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

• Published in: Journal of molecular liquids Vol. 312; p. 113382
• Main Authors: Nazir, Imran, Ghezzi, Martina, Asim, Mulazim Hussain, Phan, Thi Nhu Quynh, Bernkop-Schnürch, Andreas
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15.08.2020
• Subjects: Hydrophobic ion pairing (HIP); Lipid based drug delivery; Mucosal drug delivery; Permeation enhancement; Phospholipid bilayer; Self-emulsifying drug delivery systems (SEDDS); Permeation enhancement; Hydrophobic ion pairing (HIP); Self-emulsifying drug delivery systems (SEDDS); Mucosal drug delivery; Lipid based drug delivery; Phospholipid bilayer
• ISSN: 0167-7322; 1873-3166
• DOI: 10.1016/j.molliq.2020.113382

To investigate the fate of hydrophobic ion pairs (HIPs) and self-emulsifying drug delivery systems (SEDDS) containing HIPs on a phospholipid bilayer. 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 DSEDDS/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. 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 DSEDDS/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. SEDDS enhance the stability of incorporated HIPs and improve their permeation across phospholipid bilayers. [Display omitted] •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.