*2.9. Dynamic In Vitro Lipolysis of SEDDS*

Dynamic one-compartment in vitro lipolysis was carried out under human fasted-state conditions, as previously described [38–40]. Nonloaded Citrem and Standard SEDDS both without and with the addition of orlistat 0.25% (*w*/*w*) were tested. The addition of orlistat, a lipase inhibitor, into the SEDDS composition has previously been described to inhibit the digestion of SEDDS [41]. SEDDS (0.5 g) was added into a temperature-controlled vessel containing fasted-state simulated intestinal fluid (FaSSIF) used as the lipolysis medium (2.95-mM bovine bile, 0.26-mM soy phospholipids, 2.0-mM maleic acid, 2.0-mM Tris, 50.0-mM NaCl and 1.4-mM CaCl2, adjusted to pH 6.5). The digestion of the lipids was initiated by the addition of 5 mL of pancreatin solution with a final activity of 500 USP units/mL. The pancreatin solution was prepared by combining the appropriate amount of porcine pancreatin and adding intestinal lipolysis medium. The resulting suspension was vortexed and centrifuged (7 min, 6500× *g*). pH 6.5 was maintained by an automated pH stat (Metrohm Titrino 744, Tiamo Version 1.3, Herisau, Switzerland), as the released free fatty acids were continuously titrated by 0.4-M NaOH. The lipolysis was performed for 60 min in three independent experiments (*n* = 3).
