- Nonirritant bioadhesive drug release systems based on starch–acrylic acid graft copolymers prepared by radiation of starch and acrylic acid mixtures with 60 Co were developed for buccal application. The release rate of theophylline (TPL), used as a model drug, depended on the ratio of starch to acrylic acid and on the presence of cations in the graft copolymers, but was practically not affected by the pH (between pH 3 and 7) of the dissolution medium nor by the type of starch used (corn, rice, or potato). Possible release mechanisms are discussed for specific conditions. In general, the release behavior of the graft copolymers was found to be non-Fickian, n value being between 0.6 and 0.96, suggesting that the release was controlled by a combination of tablet erosion and the diffusion of the drug from the swollen matrix. Incorporation of divalent cations into the graft copolymers led to a significant decrease in swelling erosion of the tablets as well as a substantial retardation of drug release. Highest work of adhesion was obtained with graft copolymers containing calcium ions as well as longer time of adhesion on dogs' gingiva.