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
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.
KW - administration, oral
KW - animals
KW - biopharmaceutics
KW - chemistry, pharmaceutical
KW - computer simulation
KW - excipients
KW - gastric juice
KW - gastrointestinal tract
KW - humans
KW - hydrogen-ion concentration
KW - intestinal absorption
KW - intestinal secretions
KW - models, biological
KW - pharmaceutical preparations
KW - pharmacokinetics
KW - solubility
KW - technology, pharmaceutical
KW - preformulation
KW - physicochemical properties
KW - pharmaceutical profiling
KW - biorelevant media
KW - intestinal fluid
KW - absorption
UR - http://www.sciencedirect.com/science/journal/09280987
U2 - 10.1016/j.ejps.2013.10.015
DO - 10.1016/j.ejps.2013.10.015
M3 - Article
C2 - 24215735
SN - 0928-0987
VL - 57
SP - 173
EP - 199
JO - European Journal of Pharmaceutical Sciences
JF - European Journal of Pharmaceutical Sciences
ER -