Self-emulsifying
drug-delivery systems (SEDDS) have been extensively
shown to increase oral absorption of solvation-limited compounds.
However, there has been little clinical and commercial use of these
formulations, in large part because the demonstrated advantages of
SEDDS have been outweighed by our inability to precisely predict drug
absorption from SEDDS using current in vitro assays. To overcome this
limitation and increase the biological relevancy of in vitro assays,
an absorption function can be incorporated using biomimetic membranes.
However, the effects that SEDDS have on the integrity of a biomimetic
membrane are not known. In this study, a quartz crystal microbalance
with dissipation monitoring and total internal reflection fluorescence
microscopy were employed as complementary methods to in vitro lipolysis-permeation
assays to characterize the interaction of various actively digested
SEDDS with a liquescent artificial membrane comprising lecithin in
dodecane (LiDo). Observations from surface analysis showed that interactions
between the digesting SEDDS and LiDo membrane coincided with inflection
points in the digestion profiles. Importantly, no indications of membrane
damage could be observed, which was supported by flux profiles of
the lipophilic model drug felodipine (FEL) and impermeable marker
Lucifer yellow on the basal side of the membrane. There was a correlation
between the digestion kinetics of the SEDDS and the flux of FEL, but
no clear correlation between solubilization and absorption profiles.
Membrane interactions were dependent on the composition of lipids
within each SEDDS, with the more digestible lipids leading to more
pronounced interactions, but in all cases, the integrity of the membrane
was maintained. These insights demonstrate that LiDo membranes are
compatible with in vitro lipolysis assays for improving predictions
of drug absorption from lipid-based formulations.