Self-emulsifying drug delivery systems: About the fate of hydrophobic ion pairs on a phospholipid bilayer

Purpose

To investigate the fate of hydrophobic ion pairs (HIPs) and self-emulsifying drug delivery systems (SEDDS) containing HIPs on a phospholipid bilayer.

Methods

HIPs of fluorescein (FL) were formed using the lipophilic cationic counter ion octadecylamine (OCT). HIPs were incorporated into SEDDS comprising 30% Capryol 90, 40% Cremophor RH, 20% Maisine 35-1 and 10% propylene glycol and evaluated regarding log D_{SEDDS/release medium} and dissociation of these complexes at various pH values over time. Furthermore, in vitro permeation studies were carried out in order to evaluate the fate of HIPs and SEDDS containing HIPs on a phospholipid bilayer.

Results

HIPs of FL with OCT showed the highest precipitation efficiency at a stoichiometric ratio of 1:1. HIPs (1% v/v) were incorporated into SEDDS pre-concentrate. Log D_{SEDDS/release medium} of incorporated complexes was between 2.5 and 3.5. HIPs dissociated in aqueous media up to 20% at pH 6–7.4 within 4 h. In vitro permeation studies revealed 2.7-fold improved permeation of FL after complex formation and incorporation in SEDDS. Results suggest that SEDDS fuse with the phospholipid bilayer facilitating the permeation of incorporated HIPs.

Conclusion

SEDDS enhance the stability of incorporated HIPs and improve their permeation across phospholipid bilayers.

Highlights

• Enhancement in the lipophilicity of hydrophilic anionic model drug fluorescein via hydrophobic ion pairing.

• Incorporation of hydrophobic ion pairs (HIPs) in to lipid-based formulation.

• Assessment of Caco-2 cells viability via resazurin assay.

• The fate of HIPs and lipid-based formulation during permeation across the lipophilic membrane was evaluated.