Design and processing of drug delivery formulations of therapeutic deep eutectic systems for tuberculosis

Unravelling the nature of citric acid:l-arginine:water mixtures: the bifunctional role of water

“…This scenario changes upon water addition. As reported by Santos et al and Roda et al, ternary mixtures of citric acid:L-arginine:water at certain compositions are liquid at room temperature 15,16 . In the present work, the SLE of these mixtures was studied ( Figure 5).…”

“…This is a non-regular solution effect. Interestingly, the mixtures of citric acid:L-arginine:water previously reported to be liquid (1:1:4, 1:1:5, 1:1:6, 1:1:7, 2:1:7, 2:1:8, 2:1:9 mol ratios 15,16 ) correspond to water molar contents between 0.7 and 0.8, which coincide within the range where this 'non-regular' behavior was detected. Moreover, the lowest  cit values predicted by the ePC-SAFT model and respective ratios, are in accordance with the formation of liquid phase mixtures at the ratios previously reported and herein explored.…”

“…While these studies are all based on choline chloride-based DES, they highlight the importance of characterizing the water influence on other DES, opening the possibility to include water in the DES preparation as a starting material rather than a solvent. Recently, mixtures of citric acid:L-arginine:water of mole ratios 1:1:4, 1:1:5, 1:1:6, 1:1:7, 2:1:7, 2:1:8, 2:1:9 were reported as new DES 15,16 , given their low water amounts, between 15 to 25 weight percent. Although the authors named these mixtures as DES, given the complexity of these systems and the presence of water, other possibilities may be considered.…”

Deep Eutectic Solvents and Pharmaceuticals

“…In the area of drug delivery, DES have been applied as novel solvents, as novel API formulations (API-DES) or as agents with specific activity that can fit the needs for the design of drug delivery systems in several routes of administration [89][90][91]. These mixtures have been conjugated with different polymers and biopolymers producing different drug delivery systems, such as hydrogels, particles and nanofibers, among others [90][91][92]. Figure 5 summarizes the DES' application in drug delivery systems and their function in the development of the systems and therapeutic action.…”

“…A more extensive study of DES has enabled different administration routes to be considered, as is the case of using these mixtures for nasal drug delivery [90,92]. The correct selection of DES based on properties such as melting temperature and viscosity can be an advantage when considering the drug delivery application.…”