Preparation and in vitro evaluation of verapamil HCl and ibuprofen containing carrageenan beads

In order to establish a method to predict oral absorption of drugs, which are absorbed by the oligopeptide transporter (PepT1), fraction absorbed (F) of cephalosporin antibiotics was predicted from in vitro uptake into rat intestinal brush border membrane vesicles (BBMV). Using in vitro uptake data, F values of cephalosporins in humans were predicted using the equation derived from the complete radial mixing (CRM) model, which was proposed by Amidon et al. (Amidon et al., J. Pharm. Sci. 69 (1980) 1369). In the present study, uptake into BBMV was measured at 25 and 4°C in the presence of an H⁺-gradient, and the uptake clearance (CL_uptake) was calculated. Clearance for the uptake mediated by PepT1 (ΔCL_uptake) was then calculated as CL_uptake at 25°C minus that at 4°C. When ΔCL_uptake and F values were analyzed according to the present equation, fairly good correlation between ΔCL_uptake and F was observed. It was further demonstrated that the present method may be able to quantitatively predict F values of cephalosporins by using several cephalosporins as standards.