Central Composite Design for the Formulation and Optimization of Multi-unit Potential Colonic Drug Delivery of Budesonide for Ulcerative Colitis

摘要

The objective of this study was to develop a colon specific delivery system for budesonide to increase the efficacy in the treatment of ulcerative colitis using a statistical procedure. Pellets were prepared by powder layering of budesonide on nonpareils (0.5-0.6 mm) in a coating pan. Drug-layered pellets were coated with an inner layer of a combination of Eudragit® RL PO and RS PO and an outer layer of Eudragit FS in a fluidized-bed apparatus. Central composite design was used to study the effect of three independent variables. The independent variables selected were amount of Eudragit FS outer coating (X_1), proportion of Eudragit RL PO in the inner coating (X_2), amount of Eudragit RL PO-RS PO inner coating (X_3). Fifteen batches were prepared and evaluated for amount of drug released in 6 h (Y_1), amount of drug released in 12 h (Y_2). The proportion of the more hydrophilic polymer Eudragit RL PO had the most significant effect on drug release - higher proportion gave faster release; the amount of inner and outer coat did not have a significant effect on the rate of drug release at either 6 or 12 h in the range studied. The computer optimization process and contour plots predicted the levels of independent variables X_1, X_2, and X_3 (20.47, 44.48 and 2.71 % respectively) for colon targeting.