Recent Advances in Dissolution Testing and Their Use to Improve In Vitro–In Vivo Correlations in Oral Drug Formulations

Abstract

Bioavailability of oral drug formulations is strongly dependent on the composition of the gastric and intestinal fluids and hydrodynamic conditions in the gastrointestinal tract. These affect the dissolution behavior of oral formulations and their subsequent absorption to the bloodstream. A detailed characterization of all these factors is almost impossible in an in vivo setting, which necessitates the use of in vitro experiments. However, the drug release/drug solubility information in the media representing the gastrointestinal tract obtained in an in vitro study is typically not directly determined in an in vivo experiment. Instead, it is more convenient to determine in vivo the drug concentration in plasma. In vitro–in vivo correlation (IVIVC) typically refers to mathematical relationships between in vitro dissolution behavior and in vivo drug concentration in plasma. IVIVC may be improved by approaches that better mimic in vivo conditions in an in vitro setting. These include mimicking of drug absorption and the composition and hydrodynamics of the release medium. Artificial gastrointestinal (GI) systems are designed to meet this objective. In this review, we discuss our current understanding of the IVIVC and the experimental approaches to improve the IVIVC. Some ex vivo approaches also fall within the scope of this review.