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A Critical Overview of the Biological Effects of Excipients (Part II): Scientific Considerations and Tools for Oral Product Development

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

It is now recognized that a number of excipients previously considered to be “inert” have the capacity to alter drug oral bioavailability through a range of in vivo effects. The various mechanisms through which an excipient can affect in vivo gastrointestinal physiology and drug absorption characteristics were explored in “A Critical Overview of The Biological Effects of Excipients (Part I): Impact on Gastrointestinal Absorption.” The next critical issue that needs to be discussed is how these biological effects are evaluated. Therefore, in Part 2 of this critical overview, the in vitro, in vivo, and in silico methods for evaluating excipient effects are considered. Examples are provided to illustrate how such studies employing these various procedures have been used to promote formulation understanding and optimization. Finally, a discussion of how the Center for Drug Evaluation and Research applies these tools to support biowaivers is provided.

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Authors and Affiliations

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

    Marilyn N. Martinez

  2. 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

  3. Pion Inc, 10 Cook Street, Billerica, Maryland, 01821, USA

    Balint Sinko

  4. School of Veterinary Medicine and UCD Conway Institute, University College Dublin, Belfield, Dublin, D04 V1W8, Ireland

    David J. Brayden

  5. Lonza Small Molecules R&D, 64550 Research Rd, Bend, Oregon, 97701-8583, USA

    Michael Grass & Aaron Stewart

  6. Pharmaceutical Sciences and Clinical Supply, Merck & Co., Inc, Rahway, New Jersey, USA

    Filippos Kesisoglou

  7. Sage Therapeutics, 215 First Street, Cambridge, MA, 02142, USA

    Aaron Stewart

  8. Molecular Pharmaceutics Lab, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1, Noji-higashi, Kusatsu, Kyoto, Shiga, 525-8577, Japan

    Kiyohiko Sugano

Authors
  1. Marilyn N. Martinez
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  2. Fang Wu
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  3. Balint Sinko
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  4. David J. Brayden
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  5. Michael Grass
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  6. Filippos Kesisoglou
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  7. Aaron Stewart
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  8. Kiyohiko Sugano
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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: Marilyn Martinez, Fang Wu, Balint Sinko, David Brayden, Aaron Stewart, and Michael Glass.

In vitro test selection for bioavailability-enhancing formulations: David J. Brayden, Michael Grass, and Aaron Stewart.

Using in silico models of API-excipient interactions to inform formulation development: Filippos Kesisoglou.

Considerations for the development of predictive models describing the impact of excipients on the rate and extent of oral drug absorption: Michael Grass, Aaron Stewart, and Kiyohiko Sugano.

How might excipients impact bioequivalence assessments of human generic drug products: Fang Wu.

Conclusion: Marilyn Martinez, Fang Wu, and Balint Sinko.

Corresponding author

Correspondence to Marilyn N. Martinez.

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Conflict of Interest

The authors have no relevant financial or non-financial interests to disclose.

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.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Marilyn N. Martinez, Fang Wu, and Balint Sinko are co-editors for the theme issue on “The Biological Effects of Excipients.”.

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Martinez, M.N., Wu, F., Sinko, B. et al. A Critical Overview of the Biological Effects of Excipients (Part II): Scientific Considerations and Tools for Oral Product Development. AAPS J 24, 61 (2022). https://doi.org/10.1208/s12248-022-00713-1

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