Use of voltammetry for in vitro equilibrium and transport studies of ionisable drugs

Abstract

In this review, we will briefly outline the voltammetric investigations of the transfer of ionisable drugs at the interface between two immiscible electrolyte solutions. The voltammetric techniques enable the determination of some key in vitro properties of ionisable drugs, including partition coefficient, diffusioncoefficient and membrane permeability. Some successful applications will be highlighted, together with the background methodologies.

Oxygen Reduction at the Liquid–Liquid Interface: Bipolar Electrochemistry through Adsorbed Graphene Layers

“…[1] Interest in this area has grown rapidly since the 1970s, driven by potential applications such as sensing, nuclearw aste reclamation, nanoparticle assembly,m imicking biological membranes and predicting drug transport in vivo. [2][3][4] Over the last decade, the use of ITIES systemsf or reduction reactions has received ag reat deal of attention,w ith both the oxygen reduction and hydrogen evolution [28][29][30][31][32][33][34][35][36][37][38] reactions (ORR and HER, respectively) widely studied. [39][40][41] Equations (1)…”

“…Study of the interface between two immiscible electrolyte solutions (ITIES) has a long history, dating back to the first experiment by Nernst and Riesenfeld in 1902 . Interest in this area has grown rapidly since the 1970s, driven by potential applications such as sensing, nuclear waste reclamation, nanoparticle assembly, mimicking biological membranes and predicting drug transport in vivo . Over the last decade, the use of ITIES systems for reduction reactions has received a great deal of attention, with both the oxygen reduction and hydrogen evolution reactions (ORR and HER, respectively) widely studied …”

Applications of Electrochemistry at Liquid/Liquid Interfaces for Ionizable Drug Molecule Sensing

“…Thorough review articles on evaluating P of an ionizable drug experimentally using electrochemical techniques such as cyclic voltammetry, differential pulse voltammetry and square wave voltammetry can be found in the literature. 10,12,13) Such electrochemical lipophilicity investigations on drug ion transfer processes across the ITIES can provide an important insight for developing drug ion sensors. Nevertheless, only few reports are available for particularly ionizable drugs compared to the vast research efforts made on the use of ITIES for sensing of inorganic and also small organic ions.…”

“…The majority of ITIES studies on drug molecules have focused on understanding the lipophilicities of interest of drugs for pharmacokinetics via voltammetric investigations of differently charged drug species partitioned at a polarised ITIES. [9][10][11][12][13][14] Along with thermodynamic investigation of drugs at ITIES, these studies have provided important information and paved pathways for designing drug ion sensors. Therefore, this review will first introduce a short background of ion transfer reactions across a polarized ITIES followed by the construction of an interface between two immiscible electrolyte solutions, which is the foundation of sensing platform developments.…”

Voltammetric study of the partitioning of macrolide antibiotics at the water/nitrobenzene interface. Relationship to the pharmacokinetic profiling of macrolides

“…The interfaces nitrobenzene/water, as well as 1,2-dichloroethane/water are good models for biological membranes, since they enable the rapid and precise determination of the electrochemical properties of ionised biological molecules. Both interfaces have already been used to probe the transfer of ionic drug compounds [14][15][16][17][18].…”