Impact of drug release in USP II and in-vitro stomach on pharmacokinetic: The case study of immediate-release carbamazepine tablets

The in-vitro reproduction of the real physiological conditions that occur along the gastrointestinal (GI) tract would be the optimum for the dissolution and release testing of pharmaceutical formulations for oral intake. In this study a method for the automated reproduction of the real pH conditions that occurs in the gastric cavity and a device that mimics the same forces exerted by the internal walls of the stomach are presented. Commercial immediate-release carbamazepine tablets were tested in conventional (USP II) and unconventional apparatuses. The gastric pH and the fluid dynamic conditions are factors to be carefully considered since they both affect the drug release profiles. Finally, a PBPK model was used to predict the evolution of plasma drug concentrations knowing the experimental in-vitro GI release behav-ior. It was found that, for immediate-release carbamazepine tablet, the gastric drug release does not have a major impact on the plasmatic drug concentration. (c) 2022 Elsevier Ltd. All rights reserved.