葛根素环糊精包合物脂质体的制备及体外性质研究

Preparation of Liposomes Encapsulating Puerarin-Cyclodextrin Complexes and Its Pharmaceutical Characteristics in Vitro

目的研究葛根素环糊精包合物脂质体的制备方法、筛选出其最优处方并对该处方进行质量研究及体外性质的考察。方法运用相溶解度法进行增溶实验,通过冷冻干燥法制备葛根素羟丙基-β-环糊精(HPCD)包合物;采用X射线衍射,差示扫描量热法,体外溶出度法对包合物进行了鉴定。用薄膜分散-冻融法将包合物制成脂质体;用正交实验优选处方;透射电镜观察形态;马尔文激光粒度仪测定粒径、Zeta电位;透析法结合高效液相色谱法测定包封率;动态透析法考察体外释药性质。结果制得的脂质体平均粒径为395.7 nm,表面电荷为-34.04 mV,包封率大于65%,稳定性好。药物体外释药遵循Higuchi方程:从拟合结果来看,脂质体溶液释药符合动力学方程:Q=12.711t1/2+7.090(r=0.983)。结论采用薄膜分散-冻融法,可制得具有较高包封率的葛根素环糊精包合物脂质体,脂质体具有良好的缓释效果,提高了药物在血浆中的稳定性。

OBJECTIVE To prepare liposomes encapsulating puerarin-hydroxypropropyl -β-cyclodextrin complexes, and screen the optimal formulation, and study its pharmaceutical characteristics in vitro. METHODS Phase solubility studies at pH values and physiologically acceptable HP-β-CD-concentrations were performed, and solubilized puerarin was quantified by HPLC. The puerarin- eyelodextrin indusion compound was prepared with lyophilization technique. The inclusion compound was identified by X-ray diffraction （XRD） and differential scanning calorimetry （DSC） methods and in vitro dissolution test. The liposomes encapsulating puerarin- cyclodextrin complexes were prepared by thin film method with freeze-thawing steps. Unloaded puerarin were separated by dialyzation. HPLC method was used to determine the encapsulation efficiency of liposomes encapsulating puerarin-cyctodextrin complexes. According to the entrapment efficiency, an optimal technique was chosen with orthogonal design. The shape, particle size and Zetapotential of the liposomes were investigated with transmission electron microscope and laser scatter. The release of puerarin from liposomes was studied in vitro. RESULTS The prepared liposomes demonstrated good stability and encapsulation efficiency was （68.10 ＋ 0. 7 ） % （ n = 3 ）. The average size was 395.7 nm and the Zeta potential of the modified liposomes was - 34. 04 mV. The release in vitro was characterized by Hignchi equation. ：Q = 12. 711t^1/2 ＋7. 090（r =0. 983）. CONCLUSION Thin film method with freeze-thawing steps could increase the entrapment efficiency of liposomes encapsulating puerarin-cyclodextrin complexes and the stability of liposomes in plasma. The in vitro release profile studies showed that the liposomes entrapment of inclusion complexes displayed slower release rate.