PERORAL SUSTAINED-RELEASE FILM-COATED PELLETS AS A MEANS TO OVERCOME PHYSICOCHEMICAL AND BIOLOGICAL DRUG-RELATED PROBLEMS - I - IN-VITRO DEVELOPMENT AND EVALUATION

In vitro preformulation testing has shown that the solubility and diss olution rate of the model drug compound ucb 11056 are highly pH depend ent. Considering this, different sustained-release (SR) oral dosage fo rms of ucb 11056 were developed aiming to obtain the most constant and complete release of the drug during transit in the gastrointestinal ( GI) tract. Classical approaches based on the use of SR formulations su ch as hydrophilic matrix tablets or pellets coated with one film-formi ng polymer (Eudragit(R) NE30D or L30D-55) did not fulfill all expectat ions on the basis of their in vitro evaluation, i.e., the drug release and pattern remained highly dependent on the pH of the dissolution me dium. Therefore, taking advantage of the flexibility of release adjust ment obtainable from coating of pellets with different kinds of pH-sen sitive film layers, a quite satisfactory pH independence of the releas e characteristics was obtained using formulation blends of neutral and anionic acrylic polymers. For the selected SR pellets batch 15 coated with NE30D/L30D-55 (7:3), the tridimensional topographic representati on of the drug release versus time and pH showed that, notwithstanding the pH-dependent aqueous solubility of the drug, the release profiles were relatively homogeneous for any pH value ranging between 1 and 7.