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

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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About this article: 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

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

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 vivodrug release. These effects have been largely evaluated through studies involving in vitrodissolution 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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