Optimization of methacrylic acid ester copolymers blends as controlled release coatings using response surface methodology

The aim of this study was to statistically optimize the use of blends of methacrylic acid ester copolymers with different permeability properties as controlled-release coating systems for tablets to produce predictable predesigned release profiles. A full factorial design was used to study and optimize the use of methacrylic acid ester copolymers Eudragit(R) RS 30D and Eudragit(R) RL 30D as coating materials for controlled release. Directly compressed theophylline tablets were coated with aqueous dispersions containing different proportions of the two copolymers using a side-vented coating pan (Accela Cota(R)). The effect of polymer loading level at 5, 7.5, and 10% weight gain and curing time at 50degreesC for 12 and 24 hours were also evaluated. Coated tablets were tested for their drug release in water using a United States Pharmacopeia (USP) dissolution apparatus #2. The results showed that increasing the content of the lower permeability copolymer Eudragit(R) RS 30D, increasing the polymer load, and increasing curing time at 50degreesC resulted in slower drug release. A statistical model that describes and predicts the drug release properties of the coated tablets as a function of the copolymers ratio in the coating dispersion, polymer load, and curing time at 50degreesC was developed. The most significant factor affecting drug release was found to be the ratio of the two copolymers in the coating dispersion followed by the curing time at 50degreesC and the polymer loading level. Good correlations were observed between the model fitted values and the experimental values. An optimized formula prepared by superimposing two-dimensional contour plots was prepared; its release profile was found to be in agreement with the prediction obtained from the model.