纳美芬乳酸-羟乙酸共聚物缓释微球的制备

 目的使用星点设计-效应面法优化纳美芬乳酸-羟乙酸共聚物缓释微球的制备工艺,提高可预测性。方法微球用O/O型乳化溶剂挥发法制备,自变量为外相Span80浓度、内相乳酸-羟乙酸共聚物(PLGA)浓度和理论载药量,以微球载药量、包封率、平均粒径、跨距和第1天微球释药百分数(F_1d)为因变量对自变量的各水平进行多元线性回归和二项式拟合,根据因变量效应面法选取较佳工艺条件并于较优区进行预测分析。结果5个方程均采用二项式拟合的效果较好,选择的较佳工艺为Span80浓度1.5%、PLGA浓度175g.L^-1、理论载药量6%,按优化工艺制备的微球球形圆整,载药量、包封率、平均粒径、跨距和F_1d分别为4.37%,72.8%,64.1μm,1.36和8.93%,微球具有显著的体外缓释特性。结论星点设计-效应面法优化微球制备工艺预测性良好。

Preparation of Nalmefene Poly ( lactic-co-glycolic acid) Microspheres

OBJECTIVE To optimize the preparation of nalmefene poly(lactic-co-glycolic acid) microspheres by central composite design-response surface methodology,and to investigate its potential use in predictable preparation.METHODS Microspheres were prepared by O/O emulsification/solvent evaporation method. Effects of three independent variables i.e.,Span80 concentration in outer phase,poly(lactic-co-glycolic acid) concentration in inner phase and theoretical drug content,were evaluated with a number of response variables. Response variables were drug content,encapsulation efficiency,mean diameter,diameter span and the cumulative percentage of the drug released in the first day after incubation(F_1d). Multiple linear regression and second-order polynomial model were fitted to the data,and the resulting equations were used to produce five response surface graphs,by which optimal experimental conditions were selected. RESULTS All response variables were found to be greatly dependent on three independent variables,and the optimal conditions were Span80 concentration 1.5%,poly(lactic-co-glycolic acid) concentration 17.5%,and theoretical drug content 6%. According to the optimal conditions,the drug content,encapsulation efficiency,mean diameter,diameter span and F_1d of prepared microspheres were 4.37%,72.8%,64.1 μm,1.36 and 8.93%,respectively. CONCLUSION Central composite design-response surface methodology is successfully used to optimize the preparation of poly(lactic-co-glycolic acid) microspheres containing nalmefene.