Advances Brought by Hydrophilic Ionic Liquids in Fields Involving Pharmaceuticals

Abstract

The negligible volatility and high tunable nature of ionic liquids (ILs) have been the main drivers of their investigation in a wide diversity of fields, among which is their application in areas involving pharmaceuticals. Although most literature dealing with ILs is still majorly devoted to hydrophobic ILs, evidence on the potential of hydrophilic ILs have been increasingly provided in the past decade, viz., ILs with improved therapeutic efficiency and bioavailability, ILs with the ability to increase drugs' aqueous solubility, ILs with enhanced extraction performance for pharmaceuticals when employed in biphasic systems and other techniques, and ILs displaying low eco/cyto/toxicity and beneficial biological activities. Given their relevance, it is here overviewed the applications of hydrophilic ILs in fields involving pharmaceuticals, particularly focusing on achievements and advances witnessed during the last decade. The application of hydrophilic ILs within fields involving pharmaceuticals is here critically discussed according to four categories: (i) to improve pharmaceuticals solubility, envisioning improved bioavailability; (ii) as IL-based drug delivery systems; (iii) as pretreatment techniques to improve analytical methods performance dealing with pharmaceuticals, and (iv) in the recovery and purification of pharmaceuticals using IL-based systems. Key factors in the selection of appropriate ILs are identified. Insights and perspectives to bring renewed and effective solutions involving ILs able to compete with current commercial technologies are finally provided.

Progress in the applications of biocompatible ionic liquids: renewable commodity production, catalytic and pharmaceutical approaches – a review

“…Likewise, they are used as pretreatment to improve the performance of analytical methods and assist in the recovery and purification of pharmaceutical products. 133 Sagitha et al 134 developed a choline ester-based, dual-purpose IL with chloride as the anion ([Ch]IL) for stabilizing nucleic acids (DNA) and enhancing cellular drug uptake. [Ch]IL improved the cellular uptake of doxorubicin by increasing its water solubility.…”

Ionic Liquids: New Forms of Active Pharmaceutical Ingredients with Unique, Tunable Properties

“…Many API-ILs are prepared by solution metathesis, − which is often performed with the hydrochloride precursor of the cation and the alkali or silver salt of the acid in an appropriate VOCs (acetone or ethanol) to allow precipitation of byproduct NaCl or AgCl, that must be removed. Purification techniques developed for API ILs can reduce the remaining metal and halide content to ≤0.01% impurities.…”

Ionic Liquids: Momentous Tools in Transdermal Delivery of Biomacromolecules

“…Therefore, it is necessary to select asymmetric anions and cations as constituents of ILs. [88] Presently, choline and hydrocarbyl carboxylic acid, [89] choline and alkenoic acid, [38,85] and choline and fatty acid [42,90] Figure 1. A) Biological barriers that ionic liquids (ILs) need to overcome to deliver biomacromolecules transdermally: Stratum corneum, stratum granulosum, stratum spinosum, stratum basale, and other barriers.…”

“…Therefore, it is necessary to select asymmetric anions and cations as constituents of ILs. [ 88 ] Presently, choline and hydrocarbyl carboxylic acid, [ 89 ] choline and alkenoic acid, [ 38,85 ] and choline and fatty acid [ 42,90 ] have been studied and have exhibited good efficacy for transdermal delivery. Combining ILs with biomacromolecular drugs is a promising strategy of overcoming the SC barrier, however, the underlying mechanism by which ILs promote the penetration of biomacromolecule drugs through the SC barrier remains unexplored.…”