Ionic Liquids as Active Pharmaceutical Ingredients

Abstract

Ionic liquids (ILs) are ionic compounds that possess a melting temperature below 100 °C. Their physical and chemical properties are attractive for various applications. Several organic materials that are now classified as ionic liquids were described as far back as the mid-19th century. The search for new and different ILs has led to the progressive development and application of three generations of ILs: 1) The focus of the first generation was mainly on their unique intrinsic physical and chemical properties, such as density, viscosity, conductivity, solubility, and high thermal and chemical stability. 2) The second generation of ILs offered the potential to tune some of these physical and chemical properties, allowing the formation of "task-specific ionic liquids" which can have application as lubricants, energetic materials (in the case of selective separation and extraction processes), and as more environmentally friendly (greener) reaction solvents, among others. 3) The third and most recent generation of ILs involve active pharmaceutical ingredients (API), which are being used to produce ILs with biological activity. Herein we summarize recent developments in the area of third-generation ionic liquids that are being used as APIs, with a particular focus on efforts to overcome current hurdles encountered by APIs. We also offer some innovative solutions in new medical treatment and delivery options.

Evaluation of solubility and partition properties of ampicillin-based ionic liquids

“…Also, the use of an active drug in the liquid form (at room temperature) can avoid some of the issues of polymorphism associated with crystalline solids and, thus, dramatically influence the drug's solubility and dosages Ferraz et al, 2011;Stoimenovski et al, 2010). The use of this modular ionic liquids-based strategy to produce tuneable active pharmaceutical ingredients is very attractive since it allows infinite new possibilities, challenges and opportunities.…”

Permeation of Ionic Liquids through the skin

“…Neste âmbito, os líquidos iónicos (LI) têm sido estudados como promotores de solubilidade e permeação e têm sido desenvolvidos alguns estudos que utilizam estes materiais com esta finalidade [3,7,8]. Os LI são sais orgânicos [9,10], constituídos por iões, um catião orgânico e um anião orgânico ou inorgânico [9,11], que podem ser líquidos a temperaturas inferiores a 100 ºC [12,13] ou, em alguns casos, líquidos à temperatura ambiente [3,11]. Estes compostos têm diversas propriedades valiosas, sendo a suscetibilidade a modificações a mais relevante.…”

“…In this context, ionic liquids (ILs) have been studied as promoters of solubility and permeation and some studies have shown the use of these materials for this purpose [3,7,8,14,15]. Ionic liquids are organic salts [7,8], constituted by ions, an organic cation and an organic or inorganic anion [7,9], which are liquid at temperatures below 100 ºC [10,11] or, in some cases, liquids at room temperature [3,9]. These compounds have several valuable properties, the ease of modification being the most relevant.…”

Development of novel ionic liquids based on ampicillin

“…The use of an active drug in the liquid form (at room temperature) can avoid some of the issues of polymorphism associated with crystalline solids and, thus, dramatically influence the drug's solubility and dosages. 1,14,15 However, the entry of ILs into the biosciences has been delayed mainly because of the toxicity of the counterions.…”