In Vitro Simulation of Human Digestion: Chemical and Mechanical Behavior

The drug release pattern from an orally administrated pharmaceutical dosage form can be significantly affected by simultaneous food intake and drug administration due to the changes in the gastrointestinal physiology, in particular because of the pH profile evolution and of the mixing conditions. In this work, the release from a commercial diclofenac tablet subjected to the pH conditions experienced by the gastrointestinal tract in fed conditions was analyzed and then compared with the release pattern obtained using a conventional dissolution method. The tablets behaved differently because of the partial dissolution of the coating due to high pH values in the first stage of the dissolution method, which takes into account the fed-state conditions. Tablets composed of a homemade enteric polymer loaded with diclofenac overcame this drawback. Moreover, an in vitro device mimicking peristaltic contractions in the stomach was proposed, and the release pattern from commercial tablets was compared with that obtained under conventional dissolution conditions. The release pattern was strongly influenced by the hydrodynamics. The two experimental setups (pH and peristalsis simulations) demonstrate that a gastrointestinal reproduction closer to the real physiology is necessary to achieve an accurate and reliable prediction of the behavior of pharmaceuticals.