Abstract:Objective: Prepare Etofibrate sustained release capsule;To optimize the formulation of Etofibrate sustained release capsule by Central Composite Design-Response Surface Method Ology(CCD-RSM). Methods: Etofibrate pellets were prepared by centrifugal granulation equipment,then they were coated by solution of PEG4000 and Etofibrate dissolute in Acetone. Aqueous dispersion of Acrylic Resins(Eudragit RL30D)was used for the sustained release layer coating. In the formulation design using CCD-RSM,independent variables were the mass ratio of solubilize layer,the mass ratio of PEG4000 in the solubilize layer,and the weight gain percentage of sustained release layer. The percentage of in vitro cumulative releases at 4 h,8 h and 24 h were dependent variables. Multilinear and quadratic models were used to estimate the relationship between the dependent and the independent variables,and to delineate RSM and overlay contour plots in order to select the optimal formulation. Results: The optimized formulation parameter was: weight ratio of solubilize layer was between 0.7-1.2;the mass ratio of PEG4000 in the solubilize layer was between 3.5%-12.8%;the weight gain percentage of sustained release layer was between 8.0%-13.5 %. Quadratic model showed better prediction capability than multilinear model. The quantitative relationships between three factors and three evaluation indexes were characterized. Moreover,in vitro release test of the selected optimal formulation indicated thigh approximation between the observed and estimated values. Conclusion: The CCD-RSM can be applied to optimize the formulation of Etofibrate sustained release capsule and the established model is of satisfactory predictive value.
[1] Roberto V. Process for preparing etofibrate or similar compounds containing sustained release microgranules and products thus obtained:US 957746[P].1990-09-18. [2]杨硕晔,郭允,陈西敬.制剂新技术在水难溶性药物中的应用研究进展[J].中国药房,2011,22(13):1228- 1231. [3]白靖,李骞,王静,等.药用丙烯酸树脂在制剂中的应用进展[J].中国药房,2011,22(17):1614-1617. [4] Johnson K, Hoppe HJ, Schatton W.Relative bioavailability of etofibrate.A comparison of an acute and a new sustained release formulation[J].Arzneimittelforschung, 1984,34(12):1785-1787.