Tiny-TIM intestinal fluids versus human intestinal fluids: A comparison of their composition and solubilizing capacity for poorly soluble drugs

The tiny-TIM system offers an in vitro platform for the simulation of physiological processes occurring in human stomach and small intestine aiding in drug product development by predicting the bioperformance of oral formulations under fasted and fed state intake conditions. To assess this in vitro system in terms of its physiological relevance, we performed a detailed analysis of the composition as well as the solubilizing capacity of tiny-TIM intestinal fluids (TIF), and compared this to previously collected and analysed human intestinal fluids (HIF). Moreover, the impact of meal type on TIF composition and solubilising capacity was investigated by using either a liquid meal or a solid meal. In the fasted state, TIF exhibited lower lipid concentrations with a TIF/HIF ratio of 0.27, and elevated bile salt levels (TIF/HIF ratio of 1.8). Fasted state TIF generally overpredicted the solubilizing capacity of HIF, likely due to its higher bile salt concentrations. In the fed state, TIF contained biorelevant lipid concentrations but remained monophasic without phase separation, unlike HIF. This was likely due to higher bile salt levels (5.3 times that of HIF), which solubilized all lipids into the micellar phase. This resulted on average in a 3.3-fold increase in solubility of the poorly water-soluble model compounds in the micellar fraction of TIF as compared to HIF. Shifting from a liquid to a solid meal had minimal impact on TIF composition and solubilizing capacity.