The Artificial Stomach and Duodenum (ASD): A physiologically relevant in vitro dissolution tool

The artificial stomach and duodenum (ASD) is a physiologically relevant in vitro dissolution tool that simulates the pH, mixing conditions, fluid composition and fluid flow in the gastric and duodenum compartments[1]. This tool is designed to generate gastric and duodenal concentration profiles to capture dissolution, precipitation and supersaturation phenomena under conditions that simulate the in vivo environment. Duodenal concentration profiles generated from ASD experiments have the potential to provide a rank order prediction of in vivo absorption of compounds as a function of formulation, gastric pH, or gastric emptying time. In this work, we report the IVIVC we established between ASD duodenal concentration profiles generated in our lab, and human in vivo duodenal concentration profiles that were obtained upon oral administration of solution doses of ketoconazole and dipyridamole to healthy volunteers[2]. As an example that demonstrates the application of this tool, we also report on the rank order IVIVC we established between the plasma exposure of dipyridamole[3] and ASD duodenal concentration profiles we generated, under standard and elevated gastric pH conditions. [1]Carino, S. et al. 2006; Relative bioavailability estimation of carbamazepine crystal forms using an artificial stomach-duodenum model. J. Pharm Sci 95(1), 116-125. [2] Psachoulias, D., et al. 2011; Precipitation in and Supersaturation of Contents of the Upper Small Intestine After Administration of Two Weak Bases to Fasted Adults. Pharm. Research, 28(12): 3145-3158 [3] Russell, T. L., et al. 1994; pH-Related Changes in the Absorption of Dipyridamole in the Elderly. Pharm. Research 11 (1): 136-143