Profound effects of gastric secretion rate variations on the precipitation of erlotinib in duodenum - An in vitro investigation.

Using an artificial stomach and duodenum (ASD), we investigated the pH-dependent precipitation of erlotinib (ERL) during dissolution in the gastrointestinal (GI) tract by varying the rate of gastric fluid secretion (RGFS). Results show that decreasing RGFS from 2.5 to 0.5 mL/min leads to an increased degree of supersaturation in the duodenum fluid due to elevated pH, resulting in precipitation of ERL and a reduced area under the curve (AUC) of the concentration - time profiles from 14,000 to 3,000 (μg‧min)/mL. Such a change in AUC is expected to lower the bioavailability of ERL, a BCS II drug, in patients with a low RGFS. This example demonstrates the potential use of ASD as an effective tool for guiding the efficient development of robust tablet formulations by better understanding the impact of GI tract pH on the fate of drugs in the duodenal fluid.