AN ORGANIC ACID-INDUCED SIGMOIDAL RELEASE SYSTEM FOR ORAL CONTROLLED-RELEASE PREPARATIONS

To achieve time-controlled or site-specific drug delivery in the gastr ointestinal tract, a sigmoidal release system (SRS) was developed, whi ch achieved a prolonged lag time, followed by rapid release. The theop hylline beads with a thick Eudragit RS film coating showed very low dr ug release in water, whereas the release rate increased considerably i n organic acid solutions. A hydration study of Eudragit RS films sugge sted that the increase in drug release was attributable to structural changes of the film induced by polymer-acid interactions. When succini c acid was incorporated into the core of Eudragit RS-coated theophylli ne beads, the drug release profile showed a typical sigmoidal pattern. SRS beads containing acetaminophen were also prepared by the same tec hnique. Again, a sigmoidal release pattern was observed in which the l ag time was prolonged with an increase in the coating level, whereas t he drug release rate thereafter was almost constant irrespective of th e coating level. Acetaminophen-containing SRS beads with different coa ting thickness were orally administered to beagle dogs. The drug plasm a concentration curves showed lag periods similar to the in vitro lag time.