@article{3060971,
    title = "In vitro models for the prediction of in vivo performance of oral dosage forms",
    author = "Kostewicz, E.S. and Abrahamsson, B. and Brewster, M. and Brouwers, J. and Butler, J. and Carlert, S. and Dickinson, P.A. and Dressman, J. and Holm, R. and Klein, S. and Mann, J. and McAllister, M. and Minekus, M. and Muenster, U. and Müllertz, A. and Verwei, M. and Vertzoni, M. and Weitschies, W. and Augustijns, P.",
    journal = "EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES",
    year = "2014",
    volume = "57",
    number = "1",
    pages = "342-366",
    publisher = "Elsevier",
    issn = "0928-0987",
    doi = "10.1016/j.ejps.2013.08.024",
    keywords = "albendazole;  amprenavir;  bile acid;  celecoxib;  cinnarizine;  cyclodextrin;  danazol;  diclofenac;  dipyridamole;  excipient;  gelucire;  ketoconazole;  loviride;  montelukast;  octanol;  propranolol;  saquinavir;  drug;  drug dosage form, controlled drug release;  drug absorption;  drug bioavailability;  drug development;  drug dosage form;  drug formulation;  drug penetration;  drug solubility;  gastrointestinal motility;  human;  hydrodynamics;  in vitro study;  in vivo study;  lipolysis;  nonhuman;  precipitation;  prediction;  priority journal;  quality control;  review;  simulation;  tablet disintegration;  bioavailability;  biological model;  chemistry;  drug dosage form;  intestine;  intestine absorption;  medical literature;  metabolism;  oral drug administration;  permeability;  pharmaceutics;  pharmacokinetics;  procedures;  solubility, Administration, Oral;  Biological Availability;  Biopharmaceutics;  Dosage Forms;  Gastrointestinal Motility;  Humans;  Intestinal Absorption;  Intestines;  Models, Biological;  Permeability;  Pharmaceutical Preparations;  Pharmacokinetics;  Pharmacopoeias as Topic;  Solubility",
    abstract = "Accurate prediction of the in vivo biopharmaceutical performance of oral drug formulations is critical to efficient drug development. Traditionally, in vitro evaluation of oral drug formulations has focused on disintegration and dissolution testing for quality control (QC) purposes. The connection with in vivo biopharmaceutical performance has often been ignored. More recently, the switch to assessing drug products in a more biorelevant and mechanistic manner has advanced the understanding of drug formulation behavior. Notwithstanding this evolution, predicting the in vivo biopharmaceutical performance of formulations that rely on complex intraluminal processes (e.g. solubilization, supersaturation, precipitation...) remains extremely challenging. Concomitantly, the increasing demand for complex formulations to overcome low drug solubility or to control drug release rates urges the development of new in vitro tools. Development and optimizing innovative, predictive Oral Biopharmaceutical Tools is the main target of the OrBiTo project within the Innovative Medicines Initiative (IMI) framework. A combination of physico-chemical measurements, in vitro tests, in vivo methods, and physiology-based pharmacokinetic modeling is expected to create a unique knowledge platform, enabling the bottlenecks in drug development to be removed and the whole process of drug development to become more efficient. As part of the basis for the OrBiTo project, this review summarizes the current status of predictive in vitro assessment tools for formulation behavior. Both pharmacopoeia-listed apparatus and more advanced tools are discussed. Special attention is paid to major issues limiting the predictive power of traditional tools, including the simulation of dynamic changes in gastrointestinal conditions, the adequate reproduction of gastrointestinal motility, the simulation of supersaturation and precipitation, and the implementation of the solubility-permeability interplay. It is anticipated that the innovative in vitro biopharmaceutical tools arising from the OrBiTo project will lead to improved predictions for in vivo behavior of drug formulations in the GI tract. © 2013 Elsevier B.V. All rights reserved."
}