Early pharmaceutical profiling to predict oral drug absorption: Current status and unmet needs
| Autor: | Karl J. Box, Sara B. E. Andersson, Søren Astrup Jørgensen, Uwe Muenster, Per Artursson, Kung I. Feng, Jennifer B. Dressman, Anette Müllertz, Mark McAllister, Christel A. S. Bergström, Edmund Kostewicz, René Holm, Stefania Beato, Anders Borde, Robert Taylor, Julian Thinnes, Marcus E. Brewster, Gavin Halbert |
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| Rok vydání: | 2014 |
| Předmět: |
Chemistry
Pharmaceutical Administration Oral Pharmaceutical Science Pharmacology Models Biological Intestinal absorption Biopharmaceutics Excipients Pharmacokinetics In vivo Animals Humans Technology Pharmaceutical Medicine Profiling (information science) Computer Simulation Pharmaceutical sciences Active ingredient Gastric Juice Intestinal Secretions business.industry Hydrogen-Ion Concentration Gastrointestinal Tract Biopharmaceutical Intestinal Absorption Pharmaceutical Preparations Solubility Biochemical engineering business Oral retinoid |
| Zdroj: | European Journal of Pharmaceutical Sciences. 57:173-199 |
| ISSN: | 0928-0987 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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