The Effect of N-Alkyl Substituents on the Usability of Imidazolium Cation-Based Ionic Liquids in Microemulsion Systems: A Technical Note

Abstract

Ionic liquids (ILs) are predominantly hailed as green solvents, due to their non-volatile, recyclable and non-hazardous nature. Their wide-spectrum applications can be implemented into conventional fields like lubricants, battery electrolytes and synthetic reaction media as well as newer arenas including supramolecular chemistry, separation techniques, and nuclear fuel reprocessing (1–4). However, due to their tunable physicochemical properties, some recent reports have suggested novel pharmaceutical uses of ionic liquids, including their use as active pharmaceutical ingredient salts (5), antimicrobials (6), solubilizers (7), and drug delivery systems (8,9). ILs are known to enhance the solubility profile of poorly water-soluble drugs (7,10). Therefore, the use of IL-based drug carrier systems could be a rational approach for delivery of insoluble drugs. Microemulsions are thermodynamically stable, isotropic systems composed of a polar phase (usually water), a nonpolar phase (oils) and amphiphilic phase (surfactant or mixture of surfactants). These systems provide numerous advantages over conventional drug delivery vehicles including nanometer sized aggregations, long-term stability, biocompatibility, easy preparation, and high solubilization tendency (11). Nevertheless, drug delivery using microemulsions is yet to fully attain its true potential, considering that only type and content of oils and surfactants have been customized, in general, by formulators to achieve different desirable characteristics. Little efforts have been performed in the direction of modifying the polar phase of microemulsion systems. We attempted to use ILs as alternative polar dispersed phase (in place of water) in the microemulsion systems. Moniruzzaman et al., recently have prepared the IL-based microemulsion carrier for drug delivery of poorly hydrophilic drugs (12). The report describes the use of dimethylimidazolium dimethylphosphate for successful transdermal delivery of poorly soluble drugs. However, to the best of our knowledge, we are for the first time reporting the screening of room temperature ionic liquids from two different series of 1- and 3-alkyl substituted imidazolium bromides to be used as components of microemulsion vehicles. The current study explains the synthesis of some imidazolium cation-based ILs with varying carbon chain length. Also, preliminary in vivo toxicity of these compounds was assessed by hemolysis assay using human blood to establish the possibility of using the ILs safely, and investigating relationship between N-alkyl substituents and their toxicity. Further, their effect on the microemulsion phase behavior was studied by constructing their pseudoternary phase diagrams using isopropyl myristate (IPM) as oil phase and Span 80 and Tween 80 mixture as emulgent phase. Model microemulsion systems consisting of the above mentioned ingredients were prepared and characterized.