Safer solvent use in the pharmaceutical industry

Ionic liquids

Ionic liquids are a fascinating category of solvents (Hallett and Welton, 2011). Most, maybe all the ionic compounds you will be familiar with are solids with very high melting points. Sodium chloride (table salt) has a melting point of 801 °C, and the psychiatric medicine lithium carbonate melts at 723 °C. Ionic organic compounds such as the food preservative sodium benzoate (melting point 410 °C) generally have lower melting points than inorganic substances but are still solids under most conditions. However, the combination of bulky cations and/or anions with delocalised charges can result in salts with a weak crystal lattice enthalpy and a propensity towards low melting points. An ionic liquid is typically defined as a salt with a melting point below 100 °C. The most common examples feature an asymmetrical imidazolium cation, but various other cations can also be used to form ionic liquids. Typical inorganic anions are tetrafluoroborate (BF4-) and hexafluorophosphate (PF6-), and bis(trifluoromethanesulfonyl) imide is also common. Triflate, carboxylate, and sulphate anions can also form ionic liquids.   

The synthesis of an ionic liquid from a bio-based feedstock is shown in the video below.

Use the tool below to try your own different cation-anion combinations and guess if the salt is an ionic liquid!

Ionic liquids were at the forefront of Green Chemistry, these curious compounds driving early interest in this new discipline. The lack of volatility exhibited by ionic liquids was seen as a solution to the negative consequences of conventional VOC solvents. However, industrial applications of ionic liquids have been limited. Some health and safety and environmental concerns have been raised (de Jesus and Filho, 2022), but this was inevitable given the innumerable permutations of cations and anions that exist. Cost and recovery have been a major barrier to the adoption of ionic liquids as well. But most contentious of all is the fact that organic solvents are typically needed to make ionic liquids, which means that the environmental impact of ionic liquids is not reduced, but actually increased compared to just using an organic solvent directly! Recycling of ionic liquids is a necessity to make them cost effective and justifiable based on their ‘greenness’.

Currently, ionic liquids are not solvents for pharmaceutical synthesis, at least not on a manufacturing scale, but there is interest in developing ionic liquid-based drug-delivery systems. In one example, anti-cancer chemotherapy drug Paclitaxel can be formulated for transdermal delivery (absorption through the skin) with an ionic liquid. This replaces intravenous injection which requires stabilising chemicals that can cause numerous side effects.