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A Critical Overview of the Biological Effects of Excipients (Part I): Impact on Gastrointestinal Absorption

  • Review Article
  • Theme: The Biological Effect of Pharmaceutical Excipients
  • Published:
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Abstract

Traditionally, excipients have been considered in drug development from the perspective of their influence on drug solubility, manufacturability, and ability to control in vitro and in vivo drug release. These effects have been largely evaluated through studies involving in vitro dissolution methods. However, there is a growing awareness that what had previously been considered biologically inert excipients can exert numerous in vivo effects. This includes the potential to change gastrointestinal (GI) transit time, enterocyte passive transcellular or paracellular permeability, active transport activity, or presystemic drug metabolism. In this critical overview of the biological effects of excipients (Part I), we provide a summary of select published studies that explore these various in vivo factors. We also include a table that points readers to published reviews that list a range of excipients known to have biological activity. A subsequent discussion on in vitro, in vivo, and in silico methods that can be used to explore these excipient effects is provided in a separate (Part 2) continuation of this critical overview.

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Authors and Affiliations

  1. Office of New Animal Drug Evaluation, Center for Veterinary Medicine, U.S. Food and Drug Administration (FDA), Rockville, Maryland, USA

    Marilyn N. Martinez

  2. Pion Inc, Billerica, Maryland, USA

    Balint Sinko

  3. Division of Quantitative Methods and Modeling (DQMM), Office of Research and Standards (ORS), Office of Generic Drugs (OGD), Center for Drug Evaluation and Research (CDER), FDA, Silver Spring, Maryland, USA

    Fang Wu & Eleftheria Tsakalozou

  4. UCB Pharma S.A. Allée de la Recherche, 60 1070, Brussels, Belgium

    Talia Flanagan

  5. Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 3 Muegyetem rakpart, Budapest, 1111, Hungary

    Enikő Borbás

  6. Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA

    Kathleen M. Giacomini

Authors
  1. Marilyn N. Martinez
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  2. Balint Sinko
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  3. Fang Wu
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  4. Talia Flanagan
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  5. Enikő Borbás
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  6. Eleftheria Tsakalozou
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  7. Kathleen M. Giacomini
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Contributions

Manuscript conceptualization: Marilyn Martinez, Fang Wu, and Balint Sinko.

Manuscript development lead: Marilyn Martinez.

Manuscript development co-leads: Fang Wu and Balint Sinko.

Introduction and conclusion: Marilyn Martinez, Fang Wu, and Balint Sinko.

Excipient effects on intestinal transit time: Marilyn Martinez and Talia Flanagan.

Excipient effect on passive transport: Balint Sinko and Enikő Borbás.

Effect of excipients on active transporters: Eleftheria Tsakalozou and Kathleen Giacomini.

Excipient effects on metabolism: Talia Flanagan.

Species-excipient relationships: Marilyn Martinez.

Points to ponder: All co-authors.

Corresponding author

Correspondence to Marilyn N. Martinez.

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Conflict of Interest

The authors declare no competing interests.

Disclaimer

The contents of this manuscript reflect the views of the authors and should not be construed to represent FDA’s views or policies.

Additional information

Guest Editors: Marilyn N. Martinez, Balint Sinko and Fang Wu

Marilyn N. Martinez, Balint Sinko and Fang Wu are Guest Editors for the theme issue on the Biological Effects of Excipients.

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Martinez, M.N., Sinko, B., Wu, F. et al. A Critical Overview of the Biological Effects of Excipients (Part I): Impact on Gastrointestinal Absorption. AAPS J 24, 60 (2022). https://doi.org/10.1208/s12248-022-00711-3

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  • DOI: https://doi.org/10.1208/s12248-022-00711-3

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