AN ORGANIC ACID-INDUCED SIGMOIDAL RELEASE SYSTEM FOR ORAL CONTROLLED-RELEASE PREPARATIONS .3. ELUCIDATION OF THE ANOMALOUS DRUG-RELEASE BEHAVIOR THROUGH OSMOTIC PUMPING MECHANISM
S. Narisawa et al., AN ORGANIC ACID-INDUCED SIGMOIDAL RELEASE SYSTEM FOR ORAL CONTROLLED-RELEASE PREPARATIONS .3. ELUCIDATION OF THE ANOMALOUS DRUG-RELEASE BEHAVIOR THROUGH OSMOTIC PUMPING MECHANISM, International journal of pharmaceutics, 148(1), 1997, pp. 85-91
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.