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 release profile of sigmoidal release system (SRS), which is a newly developed multiparticulate oral time-controlled drug delivery system, the release mechanism was investigated. The dissolution studies were conducted for the theophylline-loaded SRS in water or in glucose aqueous solutions with different concentrations to vary osmotic pressure. In water, the initial lag time was extended with increasing coating level, whereas less change was observed in the subsequent drug release rate. On the other hand, drug release behaviors in aqueous glucose solutions extensively changed depending on the glucose concentrations; extending the lag time and decreasing the drug release rate. All the results obtained in the present study indicated that the anomalous theophylline release 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 rapid release. (C) 1997 Elsevier Science B.V.