["Drug-excipient binding can affect in-vitro drug release. Literature suggests that drug-excipient ionic binding interaction that is not disrupted by physiological salt concentration in the dissolution medium can impact a drug's oral bioavailability. We investigated whether nondisruption of interaction by physiological salt concentration was an adequate predictor of its biorelevance using the binding of a model amine high dose drug brivanib alaninate (BA) to croscarmellose sodium (CCS) as an example.", 'BA was formulated into an immediate release tablet using CCS as disintegrant by a wet granulation process. In-vitro drug release was carried out as a function of pH and buffer concentration of the medium. BA-CCS binding was studied in buffer solution and data fitted to a Langmuir isotherm. A simulation model and an isothermal titration calorimetry method were developed to assess the bioavailability risk and strength of drug-excipient binding interaction, independent of physiological salt concentration consideration.', "BA-CCS binding was pH-dependent, reversible, ionic, and not disrupted by increasing the buffer concentration in the dissolution medium. Absorption simulation predictions of no effect of CCS binding on BA's bioavailability were confirmed by a monkey pharmacokinetic study."] Does reversible and pH-dependent weak drug-excipient binding affect oral bioavailability of high dose drugs?