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.
Keywords: GI transit time; active transport; drug metabolism; excipient effects; membrane permeability.
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