Adequatedrug solubility in the gastrointestinal tract is essential for systemic therapyof orally administered medications. To carry out research on the solubility ofpoorly soluble drugs in vitro, simulated intestinal fluid (SIF) is usedin place of human intestinal fluid (HIF). However, typical SIF reflects averagecompositions of HIF rather than the full range of compositions previouslyreported. This study examines a new suite of SIF media (based on variabilityobserved in HIF) to explore the range of solubility of four poorly soluble drugs(Naproxen, Indomethacin, Phenytoin and Tadalafil) in the fasted state.