吴茱萸碱超分子复合物的制备及体外溶出  

Process optimization and dissolution kinetics of evodiamine supra-structure complex

作　　者：柳珊[1] 谭群友[2] 尹华峰[1] 吴建勇[1] 张景勍[1] 

机构地区：[1]重庆医科大学药物高校工程研究中心和生物化学与分子药理学重点实验室,重庆400016 [2]第三军医大学大坪医院野战外科研究所胸外科,重庆400042

出　　处：《中国医院药学杂志》2012年第14期1088-1093,共6页Chinese Journal of Hospital Pharmacy

基　　金：教育部博士点基金资助项目(编号:20095503120008);重庆市教育委员会资助项目(首批高等学校优秀人才资助;编号:KJ090308)

摘　　要：目的:制备吴茱萸碱超分子复合物(EVO-PLC),并考察其体外溶出。方法:以吴茱萸碱(EVO)和磷脂的复合率为评价指标,通过单因素试验优化磷脂复合物的制备工艺。采用薄层色谱法,紫外光谱法验证磷脂复合物的形成,并测定其粒径和Zeta电位。用Weibull模型拟合法和相似因子(f2)法考察磷脂复合物的体外溶出动力学。结果:超分子磷脂复合物的最佳制备工艺为:以四氢呋喃为反应溶剂,磷脂与吴茱萸碱的物质的量的比为2∶1,吴茱萸碱的反应浓度为1.5 mg·mL-1,反应温度为60℃,反应时间为3 h;最优工艺的复合率为(92.01±0.11)%,粒径为(248.03±9.15)nm,Zeta电位为(-24.68±3.97)mV;薄层色谱法提示吴茱萸碱与磷脂复合过程中没有生成新物质;紫外光谱法提示吴茱萸碱与磷脂之间存在相互作用,而非简单的物理混合,溶出动力学结果表明吴茱萸碱磷脂复合物的溶出符合Weibull模型,相似因子(f2)法结果表明EVO通过与磷脂复合促进了EVO的体外溶出。结论:本文制备得到了工艺简单、复合率较高的吴茱萸碱超分子磷脂复合物,通过制备磷脂复合物大大增加了吴茱萸碱的体外溶出。OBJECTIVE To prepare evodiamine supra structure complex and investigate its dissolution kinetics. METHODS The evodiamine supra structure complex was prepared by solvent evaporation method, and optimized by one-factor experimental design with complex rate as the evaluation index. Particle size and Zeta potential of the optimal formulation were determined by photon correlation spectroscopy. Thin-layer chromatography （TLC） and ultraviolet spectroscopy were applied to verify the for- mation of supra structure complex. Dissolution behavior of the complex was studied by Weibull model and similarity factor f2.RESULTS The optimal process parameters were as follows： tetrahydrofuran was taken as the reaction solvent and values for phospholipids-to-evodiamine ratio, reaction concentration of evodiamine, reaction temperature and reaction time were 2：1, 1.5 mg.mL 1, 60 ℃ and 3 h, respectively. Complex rate of the optimal formulation was（92. 01 ± 0. 11 ] %, particle size and Zeta potential were（248. 03 ± 9. 15） nm and （ - 24. 68 ± 3.97） mV, respectively. Results of TLC and ultraviolet spectroscopy showed that interaction existed between evodiamine and phospholipids, but not forming a new compound. Dissolution kinetics of evodiamine was accorded with Weibull model. Results of similarity factor f2 indicated that dissolution of evodiamine was en- hanced by the formation of evodiamine complex. CONCLUSION Evodiamine supra structure complex with high complex rate was successfully prepared, and dissolution of evodiamine was markedly enhanced.

关 键 词：吴茱萸碱 磷脂复合物 溶出 威布尔模型 

分 类 号：R285.5[医药卫生—中药学]