中药提取物葫芦素B-PLGA微球的制备及处方工艺优化

目的:制备中药提取物葫芦素(Cuc)B-乳酸-羟基乙酸共聚物(PLGA)微球。方法:应用改良的乳化溶剂挥发法制备微球;采用星点设计-效应面法优化制备工艺,以聚乙烯醇(PVA)浓度和投药比为自变量,微球的产率(Y1)、载药量(Y2)、包封率(Y3)、粒径(Y4)、24h累积释放量(Y5)为指标,进行多元线性回归和二次多项式拟合;改良的直接释药法考察微球的体外释放情况。结果:Y1、Y2、Y3、Y4、Y5二次多项式方程拟合效果较好,较优的工艺条件为PVA浓度0.014,投药比0.066 5。制得的微球形态圆整,Y1、Y2、Y3、Y4、Y5分别为79.9%、7.83%、80.5%、56.18μm、6.98%。体外释放35d的累积释放量为86.73%。结论:制备的CucB-PLGA微球满足了长效缓释的要求,所建立的模型预测性良好。

Preparation and Optimization of Formulation of PLGA Microspheres Containing Chinese Herbal Extract Cucurbitacin B

OBJECTIVE： To prepare Polylactic- co-glycolic acid） （PLGA） microspheres loaded with Chinese herbal extract cucurbitacin B. METHODS： Cucurbitacin B loaded by PLGA microspheres were prepared by modified emulsification- solvent evaporation method. Central composite design - response surface method was applied to optimize the formulation with PVA concentration and ratio of drug to polymer as independent variables, and with yield of microspheres（Y1）, drug loading amount （Y2）, encapsulation efficiency （Y3）, mean particle diameter （Y4）, and the cumulative percentage of the drug release in 24 hr（Y5） as indexes to conduct multiple linear regression and second - order polynomial equation fitting. In vitro release test was performed by modified immediate release method. RESULTS： The results showed that all response variables were greatly fitted by a second- order polynomial equation. The optimal formulation was proved to be as follows： PVA concentration was 0.014 and ratio of drug to polymer was 0.066 5. The microspheres prepared in the optimal formulation were spherical and had smooth surface. Y1, Y2, Y3, Y4, and Y5 were 79.9%, 7.83%, 80.5%, 56.18 μm and 6.98%, respectively. The cumulative release from microspheres within 35 days reached 86.73%. CONCLUSION： Cucurbitacin B- PLGA microspheres are characterized by prolonged action and sustained-release. Furthermore, the established model has satisfactory predictability.