Excipient counterion dependent mechanisms in Pharmaceutical Development: a review

It is increasingly becoming evident that drug delivery mechanisms that involve 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; from imparting enantioselectivity, enhancing conventional and biocatalytic reaction rates, controlling the precipitant produt'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' centric approaches, counter ion modulation has the potential to significantly improve drug targeting and delivery. Inability to recognize and understand its utility, coupled with a historically dismissive weltanschauung, have so far underscored the ability to unlock its full potential.