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

Abstract

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 Y 5 (cumulative percent drug released after 12 h) was Y5 = 89.83 - 11.98X1 + 2.82X2 - 4.31X12 + 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. © 2005 Elsevier B.V. All rights reserved.