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Updated: Jun 28, 2026

In vitro Digestion of Emulsions in a Single Droplet via Multi Subphase Exchange of Simulated Gastrointestinal Fluids
Published on: November 18, 2022
Colloidal structures in media simulating intestinal fed state conditions with and without lipolysis products
Dimitrios G Fatouros1, Isabelle Walrand, Bjorn Bergenstahl
1Department of Pharmaceutics and Analytical Chemistry, The Faculty of Pharmaceutical Science, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark. df@dfuni.dk
Purpose:
To study the ultrastructure of biorelevant media and digestion products of self-nanoemulsifying drug delivery system (SNEDDS) at high level BS/PL conditions.
Methods:
Cryogenic transmission electron microscopy (Cryo-TEM) was employed to visualize the colloid structures in the biorelevant media and lipolytic products generated during hydrolysis of a SNEDDS formulation. Their electrical properties were investigated by measuring their zeta-potential values.
Results:
In the biorelevant media, vesicles (either unilamellar or multilamellar) and bilayer fragments are visualized. Occasionally, vesicles with an internal deformed structure are recognized, suggesting surface tension or uneven lateral stress. Visualization studies of the intermediate colloidal phases produced during digestion of a SNEDDS using the in vitro lipolysis model revealed the formation of similar structures as previously reported. The zeta-potential of the media was negatively charged and decreased from -23 to -35 mV with increasing surfactant/lipid load. Lower zeta-potential values (-16 mV) obtained for the structures formed during the lipid hydrolysis of the SNEDDS were probably due to the presence of calcium, which shields the surface, thereby reducing the charge.
Conclusions:
The diversity of these vesicles in terms of size, lamellarity, and internal organization advocate their important role during lipid digestion in the gastrointestinal milieu.

