AN ORGANIC ACID-INDUCED SIGMOIDAL RELEASE SYSTEM FOR ORAL CONTROLLED-RELEASE PREPARATIONS .2. PERMEABILITY ENHANCEMENT OF EUDRAGIT RS COATING LED BY THE PHYSICOCHEMICAL INTERACTIONS WITH ORGANIC-ACID
S. Narisawa et al., AN ORGANIC ACID-INDUCED SIGMOIDAL RELEASE SYSTEM FOR ORAL CONTROLLED-RELEASE PREPARATIONS .2. PERMEABILITY ENHANCEMENT OF EUDRAGIT RS COATING LED BY THE PHYSICOCHEMICAL INTERACTIONS WITH ORGANIC-ACID, Journal of pharmaceutical sciences, 85(2), 1996, pp. 184-188
The drug release mechanism of the sigmoidal release system (SRS), whic
h is a newly developed multiple-unit type time-controlled release syst
em, was investigated. The drug release rate from the Eudragit RS-coate
d theophylline beads was considerably enhanced in succinic acid aqueou
s solution compared with the release rate in water. However, the drug
release rate from the beads coated with Eudragit NE 30D, which has no
quaternary ammonium groups in the polymer chain, was not affected by s
uccinic acid, suggesting that the quaternary ammonium groups of Eudrag
it RS are essential to produce the unique drug release profile of the
SRS. ion-exchange experiments revealed that organic acids could intera
ct with Eudragit RS by an ion exchanging mode to various extents depen
ding on the acid species. To examine the individual effect of dissocia
ted and undissociated forms of succinic acid on the drug release behav
ior of the Eudragit RS-coated theophylline beads, dissolution studies
were performed in succinic acid or monosodium succinate aqueous soluti
ons with various concentrations. The drug release rate was found to ch
ange depending on the concentration of either the dissociated or, the
undissociated form of succinic acid with different concentration depen
dency. From the glass transition temperature measurement using Eudragi
t RS cast film, it was assumed that the undissociated succinic acid wa
s distributed to the hydrophobic segment of the polymer, resulting in
the increase in mechanical flexibility of the film; whereas the dissoc
iated succinic acid electrostatically interacted with the quaternary a
mmonium groups of the polymer to promote the distribution and to creat
e new ionic circumstances: both effects of the organic acid can accele
rate the hydration of Eudragit RS film. All these results suggest that
the unique S-shaped drug release profile of SRS can be brought about
by a drastic increase in the permeability through the hydration of Eud
ragit RS-based coating during the drug release process.