Preparation and Characterization of Liquisolid Systems of Citrus Bioflavonoid Extract for Enhancing Hesperidin Release

Abstract

Citrus bioflavonoids, especially hesperidin, have garnered interest for their pharmacological attributes. The clinical applicability of hesperidin is constrained by its limited absorption. This study aimed to prepare and characterize liquisolid systems of citrus bioflavonoid extract (CBE) to enhance hesperidin release. Solubility investigations revealed that N-methyl-2-pyrrolidone (NMP) with 1–3% sodium dodecyl sulfate (SDS) yielded the greatest solubility (25% w/w) of hesperidin. Six CBE liquisolid (CBE-LS) formulations were successfully fabricated with CBE concentrations in NMP-based liquid medicaments of 10–25%, with or without SDS. All CBE-LS formulations exhibited acceptable flowability and content uniformity. FTIR data suggested potential intermolecular associations between CBE and 1%SDS-NMP-based CBE-LS. PXRD demonstrated a complete transformation to a non-crystalline state of CBE exclusively in CBE-LS formulated with 10–15% CBE concentrations. CBE-LS improved the release efficiency of hesperidin by 2.5–3.8-fold. CBE-LS exhibited relatively low cytotoxicity to Caco-2 cells. Tablets of CBE-LS (CBE-LST) based on 20% CBE in 1% SDS-NMP systems were successfully produced, exhibiting satisfactory tablet characteristics, content consistency, and enhanced release efficiency. CBE-LST exhibited no marked physical changes over three months upon storage, but the percentage of remaining hesperidin was significantly affected by storage temperature. This study highlights the potential of liquisolid systems as a useful approach for enhancing the release of oral formulations containing hesperidin and CBE.