效应面法优化吲哚美辛HPMC／果胶／氯化钙骨架片的双相释放

考察HPMC／果胶／氯化钙骨架片中两个自变量果胶／氯化钙重量比和骨架总重量对吲哚美辛释放的影响。采用二因素五水平星点设计，效应面法优化Peppas方程拟合参数n、K和T0.1（10％释放时间）。自变量对双相释放参数n和K值有显著影响，n、K和T0.1值可用二次多项式拟合，线性拟合效果不佳。数学模型拟合和效应面结果表明果胶／氯化钙重量比和骨架总重量两个因素间有显著交互作用。在具有较大n和T0.1值和较小K值的优化处方中，其果胶／氯化钙的比例约为1．0，骨架总重量处于中间值，约200mg。优化处方只有很好的预测性，n、K和T0.1值的预测偏差介于-7．33％和6．26％之间。星点设计可用于优化和预测药物从HPMC／果胶／氯化钙骨架片的释放。

Optimization of the biphasic release of indomethacin from HPMC/pectin/calcium chloride matrix tablet by response surface methodology

We studied the effect of two independent variables,the pectin/calcium chloride weight ratio and the overall matrix weight in HPMC/pectin/calcium matrix tablet,on the release of indomethacin.A two-factor 5-level central composite experimental design was employed.Responses of the Peppas correlation parameters n and K and the 10% release time (T_(0.1)) were optimized by response surface methodology.Significant effect of the independent variables on the biphasic release parameters,n and K,was observed.N,K and T_(0.1) were well fitted with the second-order quadratic equations rather than linear equations.Moreover,the mathematic fitting and the response surfaces showed significant cross-interaction between the pectin/calcium chloride ratio and the overall matrix weight.The optimal formulation with larger n,longer T_(0.1) and smaller K consisted of medium pectin/calcium chloride ratio around 1.0 and medium matrix weight around 200 mg.Validation studies on the optimal formulations showed good predictability of the n,K and T_(0.1) values with biases within the range of-7.33% and 6.26%.Our results support that central composite design can be used to optimize drug release from HPMC/pectin/calcium matrix tablet with high predictability.