Upgrading the topical delivery of poorly soluble drugs using ionic liquids as a versatile tool

Numerous studies are continuously being carried out in pursuit of formulations with higher performance. Problems such as poor drug solubility, which hinders drug incorporation into delivery systems and bioavailability, or limitations concerning the stability and performance of the formulations may cause difficulties, since solving all these drawbacks at once is a huge challenge. Ionic liquids (ILs), due to their tunable nature, may hypothetically be synthesized for a particular application. Therefore, predicting the impact of a particular combination of ions within an IL in drug delivery could be a useful strategy. Eight ILs, two choline amino acid ILs, two imidazole halogenated ILs, and four imidazole amino acid ILs, were prepared. Their applicability at non‐toxic concentrations, for improving solubility and the incorporation of the poorly soluble, ferulic, caffeic, and p‐coumaric acids, as well as rutin, into topical emulsions, was assessed. Next, the impact of the ILs on the performance of the formulations was investigated. Our study showed that choosing the appropriate IL leads to a clear upgrade of a topical emulsion, by optimizing multiple features of its performance, such as improving the delivery of poorly soluble drugs, altering the viscosity, which may lead to better sensorial features, and increasing the stability over time.