The drug release mechanism of the sigmoidal release system (SRS), which is a newly developed multiple-unit type time-controlled release system, was investigated. The drug release rate from the Eudragit RS-coated theophylline beads was considerably enhanced in succinic acid aqueous 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 succinic acid, suggesting that the quaternary ammonium groups of Eudragit RS are essential to produce the unique drug release profile of the SRS. Ion-exchange experiments revealed that organic acids could interact with Eudragit RS by an ion exchanging mode to various extents depending on the acid species. To examine the individual effect of dissociated and undissociated forms of succinic acid on the drug release behavior of the Eudragit RS-coated theophylline beads, dissolution studies were performed in succinic acid or monosodium succinate aqueous solutions with various concentrations. The drug release rate was found to change depending on the concentration of either the dissociated or the undissociated form of succinic acid with different concentration dependency. From the glass transition temperature measurement using Eudragit RS cast film, it was assumed that the undissociated succinic acid was distributed to the hydrophobic segment of the polymer, resulting in the increase in mechanical flexibility of the film; whereas the dissociated succinic acid electrostatically interacted with the quaternary ammonium groups of the polymer to promote the distribution and to create new ionic circumstances: both effects of the organic acid can accelerate 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 Eudragit RS-based coating during the drug release process.

To achieve time-controlled or site-specific drug delivery in the gastrointestinal tract, a sigmoidal release system (SRS) was developed, which achieved a prolonged lag time, followed by rapid release. The theophylline beads with a thick Eudragit RS film coating showed very low drug release in water, whereas the release rate increased considerably in organic acid solutions. A hydration study of Eudragit RS films suggested that the increase in drug release was attributable to structural changes of the film induced by polymer-acid interactions. When succinic acid was incorporated into the core of Eudragit RS-coated theophylline beads, the drug release profile showed a typical sigmoidal pattern. SRS beads containing acetaminophen were also prepared by the same technique. Again, a sigmoidal release pattern was observed in which the lag time was prolonged with an increase in the coating level, whereas the drug release rate thereafter was almost constant irrespective of the coating level. Acetaminophen-containing SRS beads with different coating thickness were orally administered to beagle dogs. The drug plasma concentration curves showed lag periods similar to the in vitro lag time.

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In the vitrification of high-level radioactive liquid waste (HLW), the separation of sodium-molybdate melts is a problem because it reduces the chemical durability of the vitrified waste. A glass with both high MoO3 solubility and chemical durability is required for the safe disposal of radioactive waste. In this study, we investigate the effects of vanadium oxide on the phase separation of the molybdenum-rich phase and the water resistance of the resulting glass by phase equilibrium experiments and chemical durability test. Phase equilibrium experiments were performed on SiO2-B2O3-Al2O3-ZnO-CaO-Na2O-LiO2-MoO3 system glasses and on glasses with V2O5 added. The results showed that MoO3 solubility increased when V2O5 was added. The increase in MoO3 solubility in borosilicate melts may be associated with the viscosity-lowering effect of V2O5. Chemical durability tests were performed on borosilicate glass compositions obtained from phase equilibrium experiments. The normalized leaching rates of V2O5-bearing glasses were higher than those of other glasses. This is due to the higher network modifier/network former ratio of the glass tested. The normalized elemental mass loss of glass containing waste components increases with increasing leaching duration. This suggests that the waste component prevents the formation of a gel layer at the reaction front.