Mimicking the contractions of a human stomach and their effect on pharmaceuticals

The prediction of the drug's fate, once it is released from a pharmaceutical form, is one of the key topic in pharmaceutics and, to evaluate its release kinetics and effectiveness, the reproduction of the mixing conditions experienced by the pharmaceutical system is necessary. In this work a device reproducing the peristaltic waves of the stomach is presented, in order to obtain more reliable drug release profiles. Extended release commercial tablets of diclofenac were tested using both the conventional dissolution method and the new in vitro model proposed. The release profiles obtained using the conventional method and using the artificial stomach were found different both in shape and in magnitude. In particular, a drug concentration gradient along the stomach was realized, reflecting the poor mixing behavior in the model, similarly to what happen in the real physiology. Furthermore, also during the second stage of dissolution the evolutions were different, probably due to the higher shear experienced by the tablet during the first stage in the novel apparatus. The plasma concentration evolutions were predicted by a pharmacokinetic model starting from in vitro dissolution profiles. The comparison of the plasma concentrations confirmed that the dissolution kinetics strongly influences the drug evolution in the human body.