PBPK models for the prediction of in vivo performance of oral dosage forms

Kostewicz, Edmund; Aarons, Leon; Bergstrand, Martin; Bolger, Michael B.; Galetin, Aleksandra; Hatley, Oliver; Jamei, Masoud; Lloyd, Richard C.; Pépin, Xavier; Rostami‐Hodjegan, Amin; Sjögren, Erik; Tannergren, Christer; Turner, David B.; Wagner, Christian; Weitschies, Werner; Dressman, Jennifer B.

doi:10.1016/j.ejps.2013.09.008

Cited by 284 publications

(218 citation statements)

References 211 publications

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“…Several factors have been reported to influence the absorption and activity of colon delivered drugs, including low volume and high viscosity and low volume of colonic fluids (challenging drug dissolution), colonic pH (the colonic pH varies across the different segments of the colon and this can affect the pharmacokinetic and pharmacodynamics of drugs), the presence of bacteria (which produce different enzymes able to metabolize drugs and to induce the formation of active or inactive metabolites) and the colonic transit time (which can modify the bioavailability of drugs as such) (Amidon et al, 2015;Kostewicz et al, 2014a).…”

Section: Invasive Methodologiesmentioning

confidence: 99%

Exploring gastrointestinal variables affecting drug and formulation behavior: Methodologies, challenges and opportunities

Hens

Corsetti

Spiller

et al. 2017

International Journal of Pharmaceutics

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(2017) Exploring gastrointestinal variables affecting drug and formulation behavior: methodologies, challenges and opportunities. International Journal of Pharmaceutics, 519 (1-2). pp. 79-97. ISSN 1873-3476Access from the University of Nottingham repository: http://eprints.nottingham.ac.uk/39960/1/FinalVersion-Revised-FOR_EPRINTS_1_YEAR_EMBARGO_ELSEVIER.pdf Copyright and reuse:The Nottingham ePrints service makes this work by researchers of the University of Nottingham available open access under the following conditions. This article is made available under the Creative Commons Attribution Non-commercial No Derivatives licence and may be reused according to the conditions of the licence. For more details see: http://creativecommons.org/licenses/by-nc-nd/2.5/ A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription. After oral intake, a drug formulation is challenged by several gastrointestinal (GI) barriers. Complex variables such as pH, GI secretions and GI transit/motility along the GI tract can affect drug release and absorption in a positive or negative way depending on the physicochemical properties of the drug compound (e.g. pH/pKa interplay for ionizable drugs) and/or the formulation characteristics (e.g. pHsensitive coating). In addition, inter-subject variability in characteristics of the GI environment may cause variable drug absorption and systemic drug availability (Riethorst et al., 2015). Determining the median and range for specific GI variables, and understanding how they influence oral drug behavior along the GI tract, will be helpful in the field of drug development. 2The present review provides an overview of different methodologies that can be applied to study physiological variables of the human GI tract and their impact on oral drug absorption in healthy and patient populations. The methodologies have been subdivided into two groups: (i) noninvasive and (ii) invasive methodologies. Although some of the methodologies are more historical than operational, they have been of paramount importance for innovations in drug and formulation development; in addition, they have created the basis for several novel methodologies, leading to an in-depth comprehension of different GI variables: gastric emptying (magnetic resonance imaging (MRI), scintigraphy, acetaminophen absorption technique, ultrasonography, breath test, intraluminal sampling and telemetry), motility (MRI, small intestinal/colonic manometry and telemetry), GI volume changes (MRI and ultrasonography), temperature (telemetry) and GI pH (intraluminal sampling and telemetry). Noninvasive methodologiesa. Scintigraphy Disturbances in the normal movement of food along the GI tract can be associated with abdominal pain, early satiety and nausea. Measurement of GI transit, es...

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Section: Invasive Methodologiesmentioning

confidence: 99%

Exploring gastrointestinal variables affecting drug and formulation behavior: Methodologies, challenges and opportunities

Hens

Corsetti

Spiller

et al. 2017

International Journal of Pharmaceutics

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“…This model is based on the assumption that the drug in vivo delivery profile may be assessed by combining the drug physicochemical and biopharmaceutical properties with the physiological parameters. It can include all the major processes relevant to drug absorption and elimination, such as nonlinear dose-dependent absorption, first pass metabolism in gut and liver, presence of a limited absorption window for the compounds whose absorption is dependent on influx transporters with narrow regional expression in gut (7,20).…”

Section: Gastrointestinal Simulationmentioning

confidence: 99%

“…The advanced knowledge gained about the interplay of different factors influencing drug absorption has fostered the development of predictive models for oral drug absorption such as physiologically based pharmacokinetic models (6, 7) and physiologically relevant in vitro dissolution methods (8). Integration of in vitro and in silico approaches is expected to accelerate drug development and improve clinical product performance (7,8). Depending on the method of analysis employed, different in vivo drug delivery profiles (iDDP) may result.…”

mentioning

confidence: 99%

Deciphering nifedipine in vivo delivery from modified release dosage forms: Identification of food effect

2015

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With the increased reliance on in vitro dissolution testing as an indicator of in vivo drug behavior and the trend towards the in silico modeling of dosage form performance, the need for bioperformance dissolution methodology development has been enhanced. Determination of the in vivo drug delivery profile is essential for the bioperformance dissolution test development and in vitro/in vivo correlation modeling, as well as the understanding of absorption mechanisms. The aim of this study was to compare different methods in terms of their usefulness and applicability in deciphering in vivo delivery of nifedipine administered in modified release dosage forms. A detailed survey of publications on nifedipine pharmacokinetics was done and used to identify the magnitude of food effect. In vitro dissolution testing was performed under various experimental conditions. Obtained results indicate the potential for using the developed in silico model coupled with discriminative in vitro dissolution data for identification of the in vivo drug product behavior

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“…Prof. Dr. Bertil Abrahamson spoke about the Oral Biopharmaceutics Tools (OrBiTo) Project showing the four Work Packages (9)(10)(11). OrBiTo is a partnership among pharmaceutical companies, universities, and commercial PBPK software development companies, whose main goal is to improve tools to predict the performance of orally administered drugs.…”

Section: The Presentationsmentioning

confidence: 99%

Meeting Report: International Workshop on Implementation of Biowaivers Based on the Biopharmaceutics Classification System (BCS)

Cristofoletti¹,

Shah²,

Langguth³

et al. 2015

Dissolution Technol.

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PBPK models for the prediction of in vivo performance of oral dosage forms

Cited by 284 publications

References 211 publications

Exploring gastrointestinal variables affecting drug and formulation behavior: Methodologies, challenges and opportunities

Exploring gastrointestinal variables affecting drug and formulation behavior: Methodologies, challenges and opportunities

Deciphering nifedipine in vivo delivery from modified release dosage forms: Identification of food effect

Meeting Report: International Workshop on Implementation of Biowaivers Based on the Biopharmaceutics Classification System (BCS)

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