The formation of lipid digestion products is a relevant parameter for effective in vivo performance of self-emulsifying drug delivery systems (SEDDS). These lipid-based formulations contain non-ionic surfactants, therefore the effects of polysorbate 80 (PS 80), D-alpha-tocopheryl polyethylene glycol (1000) succinate (TPGS), Surfhope((R)) sugar ester D-1216 (sucrose laurate), Cremophor EL (Cr EL) and Cremophor RH 40 (Cr RH 40) on triglyceride digestion by pancreatic lipases were tested in vitro using olive oil as model substrate. The IC(50) determined are 0.13mM (PS 80), 0.08mM (TPGS), 0.46mM (sucrose laurate), 0.19mM (Cr EL) and 0.04mM (Cr RH 40). The extent of inhibitory action is ranked in downward order: Cremophor RH 40>TPGS>polysorbate 80>Cremophor EL>sucrose laurate. The effects already occur below the critical micelle concentrations (CMC) of the detergents. At low concentrations of polysorbate 80 the inhibition shows a competitive mechanism. Furthermore, degradation by pancreatic enzymes of the surfactants themselves had been tested which also can affect the solubilization capacity of the intestinal fluid after administration of a SEDDS. Polysorbate 80, Cremophor EL and Cremophor RH 40 were shown to be susceptible to digestion by pancreatic enzymes. Fatty acid esters of polysorbate 80 were hydrolyzed with an extent of 14% (+/-1.0%). 14.4% (+/-3.3%) in case of Cremophor EL had been hydrolyzed, whereas Cremophor RH 40 had been degraded to a lower extend of 6.1% (+/-2.8%). TPGS and sucrose laurate appeared to be stable in present of pancreatic enzymes.