Journal of Pharmaceutical Sciences 2014-11-01

Evaluation of a three compartment in vitro gastrointestinal simulator dissolution apparatus to predict in vivo dissolution.

Susumu Takeuchi, Yasuhiro Tsume, Gregory E Amidon, Gordon L Amidon

Index: J. Pharm. Sci. 103(11) , 3416-22, (2014)

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Abstract

In vitro dissolution tests are performed for new formulations to evaluate in vivo performance, which is affected by the change of gastrointestinal (GI) physiology, in the GI tract. Thus, those environmental changes should be introduced to an in vitro dissolution test. Many studies have successfully shown the improvement of in vitro-in vivo correlations (IVIVC) by introducing those physiological changes into dissolution tests. The gastrointestinal simulator (GIS), a multicompartment in vitro dissolution apparatus, was developed to evaluate in vivo drug dissolution. A gastric-emptying rate along with transit rate are key factors to evaluate in vivo drug dissolution and, hence, drug absorption. Dissolution tests with the GIS were performed with Biopharmaceutical Classification System class I drugs at five different gastric-emptying rates in the fasted state. Computational models were used to determine in vivo gastric-emptying time for propranolol and metoprolol based on the GIS dissolution results. Those were compared with published clinical data to determine the gastric half-emptying time. In conclusion, the GIS is a practical tool to assess dissolution properties and can improve IVIVC.© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.