Enhanced oral bioavailability of poorly absorbed drugs. I. Screening of absorption carrier for the ceftriaxone complex.

In this study, we attempted to improve the oral absorption of ceftriaxone (CTX) by using an absorption carrier and the CTX complex together. After the CTX-Ca-carrageenan gel complex was prepared, several kinds of compounds (Capmul MCM C10, Gelucire 44/14, glycyrrhizin) were screened as potential oral enhancers for our experiment and the intestinal morphologies in rats were examined. Of these compounds, the mono- and diglyceride mixtures, Capmul MCM C10 greatly enhanced the gastrointestinal absorption of CTX when this carrier was coadministered with the complex in rats. Percent bioavailability was attained in rats by the enteral route ranging from 55 to 79% when this complex was administered with various doses of Capmul MCM C10. Furthermore, the surface morphology of the complex has a highly smooth appearance as seen under scanning electron microscopy after preparation. No treatment-related signs of any damage were observed on the administrations intestinal membrane when morphologies were examined in rats after the complex and the absorption carrier were coadministered. The results of the observation suggest that Capmul MCM C10 is a promising carrier, having a good balance between bioavailability enhancing activity and safety, for the oral delivery of CTX when it is coadministered with complex. Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association