THE INFLUENCE OF BUFFER SPECIES AND STRENGTH ON DILTIAZEM HCL RELEASEFROM BEADS COATED WITH THE AQUEOUS CATIONIC POLYMER DISPERSIONS, EUDRAGIT RS, RL 30D

Purpose. Eudragit RL and RS 30D are pseudolatexes frequently used in t he coating of solid dosage forms. They are based on cationic copolymer s stabilized with quaternary ammonium groups lacrylate-methylmethacryl ate-trimethylammonioethyl methacrylate chloride). A pH-independent dru g release is expected because of the quaternary nature of the cationic groups. The objective was to explain a distinct ''pH-dependent'' drug release in various buffer media with coated diltiazem beads. Methods. The diltiazem HCl release from and water uptake of Eudragit RS/RL-coa ted beads was determined in various buffers of different buffer specie s, pH or concentration. Results. The drug release in the different buf fer media was in the following order: pH 5.0 acetate > pH 3.5 formate > pH 7.4 phosphate buffer > 0.1M HCl). This ''pH-dependent'' drug rele ase could be explained with an anion exchange process; the chloride co unterions of the quaternary groups were exchanged with the anionic buf fer species during the dissolution study. The water uptake of the coat ed beads correlated well with the drug release from the beads. Increas ing the buffer strength (acetate buffer) first increased and then decr eased the drug release, while increasing the ionic strength of differe nt buffers with NaCl decreased the drug release and eliminated the obs erved buffer effects because of the excess of chloride ions. Conclusio ns. The anionic buffer species and not the pH had a significant effect on the hydration and hence on the drug release from beads coated with the cationic polymers, Eudragit RS and RL.