PERORAL SUSTAINED-RELEASE FILM-COATED PELLETS AS A MEANS TO OVERCOME PHYSICOCHEMICAL AND BIOLOGICAL DRUG-RELATED PROBLEMS - II - BIOAVAILABILITY AND TOLERANCE ASSESSMENT IN DOGS

Sustained-release (SR) dosage forms consisting of pellets coated with different pH-sensitive film layers, previously optimized in vitro with regard to pH independence of their durg release characteristics, were evaluated in vivo after single administration to Beagle dogs. In vivo performances were compared to those of a nonoptimized SR matrix table t and a reference instant release (IR) capsule, in terms of the observ ed plasma pharmacokinetic profiles for the parent drug (ucb 11056) and its primary metabolite (ucb 26201), the bioavailability results, and the drug tolerance data. All SR dosage forms were seen to be effective in prolonging the relatively short biological half-life of the compou nd and in reducing the incidence of concentration-related side-effects , e.g., emesis, and of behavioral symptoms, e.g., restlessness, discom fort, and indisposition. The film-coated SR pellets offer a number of advantages over the monolithic SR matrix system in terms of a drug del ivery pattern less dependent on pH changes in the gastrointestinal (GI ) tract, a higher flexibility for adjusting and controlling the pharma cokinetic profiles, and a consequently more efficient approach for kee ping all concentration-related side-effects under control.