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

Abstract

This study aimed to examine the influence of 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 Classification 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 of EA was multiplied by 9.92 and 2.98 in the presence of 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 of EA inclusion complexes with βCD was partial. However, these results did not indicate the appearance of EA inclusion complexes with γCD. These relatively modest results in terms of increased EA solubility, obtained with 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.