In vitro-in vivo-in silico approach in biopharmaceutical characterization of ibuprofen IR and SR tablets

Sofija Beloica, Sandra Cvijić, Marija Bogataj, Jelena Parojčić

Within the last decades, physiologically based pharmacokinetic models have emerged into a biopharmaceutical toolkit that has been proven useful in understanding how physicochemical, formulation and physiological factors affect oral drug absorption. The purpose of this study was to develop a drug specific physiologically based pharmacokinetic model that will allow mechanistic interpretation of oral absorption from dosage forms exhibiting different in vitro and different in vivo performance (i.e. immediate release and sustained release tablets) and identification of bioperformance dissolution testing. Ibuprofen was chosen to be used for the "proof of concept" considering it is well characterised and the necessary physicochemical, biopharmaceutical and pharmacokinetic properties for model development could be found in the literature. Gastrointestinal simulation technology implemented in Simcyp(®) was successful in estimating ibuprofen oral absorption. The developed model exhibited good generalisation ability for the dosage forms studied. The obtained results indicate that the model was sensitive to input kinetics represented by the in vitro drug release profiles obtained under various dissolution conditions. According to the obtained results, reciprocating cylinder apparatus with biorepresentative change in media pH might be considered as bioperformance dissolution in the case of the two ibuprofen sustained release products studied. These results further justify the use of integrated in vitro-in vivo-in silico approach in estimating bioperformance of oral solid dosage forms.