Abstract
The aim of this work was to statistically optimize a novel high-dose, mesalazine colonic delivery matrix system, potentially suitable for once daily administration, using simple wet granulation method. A hydrophobic–hydrophilic polymeric blend was used to manipulate drug release. A three-factor, three-level Box–Behnken design was used to construct polynomial models correlating the dependent and independent variables. Independent formulation variables were the percentages of the hydrophilic polymer Carbopol® 940, hydrophobic polymer Eudragit® RS, and the superdisintegrant croscarmellose sodium. The cumulative percentages of drug released at 6, 10, and 14 h were selected as dependent variables and restricted to 7.5–22.5% (
Y
1
), 42.5–57.5 % (
Y
2
), and 72.5–87.5% (
Y
3
), respectively. A second-order polynomial equation fitted to the data was used to optimize the independent formulation variables. Based on Box–Behnken experimental design, different mesalazine release profiles were obtained. The optimized formulation containing 5.72% Carbopol®, 9.77% Eudragit® RS, and 1.45% croscarmellose sodium was prepared according to the software determined levels. It provided a release profile which was very close to the targeted release profile, where the calculated values of
f
1
and
f
2
were 8.47 and 67.70, respectively, and followed zero-order release kinetics.