S. Narisawa et al., AN ORGANIC ACID-INDUCED SIGMOIDAL RELEASE SYSTEM FOR ORAL CONTROLLED-RELEASE PREPARATIONS, Pharmaceutical research, 11(1), 1994, pp. 111-116
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.