Crystalline vs. Ionic Liquid Salt Forms of Active Pharmaceutical Ingredients: A Position Paper

Abstract

Why not consider liquid salt forms of active pharmaceutical ingredients (APIs) as an alternative versatile tool in the pharmaceutical industry? Recent developments have shown that known APIs can be readily converted into ionic liquids and that these novel phases often possess different properties (e.g., improved solubilities and dissolution rates), which may have a direct impact on the pharmacokinetics and pharmacodynamics of the drug. They may also offer the potential of novel and more efficient delivery modes, as well as patent protection for each of the new forms of the drug. Since these pharmaceutically active ionic liquids represent a thermodynamically stable phase, they avoid the troublesome issues surrounding polymorphism and "polymorphic transformation." In some cases, an active cation and an active anion can be combined to produce a liquid possessing dual functionality. Here we examine and challenge the current industry reliance on crystalline APIs by discussing the breadth and potential impact of liquid salts as a possible approach to phase control.

Development of Novel Ionic Liquid-Based Microemulsion Formulation for Dermal Delivery of 5-Fluorouracil

“…Due to their outstanding properties including nonvolatility, high ionic conductivity, and recyclability, these are regarded as greener solvents in comparison to conventional organic solvents (1)(2)(3)(4). Moreover, recently, the possibilities of using ILs in pharmaceutical sciences have been investigated due to their modifiable physicochemical properties like viscosity and polarity, reaction media and catalytic role in active pharmaceutical ingredient (PI) synthesis, and, most importantly, the excellent solubilization ability for hydrophobic and hydrophilic drugs (5)(6)(7)(8)(9).…”

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.…”

“…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. Besides the elimination of polymorphism and the adjustable solubility, the question of how ionic liquids conjugated with pharmaceutical ingredients could enhance the transport across the membrane is of interest within the APIs context (Dean et al, 2009;Stoimenovski and MacFarlane, 2011;Stoimenovski et al, 2010;Variankaval et al, 2008).…”

Using UCST Ionic Liquid as a Draw Solute in Forward Osmosis to Treat High-Salinity Water

“…With these special properties, ILs have been widely used in many applications, such as batteries, 24,25 catalysis, [26][27][28] drug delivery 29,30 and solvents [31][32][33] . A recent patent described a FO process to use ILs as draw solutions, but didn't mention the regeneration methods.…”