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 Department of Pharmacy, Uppsala University, Biomedical Centre P.O. Box 580, SE-751 23 Uppsala, Sweden.4 Biologics and Pharmaceutical Science, H. Lundbeck A/S, Ottiliavej 9, 2500, Valby, Denmark.5 Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.6 Novartis7 Pharmaceutical Development, AstraZeneca R&D, Mölndal, Sweden.8 Sirius Analytical Instruments Ltd., Riverside, Forest Row Business Park, Forest Row, East Sussex RH18 5DW, UK.9 ChemPharm Development, Johnson & Johnson Pharmaceutical Research & Development, 2340 Beerse, Belgium.10 Institute of Pharmaceutical Technology, Goethe Universität, 60438 Frankfurt/Main, Germany.11 Basic Pharmaceutical Sciences, Merck Research Laboratories, Merck & Co., Inc., USA.12 Strathclyde Institute for Pharmacy and Biomedical Sciences, Robertson Wing, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, Scotland, UK.13 Drug Product Design, Pfizer PGRD, Sandwich, Kent CT13 9NJ, UK.14 Material Science and Early Characterization, Bayer Pharma AG, Research Site Wuppertal-Aprath, Germany.15 Novartis16 Pharmaceutical Design and Drug Delivery, Department of Pharmacy, Faculty of Health and Medical Sciences, Københavns Universitet
current status and unmet needs
Preformulation measurements are used to estimate the fraction absorbed in vivo for orally administered compounds and thereby allow an early evaluation of the need for enabling formulations. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary of the pharmaceutical profiling methods available, with focus on in silico and in vitro models typically used to forecast active pharmaceutical ingredient's (APIs) in vivo performance after oral administration. An overview of the composition of human, animal and simulated gastrointestinal (GI) fluids is provided and state-of-the art methodologies to study API properties impacting on oral absorption are reviewed. Assays performed during early development, i.e. physicochemical characterization, dissolution profiles under physiological conditions, permeability assays and the impact of excipients on these properties are discussed in detail and future demands on pharmaceutical profiling are identified. It is expected that innovative computational and experimental methods that better describe molecular processes involved in vivo during dissolution and absorption of APIs will be developed in the OrBiTo. These methods will provide early insights into successful pathways (medicinal chemistry or formulation strategy) and are anticipated to increase the number of new APIs with good oral absorption being discovered.
European Journal of Pharmaceutical Sciences, 2014, Vol 57, p. 173-99