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

• Published in: Pharmaceutical development and technology 2024-08, Vol.29 (7), p.1-702
• Main Authors: Elshaer, Mahmoud, Osman, Shaaban K, Mohammed, Ahmed M, Zayed, Gamal
• Format: Article
• Language: English
• ISSN: 1083-7450; 1097-9867; 1097-9867
• DOI: 10.1080/10837450.2024.2378498

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 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, studies are crucial to validate these promising results.