An Artificial Gut/Absorption Simulator: Description, Modeling, and Validation Using Caffeine.

The purpose of this study was to develop and validate a simultaneous dissolution and absorption testing tool, the "artificial gut simulator" (AGS), for oral drug formulations. The AGS was constructed using hollow fibers and housed in a 3-mL UV spectrophotometric cuvette that provided a large surface area-to-volume ratio to simulate absorption at a physiological rate. A quasi-steady-state model describing absorption was developed and validated using a high aqueous solubility, BCS-I model compound, caffeine. This model was used to optimize the AGS operating parameters to simulate physiological gastric emptying and caffeine absorption, which was further input into a one-compartment pharmacokinetic (PK) model. The in vivo caffeine plasma concentration-time profiles matched those predicted by the PK model with in vitro input from the AGS. This work provides a framework for establishing an in vitro/in vivo correlation with high-permeability, BCS-II supersaturating drug formulations, which will be explored in the future studies.