Unintended physicochemical interaction of an excipient with a drug substance in a dosage form can result in the complexation or binding of the drug, resulting in slow and/or incomplete drug release in a dissolution medium. It is important to assess the risk whether such interactions would reduce oral bioavailability of a drug from its dosage form. This chapter describes the development of a methodology to assess the biorelevance of the drug release impact of drug-excipient binding interactions using a model compound, brivanib alaninate. This methodology was developed using a combination of modeling and simulation tools as well as experimental data generated in vitro and in vivo. In addition, general application of this principle and methodology to other drug substances and binding affinities of drugs

with excipients as a function of dose is described.