Potential Impact of Cyclodextrin-Containing Formulations in Toxicity Evaluation of Novel Compounds in Early Drug Discovery

Cyclodextrins (CDs) are widely used as enabling excipients to improve in vivo drug delivery. The ability of CDs to form inclusion complexes with drugs and thereby improving solubility and stability of drugs is well established, and has been successfully used for several drugs on the market. Combined with well established preclinical and clinical safety profiles for selected CDs, they are of interest as excipients in preclinical and clinical stages of drug development. Another feature of CDs is their demonstrated ability to mitigate local toxicities of drugs. While this feature makes them attractive from a clinical drug delivery perspective, it may not be ideal from a preclinical toxicology evaluation perspective when the new chemical entities have intrinsic irritant or cytotoxic characteristics, which may be shielded by CDs. Herein, we review use of CDs in pharmaceuticals, focusing on their potential to mitigate toxicities of compounds, and suggest that, this very potential may undermine toxicity evaluation, especially by oral route, of novel compounds during early drug discovery.