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

Abstract

Deep eutectic solvents (DES) are products of interaction between solid parent compounds resulting in a liquid at room temperature due to significant melting point depression. Such phenomenon has been employed to improve drugs’ biopharmaceutical behavior by including at least one API as DES former to produce a therapeutic DES (THEDES). DES physicochemical characteristics are affected by those of the parent compounds. Investigating such relation can help in tailoring THEDES formation for specific outcomes. This was done by comparing THEDES of lidocaine with either of structurally similar ibuprofen or ketoprofen through thermalanalysis, FTIR and rheological studies to highlight the effect of different physicochemical properties on the formed THEDES. Eutectic composition for both products was similar, indicating the important role of supramolecular complementarity in eutectic point determination. Glass transition (Tg)of drugs seemed to have direct impact on Tg of the formed THEDES where higher Tg ketoprofen produced a higher Tg THEDES. Similarly, higher number of hydrogen bonding sites within ketoprofen structure led to more viscous and thermally stable product. Moreover, the degree of charge involvement in the interaction network was related to pKa of the drugs. Such findings can help to construct a structural based approach to select THEDES components.

Keywords

• deep eutectic solvent
• thedes
• melting point
• physicochemical characters