A Novel in Vitro and Numerical Analysis of Shear-Induced Drug Release from Extended-Release Tablets in the Fed Stomach

Abstract

To design an in vitro apparatus that could simulate the in vivo range of surface shear stresses relevant for the human stomach under fed conditions. Computer simulations were combined with in vitro experiments to quantify tablet erosion rate vs. surface shear stress. From two separate computer models, of tablets in the fed stomach and of tablets in vitro, we first estimated the intragastric range of surface stress and Reynolds number (Re), and then designed a dissolution apparatus and parameter space to replicate the in vivo conditions. The in vitro tablet erosion was determined by a new rotating beaker apparatus that provided predictable surface shear on tablets. Tablet mass erosion rates were measured for two different extended-release tablets at a range of in vivo relevant surface shear stresses obtained by varying viscosity of test media and rotation rate of the beaker. Mass erosion rate and surface shear were found to be highly correlated. Erosion rate increased with surface shear more rapidly at "low" stresses (<35 dyne/cm2) independent of tablet material. At higher surface stress, erosion was strongly material dependent. Shear force effects on drug release from matrix tablets relevant for fed state are for the first time possible to predict by in vitro dissolution testing.