摘要
目的为促进水溶性栀子苷的透皮性能而制备栀子苷立方液晶凝胶(geniposide cubic liquid crystal gel,GE-CLC-G),并对其进行表征及体外评价。方法以甘油单油酸酯(glyceryl monooleate,GMO)为基质材料,采用注入法制备GE-CLC-G,通过三元相图筛选出空白立方液晶区域;采用单因素法优选GE-CLC-G的处方及工艺条件;建立栀子苷的HPLC含量测定方法;采用偏光显微镜(polarizing microscope,PLM)、小角X衍射仪(small angle X diffraction,SAXS)对产品进行表征;采用改良Franz扩散池,比较GE-CLC-G与栀子苷软膏的体外透皮特性;采用DHR-2流变仪,对比GE-CLC-G和栀子苷软膏的流变学性质。结果优选的GECLC-G处方及工艺为GMO∶无水乙醇∶水=64∶3∶33,1%栀子苷投药量,1%促渗剂(氮酮:丙二醇=1∶1),60℃涡旋3 min,25℃恒温箱密封、避光3 d。制得的GE-CLC-G为无色、澄明的凝胶状半固体;为立方相,其内部结构为双菱形(Pn3m)晶格;测得产品中栀子苷的含量为(9.94±0.02)mg/g,载药量较大,符合立方液晶的特点。含1%促渗剂的GE-CLC-G 24 h累积透皮率Q(%)和透皮速率常数Js明显高于不加促渗剂的栀子苷软膏和不加促渗剂的GE-CLC-G。流变学研究表明,GE-CLC-G属于非牛顿流体,生物黏附性好,结构更稳定。结论GE-CLC-G制备工艺简单,产品外观良好,PLM和SAXS可用于表征立方液晶凝胶,含量测定方法操作简单,专属性好;GE-CLC-G的体外透皮性能和流变学性质均明显优于栀子苷软膏。
Objective To prepare geniposide cubic liquid crystal gel(GE-CLC-G)and characterize and evaluate it in vitro,so as to enhance the transdermal performance of the water-soluble geniposide(GE).Methods Glyceryl monooleate(GMO)was used as the substrate material to prepare GE-CLC-G by injection method;the blank cubic crystal area was screened out by ternary phase diagram;the prescription and process conditions of GE-CLC-G were optimized by single factor method;the HPLC method for the determination of GE content was established.The product was characterized by polarizing microscope(PLM)and small angle X diffraction(SAXS).Modified Franz diffusion cell was used to compare the in vitro transdermal properties of GE-CLC-G and GE ointment,and DHR-2 rheometer was adopted to compare the rheological properties of GE-CLC-G and GE ointment.Results The optimal prescription and process of GE-CLC-G were as follows:GMO:anhydrous ethanol∶water=64∶3∶33,1% GE dosage,1% penetration enhancer(azone∶propylene glycol=1∶1),vortex at 60℃ for 3 min,sealed and avoiding light in a constant temperature box at 25℃ for 3 d.The obtained GE-CLC-G was colorless and clarified gel-like semi-solid;it was a cubic phase and its internal structure was a double diamond(Pn3m)lattice;the content of GE in the measured product was(9.94±0.02)mg/g,with a large drug load,which corresponded with the characteristics of cubic liquid crystal.The 24 h cumulative transdermal rate Q(%)and transdermal rate constant Js of GE-CLC-G containing 1% penetration enhancer were significantly higher than those of GE ointment and GE-CLC-G without penetration enhancer.Rheological studies showed that GE-CLC-G was a non-Newtonian fluid,with good bioadhesion and more stable structure.Conclusion The preparation process of GE-CLC-G is simple,the product appearance is fine;PLM and SAXS can be used to characterize cubic liquid crystal gel,and the content determination method is easy to operate,with good exclusiveness;the in vitro transdermal performance and rheological properties of GE-CLC-G are significantly better than GE ointment.
作者
欧阳威
黄星雨
王旭易
骆慧婷
李爽
谭颖
颜红
OUYANG Wei;HUANG Xingyu;WANG Xuyi;LUO Huiting;LI Shuang;TAN Ying;YAN Hong(Hunan University of Chinese Medicine,Changsha,Hunan 410208,China;Gongyi People's Hospital,Zhengzhou,Henan 451200,China)
出处
《湖南中医药大学学报》
CAS
2024年第1期38-46,共9页
Journal of Hunan University of Chinese Medicine
基金
湖南省自然科学基金面上项目(2022JJ30444)
湖南省中医药科研计划项目(2021223)
2022年湖南省研究生科研创新项目(CX20220791)
湖南中医药大学重点学科中药学科(校行发规字﹝2023﹞2号)。
关键词
立方液晶凝胶
栀子苷
三元相图
体外透皮
流变学
cubic liquid crystal gel
geniposide
ternary phase diagram
in vitro transdermal
作者简介
通信作者:颜红,女,博士,副教授,硕士研究生导师,E-mail:yh8632@126.com。
