Experimental determination and correlation of naproxen solubility in biodegradable low-toxic betaine-based deep eutectic solvents and water mixtures at 293.15 K to 313.15 K

Abstract

For enhancement the low bioavailability of poorly water-soluble naproxen, three deep eutectic solvents (DESs) obtained from betaine as a hydrogen bond acceptor and propylene glycol, ethylene glycol or glycerol as a hydrogen bond donor (Bet/PG, Bet/EG or Bet/Gly DESs) are utilized from 0.0 to 1.0 mass fractions of DESs at T = (293.15–313.15) K under atmospheric pressure (≈ 85 kPa). The solubility values tend to enhance with enhancing mass fraction of each DES as well as increasing temperature and the maximum values are obtained in the highest mass fraction of DESs at 313.15 K. Besides, the Hansen solubility parameters are used to predict the selection of appropriate cosolvent system; the results indicated that the Bet/PG DES is a proper cosolvent for naproxen solubilization. Moreover, the equilibrated solid phase crystal of naproxen with neat solvents is characterized with X-ray powder diffraction analysis to identify no polymorphic transformation, solvate formation or crystal transition during the whole solvent crystallization process. In addition, the experimental solubilities are correlated with the temperature dependency of traditional cosolvency models including Jouyban-Acree, Jouyban-Acree-van't Hoff and modified Wilson-van't Hoff together with the activity coefficient models of NRTL, Wilson and UNIQUAC. The accuracies of the calculated solubilities are evaluated by calculation of the mean relative deviation (MRD%) and the results suggested that the Jouyban-Acree (MRD% ≤ 8.9) along with the NRTL activity coefficient model (MRD% ≤ 2.0) are more accurate than the others. Finally, the respective apparent thermodynamic quantities of the dissolution and mixing processes, namely Gibb's energy, enthalpy, and entropy are calculated based on the van't Hoff and Gibbs equations.