Advantage of the Dissolution/Permeation System for Estimating Oral Absorption of Drug Candidates in the Drug Discovery Stage

In order to increase the success rate in the development of oral drugs, an in vitro method, which can accurately estimate human oral absorption of a large variety of compounds from solid formulations, is required in the drug discovery stage. A dissolution/permeation (D/P) system is an in vitro system that simultaneously evaluates dissolution and permeation processes of drugs administered orally. In this study, we have investigated the advantages of a D/P system for use in the provisional estimation of human oral absorption of a drug (absorbed fraction, Fa) by applying it in its solid state. The D/P system mounted with a Madin-Darby canine kidney (MDCK) II cell monolayer was used to simultaneously evaluate the dissolved and the permeated amounts (% of dose) of 48 marketed drugs. Slightly modified, fasted-state simulated intestinal fluid (FaSSIFmod, 8 mL) was used as the apical medium of the D/P system. Each test drug was applied to the apical side of the D/P system as a suspension at one-hundredth of the c...