中心组合设计法优化吗替麦考酚酯片的处方工艺

Optimization of the Formulation of Mycophenolate Mofetil Tablets by Central Composite Design

目的:研制吗替麦考酚酯片并考察其体外溶出度。方法:采用中心组合设计法优化处方工艺,以微晶纤维素的用量和羧甲基淀粉钠的用量为考察因素,溶出度为评价指标,分别用线性模型和非线性模型描述溶出度和两个影响因素之间的数学关系,根据最佳数学模型描绘效应面,选择最佳处方,并进行预测分析。结果:溶出度与微晶纤维素的用量和羧甲基淀粉钠的用量的关系不能用线性方程描述,三次多项式是描述指标与因素之间关系的最佳模型,相关系数为0.991 6,具有较高的可信度。优选的最佳条件:微晶纤维素用量29.27 g,羧甲基淀粉钠的用量10.68g。最佳处方溶出度的理论预测值与实测值平均偏差为:-7.47%。结论:所建立的模型预测性良好,优化处方制备的片剂崩散迅速,溶出完全,工艺简单可行。

Objective： To prepare mycophenolate mofetil tablets and study their in vitro dissolution. Method： The formulation was optimized by central composite design. Independent variables were mierocrystallinecellulose （MCC） content and earboxymethyl starch sodium （CMS-Na） content,and dependent variable was dissolution. Linear or nonlinear mathematic models were used to estimate the relationship between independent and dependent variables. Response surfaces were delineated according to the best-fit mathematic mod- els to screen the optimum formulation. Prediction was carried out through comparing the observed and predicted values. Result： Dissolu- tion was not linear to MCC and CMS-Na contents. The relationship between dependent and independent variables was best fitted to three-order quadratic equation. Its regression coefficient was as high as 0. 991 6. Optimum formulation was proposed to contain MCC 29. 27 g and CMS-Na 10. 68 g. Bias between predicted and observed values of dissolution was -7.47%. Conclusion： It shows that the optimum mathematic models are highly predictive. Prepared tablets by the optimized formulations can disintegrate rapidly, dissolve completely, and the preparation process is also simple and feasible.