Co-crystallization of Hesperidin with different co-formers to enhance solubility, antioxidant and anti-inflammatory activities

Abstract

Hesperidin (HSP) is a natural flavonoid glycoside with very low aqueous solubility and a slow dissolution rate, limiting its effectiveness. This study aims to address these issues by creating co-crystals of hesperidin with water-soluble small molecules (co-formers) such as L-arginine, glutathione, glycine, and nicotinamide. Using the solvent drop grinding method, we prepared three different molar ratios of hesperidin to co-formers (1:1, 1:3, and 1:5) and conducted in-vitro solubility and dissolution studies. The results demonstrated that the prepared co-crystals exhibited significantly enhanced solubility and dissolution rates compared to untreated hesperidin. Of particular note, the HSP co-crystals formula (HSP: L-arg 1:5) displayed approximately 4.5 times higher dissolution than pure hesperidin. Further analysis using FTIR, powder x-ray diffraction patterns, and DSC thermograms validated the formation of co-crystals between HSP and L-arginine. Additionally, co-crystallization with L-arginine improved the in vitro anti-inflammatory and antioxidant activities of hesperidin compared to the untreated drug. This study highlights the potential of using water-soluble small molecules (co-formers) through co-crystallization to enhance the solubility, dissolution, and biological activities of poorly water-soluble drugs. Furthermore, in vivo studies are crucial to validate these promising results.

Keywords:

• Hesperidin
• solubility
• co-crystallization
• SDG method
• in vitro anti-inflammatory and antioxidant study

Authors’ contributions

Mahmoud Elshaer: Conceptualization, methodology, software, statistical analysis, data interpretation, writing and editing. Shaaban K. Osman: Supervision. Ahmed M. Mohammed: Supervision and review. Gamal Zayed: Conceptualization, supervision, review, and editing.

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.