The Impact of Sugar Moieties on the Solubility of Naringin-Neohesperidin Co-Amorphous Solid Dispersions

Background/Objectives: Co-amorphous solid dispersions (c-ASD) are a promising strategy for enhancing the dissolution of poorly water-soluble drugs. Naringin (NA) and neohesperidin (NE) are dihydroflavonoid components and are poorly soluble. They can form a c-ASD. Concerning the c-ASD formation mechanism, the intermolecular forces between the non-sugar aglycones of NA and NE have been determined; however, the roles of the sugar chains, which account for nearly 50% of the overall molecular weight of both compounds, are unclear. Therefore, the impact of the sugar moiety on the solubility of NA-NE c-ASD needs to be investigated. Methods: The sugar removal products of NA and NE are naringenin-7-O-glucoside, naringenin, hesperetin-7-O-glucoside, and hesperetin. Therefore, in this study, the solubility profiles of NA with hesperetin-7-O-glucoside and hesperetin, and of NE with naringenin-7-O-glucoside and naringenin were assessed by dissolution determination and analyzed by PXRD. Results: These results indicated that the rhamnose and glucose moieties on the NE sugar chain and the glucose moiety on the NA sugar chain are vital to the stability and solubility of NE-NA c-ASD. The rhamnose moiety on the sugar chain of NA is removable, without which a stable soluble aggregator may also be constructed, but the soluble aggregator formation ability is weakened. Conclusions: The results of this study not only inform the rational selection of co-formers for structurally similar flavanone glycosides but can also help chemists modify the c-ASD structure based on the sugar moiety.