Application of the Dynamic Gastric Model to evaluate the effect of food on the drug release characteristics of a hydrophilic matrix formulation.

Characterisation of the effect of food on the bio-performance of modified and extended release dosage forms can be very challenging due to the need to replicate the dynamic biochemical conditions of the human gut as well as the complex physical processing modalities under fed state. Classical compendial methods are useful for testing the quality of pharmaceutical dosage forms but typically have limitations in the accurate prediction of food-effect in-vivo. Preliminary evaluation of the Dynamic Gastric Model (DGM) shows that it can provide substantially more detailed mechanistic information on dosage form properties compared to conventional compendial testing. The potential effect of food on the drug release and physical properties of a hydrophilic matrix formulation containing a model drug, hydrochlorothiazide, was studied using compendial methods, bio-relevant media and the DGM (in combination with an off-line intestinal model). Whilst the compendial methods with biorelevant media provided good correlation with the dissolution rates observed using the DGM/intestinal model under simulated fasted state, the quantification of simulated fed state performance changes was much more challenging using the compendial methods. Classical compendial studies using biorelevant FeSSIF and FaSSIF media could not readily discern differences in dissolution performance under fasted and fed states; however, the DGM could detect significant changes in both physical properties as well as drug release performance under fed state processing.