The purpose of this study was to evaluate the usefulness of the in vitro biorelevant gastrointestinal transfer (BioGIT) system in assessing the impact of dose and formulation on early exposure by comparing in vitro data with previously collected human plasma data of low solubility active pharmaceutical ingredients. Eight model active pharmaceutical ingredients were tested; Lu 35-138C (salt of weak base in a HP-beta-CD solution, three doses), fenofibrate (solid dispersion, tablet, two doses), AZD2207 EQ (salt of weak base, capsule, three doses), posaconazole (Noxafil® suspension, two doses), SB705498 (weak base, tablets vs. capsules), cyclosporine A (Sandimmun® vs. Sandimmun® Neoral), nifedipine (Adalat® capsule vs. Macorel® tablet), and itraconazole (Sporanox® capsule vs. Sporanox® solution). AUC values were calculated from the apparent concentration versus time data in the duodenal compartment of the BioGIT system. Differences in AUC values were evaluated versus differences in AUC and in AUC values calculated from previously collected plasma data in healthy adults. Ratios of mean AUC, mean AUC, and mean AUC values were estimated using the lowest dose or the formulation with the lower AUC value as denominator. The BioGIT system qualitatively identified the impact of dose and of formulation on early exposure in all cases. Log-transformed mean BioGIT AUC ratios correlated significantly with log-transformed mean plasma AUC ratios. Based on this correlation, BioGIT AUC ratios between 0.3 and 10 directly reflect corresponding plasma AUC ratios. BioGIT system is a valuable tool for the assessment of the impact of dose and formulation on early exposure to low solubility drugs.

No abstract