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

AbstractThe 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 ab sorption 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) m odel. Thein vivo caffeine plasma concentration-time profiles matched those predicted by the PK model within vitro input from the AGS. This work provides a framework for establishing anin vitro/in vivo correlation with high-permeability, BCS-II supersaturating drug formulations, which will be explored in the future studies.Graphical Abstract
Source: The AAPS Journal - Category: Drugs & Pharmacology Source Type: research