Optimization and characterization of controlled release multi-particulate beads coated with starch acetate

The objectives of the present study were (1) to model the effects of process and formulation variables on in vitro release profile of a model drug dyphylline from multi-particulate beads coated with starch acetate (SA); (2) to validate the models using R2 and lack of fit values; (3) to optimize the formulation by response surface methodology (RSM); (4) to characterize the optimized product by thermal, X-ray and infrared spectroscopic analyses. Dyphylline loaded inert beads were coated using organic solution of SA with high degree of substitution. A three-factor, three-level Box-Behnken design was used for the optimization procedure with coating weight gain (X1), plasticizer concentration (X2) and curing temperature (X3) as the independent variables. The regression equation generated for Y5 (cumulative percent drug released after 12 h) was Y5 = 89.83-11.98X1 + 2.82X2 - 4.31X1(2) + 1.90X1X2. Optimization was done by maximizing drug release in 12 h and placing constraints at dissolution time points of 0.5, 1, 4 and 8 h. The drug release data of the optimized product were close to that predicted by the model. The models could explain 99% of variability in responses. Thermal, X-ray and infrared analyses suggested absence of any significant interaction of the drug with the excipients used in the formulation. SEM photographs showed the integrity of the coating layer.