Central composite design for the formulation and optimization of a multi-unit potential colonic drug delivery system of budesonide for ulcerative colitis.

Budesonide is a potent glucocorticoid with high affinity for the glucocorticoid receptor, which is used for the treatment of inflammatory bowel diseases. Current oral formulations of budesonide present low efficacy against ulcerative colitis because of the premature drug release in the upper part of the gastrointestinal tract. 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 (X1), proportion of Eudragit RL PO in the inner coating (X2), amount of Eudragit RL PO-RS PO inner coating (X3). Fifteen batches were prepared and evaluated for amount of drug released in 6 h (Y1), amount of drug released in 12h (Y2). 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 X1, X2, and X3 (0.79, 0.69 and 0.35 respectively), for colon targeting.

Box-Behnken experimental design in the development of pectin-compritol ATO 888 compression coated colon targeted drug delivery of mesalamine.

The aim of this study was to investigate the combined influence of 3 independent variables in the compression coated tablet of mesalamine for ulcerative colitis. A 3-factor, 3-level Box-Behnken design was used to derive a second order polynomial equation and construct contour plots to predict responses. The independent variables selected were: percentage of polymers (pectin and compritol ATO 888) in compression coating (X(1)), coating mass (X(2)) and coating force (X(3)). Fifteen batches were prepared and evaluated for percent of drug released in 5 h (Y(5)), time required for 50 % mesalamine to dissolve (t(50)) with rat cecal (RC) content and without rat cecal content (t(50)), percent of drug released in 24 h in the presence of rat cecal content (Y(24) with RC). Transformed values of independent and dependent variables were subjected to multiple regressions to establish a full-model second-order polynomial equation. F was calculated to confirm the omission of insignificant terms from the full-model equation. The computer optimization process and contour plots predicted the levels of independent variables X(1), X(2), and X(3) (0, 0.2 and -0.15, respectively) for colon targeting and total percent of drug released up to 24 h.