The counter ion: Expanding excipient functionality

Abstract

It is increasingly evident that drug delivery mechanisms involving an assembly of molecules, or changes in their conformation, are often counter ion dependent, and may therefore be conveniently modulated by counter ion selection. Such mechanisms include supramolecular assembly, topological changes or ion pair formation to penetrate cell membranes and improve transfection efficiency, self association to achieve ratiometric release and interfacial force manipulation, and salt bridge engineering for spatial and temporal control of drug delivery. Counter ions serve as useful tools in pharmaceutical manufacturing processes, such as, imparting enantioselectivity, enhancing conventional and biocatalytic reaction rates, controlling the precipitant product's physico-chemical characteristics (such as morphology, particle size and surface area), imparting conductivity to polymers, in the bottom up synthesis of nano and micro electromechanical devices, enhancing protein refolding yields, and as selectable components of ionic liquids. When combined with other 'carrier system' approaches, counter ion modulation has the potential to significantly improve drug targeting and delivery. Our failure to recognize and understand its utility, coupled with a historically dismissive weltanschauung, has so far prevented us from unlocking its full potential. © IPEC-Americas Inc.