​This study applies biorelevant fasted and fed simulated intestinal media (SIM) to compare the solubility of griseofulvin, ibuprofen, and dipyridamole to investigate the prediction of food effects. These media cover over 90% of the human intestinal fluid variation in each state providing a comprehensive solubility range in vitro. The results highlight that ibuprofen is unaffected by food but dipyridamole and griseofulvin show an increased solubility in the fed state, suggesting positive food effects in line with in vivo literature data. Drugs with solubility limited absorbable dose (SLAD) lower or close to the oral dose are more likely to present a food effect, thus SLAD analysis could aid the prediction of food effects. This approach may be applied in early drug development as a preliminary prediction tool.​