ABSTRACT
The development of excipientmaterials for use in drug formulations represents a growing area of interest (and of invested time and cost) for pharmaceutical companies. Such development has been fuelled by the increasing need for more sophisticated excipients and/or new uses for established ones. However, a key consideration is how safe the material is. Answering such a question is vital, especially because pharmaceutical excipients can no longer be regarded as totally inert/inactive substances within the formulation of pharmacologically active drugs. New drug development itself involves a range of preclinical studies to show efficacy (pharmacology investigations) and safety (kinetic and toxicology studies) to support clinical trial work and eventual product licensing. Safety studies can include adsorption, distribution, metabolism, and excretion (ADME)/pharmacokinetic (PK), general toxicity, reproduction toxicity, genotoxicity, and carcinogenicity investigations. Additionally other specific studies, for example, local tolerance investigations for drugs administered by the topical or inhalation route, or immunological evaluation for biological drugs may be needed. Safety pharmacology studies (which examine for unexpected high-dose pharmacological effects) can also be considered as part of the safety package. Obviously, pharmacological evaluation per se is not the norm for excipient materials. However, evaluation for potential toxicity is vital, and this chapter examines the safety evaluation process for excipients (new, ‘‘essentially’’ new, and established) from a preclinical perspective and shows that the role of the toxicologist is indeed a challenging one.
