Exposure assessment

Abstract

Excipients embrace a diverse group of chemicals that are incorporated into pharmaceutical dosage forms for a variety of purposes. Typically, products contain multiple excipients (Table 1). Each excipient has been selected for its functionality, and it has been deemed safe in the particular application and compatible with other components of the formulation. Pharmaceutical excipients are, by design, devoid of significant pharmacological or toxicological activity at the doses used in drug product formulations, and they are completely lacking predictable teratogenic and carcinogenic potential. The safety of individual excipients is paramount. Compounds with narrow safety margins are seldom, if ever, employed as excipients. Thus, excipients are exceptionally safe, but similar to all chemicals, cannot be assumed to be toxicologically inert in every situation (l–4). Examples of the potential toxicity of representative excipients are provided in Table 2. The dose of an excipient administered to humans is usually selected initially as some fraction of a safe animal dose. However, the dose levels of an excipient used in chronic animal toxicity studies are selected based partly on the projected human dose and dosage schedule. Accordingly, beyond acute animal toxicology studies, the testing of new excipients usually occurs concurrently in humans and animals; the results from animal studies help guide the design of human studies and vice versa (5,6). Therefore, in the early stages of development, a provisional human exposure assessment is usually undertaken. This assessment undergoes