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 -