Application and Validation of an Advanced Gastrointestinal In Vitro Model for the Evaluation of Drug Product Performance in Pharmaceutical Development. Issue 11 (15th September 2014)

• Record Type: Journal Article
• Authors: Barker, Richard; Abrahamsson, Bertil; Kruusmägi, Martin
• Is Part Of: Journal of pharmaceutical sciences. Volume 103:Issue 11(2014:Nov.)
• Page Start: 3704
• Page End: 3712
• Publication Date: 2014-09-15
• Subjects: Pharmacy -- Periodicals; 615.1
• DOI: 10.1002/jps.24177
• Languages: English
• ISSNs: 0022-3549

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Methods to understand and predict the oral bioavailability of drug products are a prioritized research area within the pharmaceutical industry. Models to predict oral bioavailability have the potential to reduce risk, time, and cost in development as well as decrease the need for animal studies. The TNO intestinal model (TIM‐1) is an advanced dissolution model deployed by AstraZeneca since 2008. This article presents a systematic evaluation of TIM‐1 against <italic>in vivo</italic> data. The relative performance of compounds and formulations tested in TIM‐1 and <italic>in vivo</italic> was compared both by a qualitative analysis and a linear regression analysis of relative exposure measures between test and reference formulations in TIM‐1 and <italic>in vivo</italic>. The TIM‐1 correctly predicted <italic>in vivo</italic> rank order in 84% and 79% of cases for AUC and <italic>C</italic><sub>max</sub>, respectively, when using the 3‐h time point. There was only one case for <italic>C</italic><sub>max</sub> in which TIM‐1 did not predict an <italic>in vivo</italic> difference. The correlation coefficient (<italic>R</italic><sup>2</sup>) between relative (test vs. reference formulations) fraction available in TIM‐1 after 3 h and AUC was 0.78. Thus, this study suggests that the TIM‐1 system can be used to assess the risk for significant differences in exposure between formulations and compound modifications. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3704–3712, 2014</p> </abstract>