Integration of dissolution technology with computer simulations to predict oral drug absorption.

摘要

The objectives of this study were to develop dissolution test methods that can be used to predict the oral absorption of two drug products, etoricoxib (ArcoxiaRTM) and montelukast sodium (SingulairRTM), and to assess the capability of computer simulations using GastroPlus(TM) to establish in vitro/in vivo correlations (IVIVC).;Simulations indicated that montelukast sodium bioavailability is dissolution rate limited, while that of etoricoxib is neither permeability nor dissolution rate limited. Physiologically based computer simulation models using in vitro data are a promising tool in predicting the in vivo behaviour of oral drug products and for establishing IVIVC.;Drug solubility was measured in different media, and the dissolution behaviour of the drug products were studied in the USP Apparatus 2 using the USP buffers and biorelevant dissolution media (BDM) and in the flow-through cells following dynamic pH change protocols. Drug permeability was assessed in vitro using the Caco-2 and MDCK cell culture techniques.