Abstract
An application of zein, a water-insoluble corn protein, to sustained-release tablets was studied. It was found that the drug release from the tablets prepared from spray-dried particles of zein/theophylline/brilliant blue FCF (BB) was affected by drug amount in the tablets and pepsin in a release medium, but little by pH and pancreatin in the medium. The theophylline release was apparently zero-order in the release medium containing pepsin probably due to the erosion of the tablets by the enzyme. The zein tablets containing BB were pepsin-resistance and the drug release was retarded. The addition of BB in the release medium also showed the same effect. Salivary concentrations of theophylline following oral administration of the drug powder, the zein tablets and a commercially obtained sustained-release tablet were determined in 4 male healthy volunteers. The dose-normalized AUCs of these theophylline preparations did not differ significantly, suggesting that the extent of bioavailability of these preparations was much the same. The mean residence times (MRTs) of T41 tablet (pepsin-sensitive ; zein : theophylline=4 : 1) were not different from those of the commercial tablets significantly. However, the MRTs of T41B1 tablet (pepsin-resistant ; zein : theophylline : BB=4 : 1 : 0.1, 31.8±9.0h, mean±SD, n=4) was significantly longer than that of T41 (20.9±4.1h, mean±SD, n=4) (p<0.05, paired t-test). T41B1 tablets might be pepsin-resistance even in vivo.
