星点设计-效应面法优化盐酸普萘洛尔凝胶处方基质

Formulation Optimization of Propranolol Hydrochloride Gels by Central Composite Design-Response Surface Methodology

目的对盐酸普萘洛尔凝胶处方基质进行优化。方法在单因素实验的基础上,采用星点设计-效应面法,以处方中影响较为显著的甘油(A)、聚乙二醇-400(B)、羟丙甲纤维素(C)的加入量为考察因素,高效液相色谱法测定盐酸普萘洛尔8 h单位面积累积透过量为考察指标,用二次多项式模型描述考察指标和3个考察因素之间的数学关系,绘制效应面和等高线图,确定较优处方基质并进行验证。结果优选的基质处方为甘油18.53%、聚乙二醇-4008.54%、羟丙甲纤维素2.35%,单位面积累积透过量的二次多元回归模型:R1=-7 415.69+306.10A+167.47B+4 820.59C-8.26A2-9.81B2-1 025.75C2,累积透过率约为49.6%。结论通过星点设计-效应面法得到盐酸普萘洛尔凝胶处方基质优化模型,制备的盐酸普萘洛尔凝胶性质稳定、质量可控。

Objective To optimize the matrix formula of propranolol hydrochloride gels. Methods On the basis of single factor experiment, central composite design-response surface method was used to optimize the formula. Addition levels of glycerol （A）, PEG-400 （B） and HPMC （C） were evaluated as the independent variables.Eight-hour accumulative penetration amount per unit area measured by HPLC was used as the index. Quadratic polynomial was used to estimate the relationship between the index and the independent variables, and to delineate response surface and overlay contour plots in order to select the optimal formulations.Finally, predicted responses were verified. Results The optimized formula consisted of 18.53% glycerol, 8.54% PEG-400 and 2.35% HPMC.The quadratic polynomial regression model of 8-h accumulative penetration amount per unit area：R1=-7 415. 69＋306. 10A＋167. 47B＋4 820. 59C-8. 26A2-9. 81B2-1 025. 75C2 , and the cumulative transmittance was 49.6%. Conclusion A credible model is established by using central composite design-response surface method and the formula of propranolol hydrochloride gels is optimized and the gel is stable and controllable.