The influence of hydroxypropyl-β-cyclodextrin on the solubility, dissolution, cytotoxicity, and binding of riluzole with human serum albumin.

Cyclodextrin-related host-guest encapsulation is fundamental to modulate the solubility of riluzole (RLZ), promoting its potential pharmaceutical applications. The supramolecular interaction of RLZ and hydroxypropyl-β-cyclodextrin (HP-β-CD) was examined through FT-IR spectroscopy, DSC-TGA, PXRD, (1)HNMR, 2D ROESY, ssNMR, and SEM. The HP-β-CD/RLZ inclusion complex was formed at a molar ratio of 1:1. The stability constant (K=2327 M(-1)) and the corresponding thermodynamic parameters were ascertained through phase solubility studies. The water solubility and dissolution rate of RLZ notably increased in the presence of HP-β-CD, whereas the inclusion complex did not increase the RLZ toxicity toward the LO2 cell line. The influence of HP-β-CD on RLZ-human serum albumin (HSA) binding was investigated via fluorescence spectroscopy. Fluorescence quenching of HSA by RLZ in the presence and absence of HP-β-CD were both static quenching. Data analysis showed that the addition of HP-β-CD weakened the quenching and binding of RLZ with HSA but did not affect the binding site and binding force between RLZ and HSA. Furthermore, molecular models were generated to determine the binding site between HSA and RLZ, and these models were consistent with the experimental data.