Introduction: The development of poorly soluble or permeable new chemical entities within the pharmaceutical industry often requires the use of nonstandard enabling nonclinical oral formulations. Despite this, the toxicity profile of many commonly used nonclinical vehicles is poorly understood. This lack of data can lead to unexpected formulation-related effects being observed in critical oral safety studies.
Areas covered: This article summarizes the key considerations for formulation selection for oral nonclinical safety studies, and provides a strategy for appropriate development-phase formulation selection. The industry's use of oral nonclinical vehicles is reviewed, based on data from the FDA's Orange Book. Finally, a summary of the repeat dose oral toxicity of commonly used vehicles is presented.
Expert opinion: The rapid identification of a suitable nonclinical oral formulation is a critical step in small-molecule drug development. In order to maintain flexibility and address the needs of a diverse set of new chemical entities (NCEs) with widely varying physiochemical properties, a "tool belt" of multiple oral formulations is recommended. The appropriate formulation is identified based on the goals of the study, as well as exposure required, species, duration and therapeutic indication of the NCE.