Posted by Cyclodextrins (CDs) have long been pioneers in industries such as pharmaceuticals, food and cosmetics, and they continue to open up more and more fascinating new fields. This is because they offer many advantages as complexing agents, scaffolds, excipients, etc. However, they suffer from one major drawback: limited solubility in water especially for β-cyclodextrin. To unlock their full potential, improving their solubility is essential. The good news? Green solvents may hold the key to solving this challenge.
The problem: β-Cyclodextrin is the most widely used CD. However, it is only soluble at 18.5 grams per liter in water at 25 °C, limiting its broader use in many formulations.
Traditional Solutions: Over the years, researchers have tried several strategies such as salting in, hydrotropy, deprotonation/ionization and solvation to increase CD solubility. These strategies showed different enhancement factors. Salts alone were not very efficient, but their combination with organic hydrotropes such as urea, which itself was able to solubilize native CDs remarkably, increased the solvation capacity. Among acids, only citric acid and tartaric acid were effective in increasing the solubility of CDs. CDs are highly soluble and stable in highly basic solutions. However, the basicity of the medium may limit the range of applications. While these strategies provide some improvement, they often fall short, either because they interfere with the complexation phenomenon or because they don’t meet sustainability requirements.
The Green Solution: Green solvents such as ionic liquids (ILs) and deep eutectic solvents (DESs) are emerging as an interesting opportunity to address the problem of solubility of native CDs. Among the green solvents, DESs may be the most relevant. The solubility of β-CD can reach 1000 g/L at 20 ◦C in ChCl:urea (1:2) without any aggregation. In addition, DESs not only replace organic solvents but also overcome all the drawbacks of using synthetic ILs, especially their multistep synthesis, toxicity and environmental hazards. Thus, it seems that DESs could be considered in many cases to overcome the limitations of aqueous solubility of CDs. However, research is still in its infancy and many gaps remain to be filled.
Why it matters? The use of green solvents, specifically DESs, to improve CD solubility is more than just a technical advancement. It is a step towards sustainable innovation. By improving CD solubility in a greener way, industries can create green formulations with low environmental impact.
The future of cyclodextrins is green chemistry. Are you ready for sustainable innovation?
M. Kfoury, S. Fourmentin: State of the art in cyclodextrin solubility enhancement. Are green solvents the solution? J. Mol. Liquids, 410, 125599, 2024. https://doi.org/10.1016/j.molliq.2024.125599.