Application of Fibroin in Controlled Release Tablets Containing Theophylline

Abstract

The application of fibroin, a major silk protein, to controlled release type dosage tablets was investigated in vitro and in vivo. Fibroin tablets containing theophylline were easily prepared by a direct compression method without additives. Five types of fibroin tablets with the same surface area and different amounts of theophylline were prepared. In an in vitro drug study, the drug release from the tablets was not affected by the pH of the release medium. The greater the fibroin content in the tablets, the lower the percentage released at time t. The Higuchi plots of the release data showed a linear release profile, indicating that the drug release from the fibroin tablets was diffusion-controlled through the matrix. Theophylline powder or a TF-41 tablet (theophylline : fibroin=4 : 1), or a commercial tablet, Uniphyl (once-a-day type) was administered to 5 healthy volunteers. The areas under the saliva theophylline concentration-time curve (AUC) of Uniphyl and TF-41 to that of powder were 85% and 70%, respectively (fasted). Conversely, the mean residence time and mean absorption time of TF-41 were long compared to Uniphyl (fasted). Therefore, the reduction of bioavailability in TF-41 was due to the delayed release from the tablets in vivo. Taken after a meal, the AUCs of TF-41 and Uniphyl increased and the absorption was completed. This suggested that the drug release from TF-41 may increase due to the stimulation of food on TF-41 itself and due to movement of the gastro-intestinal tract. In conclusion, fibroin could be used as the matrix in controlled-release tablets.