtion,exhibit favourable adhesiveness,which may be a promising new dosage form for transdermal delivery of naproxen.

关 键 词：高载药量 萘普生 微乳凝胶 经皮给药 卡必醇 

分 类 号：R944[医药卫生—药剂学]