Effect of alpha-cyclodextrin on drug distribution studied by electrochemistry at interfaces between immiscible electrolyte solutions.
The description and understanding of noncovalent interactions and distribution of potential new drug compounds in an organism is of paramount importance for the successful development of new drugs. In this work, a new procedure based on electrochemistry at the interface between two immiscible electrolyte solutions (ITIES) for addressing and discriminating between drug compound/ligand interactions in aqueous solution and nonspecific ligand effects on oil-water distribution behavior has been developed. The procedure is demonstrated using five drug compounds with different physical chemical parameters and alpha-cyclodextrin as the aqueous phase ligand. Alpha-cyclodextrin was chosen as an aqueous phase ligand, as it is frequently used in drug formulations to enhance solubility and bioavailability of drug compounds. Supplementary capillary electrophoresis experiments provided more detailed information on alpha-cyclodextrin drug complexation and, in combination with the electrochemical studies, provided information on solvation effects affecting the oil-water distribution of the drug compounds. The use of ligand shift ion partition diagrams for data presentation is a convenient format for the visualization of ligand effects on distribution behavior of related drug compounds.
Deryabina
Maria A
MA
Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Hansen
Steen H
SH
Østergaard
Jesper
J
Jensen
Henrik
H
D004563:Electrochemistry; D004573:Electrolytes / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012996:Solutions; D014867:Water / Q000737:chemistry; D047391:alpha-Cyclodextrins / Q000737:chemistry*
D004573:Electrolytes; D004364:Pharmaceutical Preparations; D012996:Solutions; D047391:alpha-Cyclodextrins; D014867:Water; C032613:alpha-cyclodextrin