栀子苷立方液晶凝胶的制备、表征及体外评价

Preparation,characterization,and in vitro evaluation of geniposide cubic liquid crystal gel

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.