Factors governing the formation of THEDESs: A case study with propionic acid NSAIDs and lidocaine

Deep eutectic solvents (DES) are products of interaction betweensolid parent compounds resulting in a liquid at room temperature due to significantmelting point depression. Such phenomenon has been employed to improve drugs’ biopharmaceuticalbehavior by including at least one API as DES former to produce a therapeuticDES (THEDES). DES physicochemical characteristics are affected by those of the parentcompounds. Investigating such relation can help in tailoring THEDES formationfor specific outcomes. This was done by comparing THEDES of lidocaine witheither of structurally similar ibuprofen or ketoprofen through thermalanalysis, FTIR and rheological studies to highlight the effect of differentphysicochemical properties on the formed THEDES. Eutectic composition for bothproducts was similar, indicating the important role of supramolecularcomplementarity in eutectic point determination. Glass transition (Tg)of drugs seemed to have direct impact on Tg of the formed THEDESwhere higher Tg ketoprofen produced a higher Tg THEDES. Similarly,higher number of hydrogen bonding sites within ketoprofen structure led to moreviscous and thermally stable product. Moreover, the degree of chargeinvolvement in the interaction network was related to pKa of thedrugs. Such findings can help to construct a structural based approach to selectTHEDES components.