星点设计-效应面法优化流化床制备盐酸普萘洛尔微囊工艺

Optimization Preparation of Propranolol Hydrochloride Microcapsules with Fluidized Bed by Central Composite Design and Response Surface Method

目的优化盐酸普萘洛尔微囊的制备工艺。方法采用流化床制备普萘洛尔微囊,以平均粒径,包封率、载药量及总评归一值为评价指标,并运用星点设计考察囊材液流速、喷雾压力对制备工艺的影响,对结果进行多元线性和二项式拟合,效应面法选取最佳工艺条件进行预测分析。结果从复相关系数上看,各指标二项式拟合方程均优于多元线性回归方程,最佳工艺参数:囊材液流速1.00 mL·min-1,喷雾压力0.65 bar,在此工艺条件下得到微囊粒径为300μm,载药量为20.54%,包封率达89.63%。结论优选普萘洛尔微囊的流化床制备工艺稳定可行,包封率高,有利于工业化生产。

OBJECTIVE To optimize the formulation of propranolol hydrochloride microcapsules. METHODS Propranolol hydrochloride microcapsules were prepared by fluidized bed. The effects of influence factors such as the flow rate of capsule material solution and spray pressure, on mean diameter, entrapment efficiency, drug loading and overall desirability were investigated by using central composite design and response surface method. The data were imitated using multi-linear equation and second-order polynomial equation. RESULTS The latter was prior to the former considering from multiple correlation coefficients. The best process conditions were as follows： the flow rate of capsule material solution of 1.00 mL＇min-1 and spray pressure of 0.65 bar. Under the optimal conditions, the mean diameter, entrapment efficiency, drug loading of the propranolol hydrochloride microcapsules were 300 μm, 20.54% and 89.63%. CONCLUSION The optimized preparation technique for the propranolol hydrochloride microcapsules with fluidized bed is stable, feasible, with high entrapment efficiency. It can be used for the industrial manufacture.