1 Pharmaceutical Design and Drug Delivery, Department of Pharmacy, Faculty of Health and Medical Sciences, Københavns Universitet2 IKVH Fysiologi og ernæring samt pelsdyrfarmen, Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, Københavns Universitet3 Institute of Pharmaceutical Technology, Goethe University, Frankfurt/Main, Germany.4 Department of Global Medicines Development, AstraZeneca R&D, S-431 83 Mölndal, Sweden.5 Drug Product Development, Pharmaceutical Development and Manufacturing Sciences, Janssen Research and Development, Johnson & Johnson, Beerse, Belgium.6 Drug Delivery and Disposition, KU Leuven, Leuven, Belgium.7 Product Development, GlaxoSmithKline R&D, Harlow, United Kingdom.8 Clinical Pharmacology and Pharmacometrics, AstraZeneca R&D, Alderley Park, Macclesfield SK10 4TG, United Kingdom.9 Biologics and Pharmaceutical Science, H.Lundbeck A/S, Ottiliavej 9, DK 2500 Valby, Denmark.10 Biopharmaceutics and Pharmaceutical Technology, University of Greifswald, Greifswald, Germany.11 Development Laboratories, MSD, Hoddesdon, United Kingdom.12 Drug Product Design, Pfizer PGRD, Sandwich, Kent CT13 9NJ, United Kingdom.13 TNO, Zeist, The Netherlands.14 Material Science and Early Characterization, Research Center Aprath, Bayer Pharma AG, Germany.15 Faculty of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis, 15771 Athens, Greece.16 Drug Delivery and Disposition, KU Leuven, Leuven, Belgium. Electronic address: email@example.com Pharmaceutical Design and Drug Delivery, Department of Pharmacy, Faculty of Health and Medical Sciences, Københavns Universitet
Accurate prediction of the in vivo biopharmaceutical performance of oral drug formulations is critical to efficient drug development. Traditionally, in vitro evaluation of oral drug formulations has focused on disintegration and dissolution testing for quality control (QC) purposes. The connection with in vivo biopharmaceutical performance has often been ignored. More recently, the switch to assessing drug products in a more biorelevant and mechanistic manner has advanced the understanding of drug formulation behavior. Notwithstanding this evolution, predicting the in vivo biopharmaceutical performance of formulations that rely on complex intraluminal processes (e.g. solubilization, supersaturation, precipitation…) remains extremely challenging. Concomitantly, the increasing demand for complex formulations to overcome low drug solubility or to control drug release rates urges the development of new in vitro tools. Development and optimizing innovative, predictive Oral Biopharmaceutical Tools is the main target of the OrBiTo project within the Innovative Medicines Initiative (IMI) framework. A combination of physico-chemical measurements, in vitro tests, in vivo methods, and physiology-based pharmacokinetic modeling is expected to create a unique knowledge platform, enabling the bottlenecks in drug development to be removed and the whole process of drug development to become more efficient. As part of the basis for the OrBiTo project, this review summarizes the current status of predictive in vitro assessment tools for formulation behavior. Both pharmacopoeia-listed apparatus and more advanced tools are discussed. Special attention is paid to major issues limiting the predictive power of traditional tools, including the simulation of dynamic changes in gastrointestinal conditions, the adequate reproduction of gastrointestinal motility, the simulation of supersaturation and precipitation, and the implementation of the solubility-permeability interplay. It is anticipated that the innovative in vitro biopharmaceutical tools arising from the OrBiTo project will lead to improved predictions for in vivo behavior of drug formulations in the GI tract.
European Journal of Pharmaceutical Sciences, 2014, Vol 57, p. 342-66