AN ORGANIC ACID-INDUCED SIGMOIDAL RELEASE SYSTEM FOR ORAL CONTROLLED-RELEASE PREPARATIONS .3. ELUCIDATION OF THE ANOMALOUS DRUG-RELEASE BEHAVIOR THROUGH OSMOTIC PUMPING MECHANISM

To provide a reasonable explanation for the unique S-shaped drug relea se profile of sigmoidal release system (SRS), which is a newly develop ed multiparticulate oral time-controlled drug delivery system, the rel ease mechanism was investigated. The dissolution studies were conducte d for the theophylline-loaded SRS in water or in glucose aqueous solut ions with different concentrations to vary osmotic pressure. In water, the initial lag time was extended with increasing coating level, wher eas less change was observed in the subsequent drug release rate. On t he other hand, drug release behaviors in aqueous glucose solutions ext ensively changed depending on the glucose concentrations; extending th e lag time and decreasing the drug release rate. All the results obtai ned in the present study indicated that the anomalous theophylline rel ease from the device was brought about by two mechanisms:; duration of the initial osmotic water-influx to the system to produce a lag time and the subsequent osmotic pumping process to provide a steady-state r apid release. (C) 1997 Elsevier Science B.V.