Optimization of divalproex sodium sustained-release tablets formulation by Plackett-Burman design and central composite design-response surface methodology

Objective To obtain the optimal formulation of divalproex sodium sustained-release tablets by Plackett-Burman design and central composite design-response surface methodology.Methods With similarity factor method as an index,significant influence fac-tors of divalproex sodium sustained-release tablets were screened by Plackett-Burman design.The amount of HPMC K100M, HPMC K15M and ethanol concentration were chosen as dependent variables and overall desirability method was chosen as independent varia-ble.Central composite design-response surface methodology was used to optimize the formulation by establishing multiple linear regres-sion and second-order quadratic models;deviation was carried out through comparing the observed and predicted values.Results It showed that the coefficient of correlation of second-order quadratic model was high.The related coefficient reached 0.9620.In this ex-periment,the established model could describe the good relation between factors and indexes and the outcome of prediction was good. Optimal formulation of divalproex sodium sustained-release tablets was as follows:HPMC K100M 286.72 mg,HPMC K15M 16.96 mg, ethanol concentration 27%.Conclusion The method of optimized sustained-release formulation is simple with good predictability, which is worthy of application and promotion.