Effect of plasticizers on drug release from polymethracrylate and polyvinyl acetate matrices prepared by thermal granulation

Abstract

The effect of plasticizers on the release rate of theophylline matrices prepared by thermal granulation using ammonio methacrylate copolymer type B (Eudragit RS 100) and polyvinyl acetate/polyvinyl pyrrolidone (Kollidon SR) as matrix forming agent was investigated. The thermal granulation was conducted at the temperature of 60 ํC and 80 ํC. Various methods were employed to incorporate the plasticizers, triethyl citrate (TEC) and dibutyl phthalate (DBP) into the polymer. The glass transition temperature (Tg) of Eudragit RS and Kollidon SR before plasticization was 64.2 ํC and 40.1 ํC, respectively. The plasticization efficiency of TEC and DBP in reduction of Tg of both polymers were comparable. Co-spray drying of polymer with plasticizer was found to be the effective incorporation method to produce the plasticizer polymer powder prior to thermal granulation with the drug powder. For each percentage amount of TEC and DBP incorporated, Tg of Eudragit RS 100 decreased for 2.26 ํC and 2.6 ํC, respectively and Tg of Kollidon SR decreased for 1.55 ํC for each percentage of both plasticizer. Granulation process temperature slightly affected drug release rate of Kollidon SR system. An increase of granulation process temperature to 80 ํC significantly decreased in drug release rate of Eudragit RS system both with and without plasticizer. Compression force employed to prepare the matrices and pH of dissolution medium had no significant effect on drug release rate of these two systems