APPLICATION OF CURDLAN TO CONTROLLED DRUG-DELIVERY .2. IN-VITRO AND IN-VIVO DRUG-RELEASE STUDIES OF THEOPHYLLINE-CONTAINING CURDLAN TABLETS

Tablets (300 mg) having two different surface areas were prepared from spray-dried particles of curdlan (100 mg)/theophylline(200 mg). Drug release from the tablets was studied in vitro and in vivo. The in vitr o drug release from a tablet with a larger surface area (Tab L) was fa ster than that with a smaller one (Tab S). The water uptake of Tab L w as larger than that of Tab S, probably due to the difference in the ta blets' surface areas. However, the water uptake was not a rate-determi ning step for the drug release from curdlan tablets containing a large amount of theophylline. A straight line was obtained when release % w as plotted vs. time. The slope of each curve was calculated as 0.59 fo r Tab L and 0.58 for Tab S. This indicates that the release mechanism is non-fickian diffusion controlled. In addition, the curdlan tablets or theophylline powder were administered orally to 5 healthy volunteer s, and saliva concentrations of theophylline were determined. Each sal iva concentration was converted to plasma concentration using the sali va to plasma ratio of the drug in each subject. The AUC of Tab L was n early the same as that of powder, while the AUC of Tab S was smaller t han that of powder. The mean residence times (MRTs) of theophylline po wder, Tab S and Tab L were 11.1+/-1.5, 25.4+/-6.3 and 17.1+/-1.5 h (N= 4-5, mean+/-S.D.), respectively. The mean dissolution times (MDTs) of Tab L in vivo and Tab S in vivo were 5.0+/-2.1 (N=5, mean+/-S.D.) and 13.9+/-5.4h (N=4, meam+/-S.D.), respectively. On the other hand, the M DTs of Tab L in vitro and Tab S in vitro were 4.8 and 11.2h, respectiv ely. In vivo drug release was very similar to in vitro drug release in both tablets. The lower bioavailability of Tab S suggested that the d rug release had not been completed during the gastrointestinal transit period. Tab L would thus be a better controlled release form than Tab S.