Importance of dissolution process on systemic availability of drugs delivered by colon delivery system

Abstract

The relationship between in vitro drug release characteristics from colon delivery systems and in vivo drug absorption was investigated using three kinds of delayed-release systems. 5-aminosalicylic acid (5-ASA), tegafur (FT) and carbamazepine (CBZ) were selected as model drugs. Pressure-controlled colon delivery capsules (PCC) for liquid preparations, time-controlled colon delivery capsules (TCC) for liquid and solid preparations and Eudragit S coated tablets for solid preparations were used in this study. At first, in vitro dissolution tests for all preparations were performed. Drug release from solid preparations was delayed compared to that from liquid preparations with all three drugs. Next, these preparations were administered to fasted beagle dogs. For 5-ASA, the mean C maxs (peak level) of Eudragit S coated tablets and PCC were 5.52 and 16.89 μg ml −1, respectively. The mean T maxs (time when drug reached peak level) were 3.0 and 5.3 h. AUCs were 22.57 and 48.09 μg·h ml −1, respectively. For FT, C maxs of Eudragit S coated tablet and PCC were 0.87 and 1.46 μg ml −1, and T maxs were 7.0 and 6.7 h, respectively. AUCs were 9.73 and 15.55 μg·h ml −1 and bioavailabilities were 43.79 and 70.84%. For CBZ, the mean C maxs of liquid preparations and solid preparations were 0.37 and 0.22 μg ml −1, respectively. The mean T maxs were 4.7 and 4.3 h. AUCs were 0.673 and 0.392 μg·h ml −1. With liquid preparations, drug was thought to contact to the colonic membrane easily because of lack of interference by stools, and to be absorbed well as compared with solid preparations. From these findings, drug release from colon delivery systems and drug dissolution in the colonic lumen are very important factors for the systemic availability of drugs from the colon delivery systems.