In Vivo Toxicology of Excipients Commonly Employed in Drug Discovery in Rats

Introduction: Toxicology and pharmacology studies conducted in the early stages of drug discovery often require formulation strategies involving the use of excipients with limited knowledge regarding their preclinical safety liabilities. The use of excipients is vital to efforts to solubilize and deliver small molecules in drug discovery. Whilst excipients can have a significant impact on pharmacology and toxicology studies by enabling solubility to maximize systemic exposure, they also have the potential to obscure clinical pathology endpoints. In this article, we report on the in vivo safety in rats for 18 excipients commonly employed in formulations for preclinical pharmacology and toxicology studies.

Methods: The test articles were administered once daily for five days, by oral gavage to male Sprague Dawley rats, and the animals monitored for visible clinical signs. At the end of the study, routine necropsy and clinical pathology endpoints were investigated.

Results: None of the excipients tested were acutely toxic. However, there were effects on parameters commonly evaluated as indicators of health and/or toxicological response in regulated preclinical safety studies.

Discussion: While the excipients tested were generally well tolerated, several were found to affect common clinical pathology endpoints in a manner that might confound or conceivably mask the interpretation of compound mediated adverse/pharmacological effects.