Once daily, high-dose mesalazine controlled-release tablet for colonic delivery: optimization of formulation variables using Box-Behnken design.
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.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Egypt.
Ahmed Abd
AA
Elbary
Ahmed A
AA
Aboelwafa
Ibrahim M
IM
Al Sharabi
D000180:Acrylic Resins / Q000737:chemistry; D000284:Administration, Oral; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry*; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003106:Colon; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D004339:Drug Compounding; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D019804:Mesalamine / Q000008:administration & dosage / Q000737:chemistry*; D008956:Models, Chemical; D015233:Models, Statistical; D011108:Polymers / Q000737:chemistry*; D012044:Regression Analysis; D015203:Reproducibility of Results; D012995:Solubility; D013608:Tablets, Enteric-Coated; D013678:Technology, Pharmaceutical / Q000379:methods*
D000180:Acrylic Resins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D005079:Excipients; D011108:Polymers; D013608:Tablets, Enteric-Coated; C050528:Eudragit RS; D019804:Mesalamine; C006903:carbopol 940; D002266:Carboxymethylcellulose Sodium