Box-Behnken Experimental Design in Development of Glimepiride Floating Matrix Tablets

Abstract

Floating matrix tablets of Glimepiride were developed to enhance its bioavailability by prolonging the gastric residence time in which Glimepiride was chosen as a model drug because of its has incomplete absorption due to its low gastric residence time. Floating matrix tablets were prepared using melt granulation technique. Bees wax was used as a hydrophobic meltable material. Hydroxypropylmethyl cellulose (Hypromellose K4MCR), sodium bicarbonate (sodium bicarb.) and ethyl cellulose (EC) were used as matrixing agent, gas generating agent and floating enhancer, respectively. Tablets were evaluated for physical characteristics such as weight, thickness, hardness, % friability and drug content. Tablets also were subjected to in vitro evaluation as buoyancy test (floating lag time), floating duration and drug release profile for 24 hours. A Box – Behnken design was applied to investigate the combined effect of 3 formulation variables including amount of hypromellose (X1), sodium bicarbonate (X2) as well as ethyl cellulose (X3). Fifteen batches were prepared and evaluated. Floating lag time, Flag (Y1), percent of drug released in 5 hours (Y2) and percent of drug released in 12 hours (Y3) were taken as responses. Obtained results of multiple regression analysis indicated that, high level of hypromellose (50 mg), high level of sodium bicarbonate (20 mg) and intermediate level of ethyl cellulose (15 mg) should be used to manufacture the tablet formulations with the desired in vitro floating time and dissolution. In addition; Formulations developed using Box – Behnken design, were fitted to various kinetic models for drug release. Formulation F7 was selected as a promising formulatio