TY - JOUR
T1 - Early pharmaceutical profiling to predict oral drug absorption
T2 - current status and unmet needs
AU - Bergström, Christel A S
AU - Holm, René
AU - Jørgensen, Søren Astrup
AU - Andersson, Sara B E
AU - Artursson, Per
AU - Beato, Stefania
AU - Borde, Anders
AU - Box, Karl
AU - Brewster, Marcus
AU - Dressman, Jennifer
AU - Feng, Kung-I
AU - Halbert, Gavin
AU - Kostewicz, Edmund
AU - McAllister, Mark
AU - Muenster, Uwe
AU - Thinnes, Julian
AU - Taylor, Robert
AU - Mullertz, Anette
N1 - Copyright © 2013 Elsevier B.V. All rights reserved.
PY - 2014/6/16
Y1 - 2014/6/16
N2 - 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.
AB - 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.
U2 - 10.1016/j.ejps.2013.10.015
DO - 10.1016/j.ejps.2013.10.015
M3 - Journal article
C2 - 24215735
VL - 57
SP - 173
EP - 199
JO - Norvegica Pharmaceutica Acta
JF - Norvegica Pharmaceutica Acta
SN - 0928-0987
ER -