The influence of self-assembling supramolecular structures on the passive membrane transport of ion-paired molecules

Weak ion-ion interactions, such as those associated with ion-pair formation, are difficult to isolate and characterise in the liquid state, but they have the potential to alter significantly the physicochemical behaviour of molecules in solution. The aim of this work was to gain a better understanding of how ion-ion interactions influenced passive membrane transport. The test system was composed of propylene (PG) glycol, water and diclofenac diethylamine (DDEA). Infrared spectroscopy was employed to determine the nature of the DDEA ion-pair interactions and the drug-vehicle association. Passive transport was assessed using homogeneous synthetic membranes. Solution-state analysis demonstrated that the ion-pair was unperturbed by vehicle composition changes, but the solvent-DDEA interactions were modified. DDEA-PG/water hydrogen bonding influenced the ion-pair solubility (X-dev) and the solvent interactions slowed transport rate in PG-rich vehicles (0.84 +/- 0.05 mu g cm(-2) h(-1), at ln(X-dev) = 0.57). In water-rich co-solvents, the presence of strong water structuring facilitated a significant increase (p < 0.05) in transmembrane penetration rate (e.g. 4.33 +/- 0.92 mu g cm(-2) h(-1), at ln(X-dev) = -0.13). The data demonstrates that weak ion-ion interactions can result in the embedding of polar entities within a stable solvent complex and spontaneous supramolecular assembly should be considered when interpreting transmembrane transport processes of ionic molecules. (C) 2012 Elsevier B.V. All rights reserved.