Optimization of Propranolol Hydrochloride Sustained-Release Pellets Using Box-Behnken Design and Desirability Function

Abstract

The objective of the present study was to evaluate three process parameters for the application of ethylcellulose films from organic solutions to obtain multiparticulate controlled drug delivery of propranolol hydrochloride. The coating process was developed in a classical coating pan.

A Box-Behnken central composite design was used to evaluate the effect of the film thickness (expressed as the amount of lacquer applied on pellets' surface unit), concentration of lacquer in the coating dispersion, and the plasticizer concentration on the independent variables. Those were t₈₅, the degree of sticking in the coating pan, and the duration of the coating process. Contour and response surface plots were depicted based on the equation given by the model. Because the results were competitive, i.e., improving one response had an opposite effect on another one, an overall desirability function was described to ameliorate the interpretation of the results. The optimization procedure generated the maximum overall desirability value. A formulation was prepared under the optimized conditions yielding response values which were close to the predicted values.

To understand the mechanism of drug release from the optimized pellets various models were used to fit the dissolution data. The Higuchi model appears to provide the best correlation.