An attempt was made to develop a gastroretentive drug delivery system of carbamazepine using HPMC, sodium bicarbonate, and EC as matrixing agent, gas-generating agent, and floating enhancer, respectively. A simplex lattice design was applied to investigate the combined effect of 3 formulation variables (ie, amount of HPMC (X1), EC (X2), and sodium bicarbonate (X3). Results of multiple regression analysis indicated that low levels ofX1 andX2 and a high level ofX3 should be used to manufacture the tablet formulation with desired in vitro floating time and dissolution. Formulation S3 was selected as a promising formulation and was found stable at 40°C temperature and 75% RH for 3 months.