Exploring clinically relevant dissolution specifications for oral solid dosage forms of weak acid drugs using an in silico modeling and simulation approach

Abstract

The aim of this study was to explore clinically relevant dissolution specifications for weak acid drugs using an in silico drug absorption model. Loxoprofen sodium and ibuprofen were used as model drugs in this study. An in silico drug absorption model was developed using Stella Professional software and the prediction model accurately represented the plasma concentration profiles of the model drugs following oral administration. Theoretical pharmacokinetic profiles and parameters of the model drugs were predicted using various dissolution rate values in gastrointestinal fluid. This in silico modeling and simulation approach suggests that it is possible to estimate the minimum required dissolution rate for bioequivalence, an example of a clinically relevant dissolution specification. Furthermore, an in vitro dissolution test was conducted for selected drug products of each model drug using paddle apparatus and the results were compared with the clinically relevant dissolution specifications predicted using the in silico simulation.