Optimization of Sotalol Floating and Bioadhesive Extended Release Tablet Formulations

A novel extended release sotalol HC1 tablet formulation which possesses a unique combination of floatation and bioadhesion for prolonged residence in the stomach has been developed. Tablets were produced by direct compression. A two-factor factorial, central, composite Box-Wilson experimental design was employed to develop and optimize the tablet formulation containing 240 mg sotalol HC1. The ratio of two major bioadhesive agents, sodium carboxymethylcellulose (NaCMC) to hydroxypropylmethylcellulose (HPMC), and the ratio of two direct compressible diluents, ethylcellulose (EC) to crosspovidone, were used as formulation variables (independent variables) for optimizing tablets response parameters, such as dissolution bioadhesive capability, tablet density and required compression force for producing 6 Kg hardness tablets. The data were also analyzed by means of quadratic response surface model. Response surfaces were generated as a function of formulation variables. An optimum direct compression, bioadhesive and floating tablet formulation of sotalol HCl was achieved by considering the dissolution characteristic as primary objective and using required compression force, bioadhesive capability as constraints within the experimental region. The surface model was validated for accurate prediction of response characteristics.