Technology to obtain sustained release characteristics of drugs after delivered to the colon

To determine the necessary technology by which sustained drug release is ob tained after drug is delivered to the colon, two kinds of microcapsules wer e prepared and were filled in a pressure-controlled colon delivery capsule (PCDC). As a model drug 5-aminosalicylic acid (5-ASA) was used, because the target site of 5-ASA is the entire large intestine. 5-ASA was microencapsu lated using a water-insoluble polymer, ethylcellulose (EC) or with pH-sensi tive polymers, Eudragit(TM) L-100 or S-100 and encased in PCDC. The particl e size of these microcapsules was around 800 mu m and the loading efficienc ies of 5-ASA were approximately 90%. In vitro dissolution tests were perfor med with the prepared microcapsules. The release rate of 5-ASA from the mic rocapsules was significantly prolonged as compared to 5-ASA powder, althoug h there were no significant differences in the release rates between these microcapsules. By incorporating the 5-ASA microcapsules into PCDC, sustaine d release PCDCs for colon delivery were prepared and in vivo evaluation was performed using beagle dogs. As a fast release colon delivery system, PCDC s were prepared with 5-ASA powder suspended in suppository base. After oral administration of the test preparations to beagle dogs, plasma 5-ASA conce ntrations were measured and sustained release characteristics of 5-ASA from the test preparations were evaluated from the plasma 5-ASA concentration-t ime profiles. The first appearance time of 5-ASA into the systemic circulat ion after oral administration were 3h for all the colon delivery preparatio ns and it was thought that these test preparations were delivered to the co lon. Both EC microcapsules and Eudragit S-100/RS-100 microcapsules in PCDC showed longer the mean residence time MRT, 8.2 +/- 0.6 h and 8.7 +/- 0.9 h, than Eudragit L-100/RS-100 microcapsules in PCDC where the MRT was 6.6 +/- 0.2 h. Since PCDCs containing 5-ASA powder exhibited a MRT of 7.0 +/- 1.0 h, these two types of preparations have suggested sustained release charact eristics.