Potential of Native Cyclodextrins and L-Lysine for Enhancing Ellagic Acid Aqueous Solubility

This study aimed to examine the inuence o β cyclodextrin (βCD) and γ cyclodextrin (γCD) alone and in combination with
L-lysine on ellagic acid (EA) solubility. Indeed, complexation with cyclodextrins can be used to improving the solubility of
drugs poorly soluble in water such as EA. EA is a Biopharamceutical Classication System (BCS) IV bioactive polyphenol
with numerous therapeutic activities, including antimalarial activities. However, its unfavorable physicochemical properties
limit its therapeutic use. Therefore, after a phase solubility study, we successfully prepared EA-βCD and γ CD binary solid
complexes using the freeze-drying technique. Methods including proton nuclear magnetic resonance (1H-NMR) analysis and
fourier-transform infrared (FTIR) spectroscopy were used to characterize the inclusion behaviors of the complexes of EA
with cyclodextrins both in solution and solid forms. The results of the phase solubility study indicated Ap-type diagrams of
EA with the two cyclodextrins (CDs). The solubility o EA was multiplied by 9.92 and 2.98 in the presence o γCD and βCD
respectively. Moreover, the complexes characterization by FTIR spectroscopy revealed the involvement of the C=O and EA
OH groups in the interaction with the CDs. The results of NMR spectroscopic characterization revealed that the formation
o EA inclusion complexes with βCD was partial. However, these results did not indicate the appearance o EA inclusion
complexeswith γCD. These relativelymodest results in terms of increased EAsolubility, obtainedwith cyclodextrins, prompted
us to use a third compound, l-lysine, to enhance CDs complexation. Thus, the formation of ternary complexes led to a very
significant increase EA solubility. Indeed, the incorporation of EA into EA-L-lysine-βCD and γ CD complexes increased its
water solubility at pH 7.4 by a factor of 555 and 663, respectively.