Enhancement of Solubility and Bioactivity of Zonisamide Through Supramolecular Inclusion With β-Cyclodextrin: A Comprehensive Analytical and Computational Study

Abstract

This study delved into the interaction between the neurological drug zonisamide (ZNS) and β-cyclodextrin (β-CD) using an innovative coprecipitation technique, leading to the formation of a stable 1:1 supramolecular inclusion complex (IC). Analytical tools, including ¹H NMR, FTIR spectroscopy, ESIMS, UV–vis spectroscopy, and SEM, revealed the structural details of this assembly. Job's plot confirmed the stoichiometric ratio, whereas binding constants were determined through UV–vis spectroscopic titrations using the Benesi–Hildebrand method. ESIMS data corroborated these findings. Molecular modeling and density functional theory (DFT) calculations provided additional evidence of complexation, demonstrating the stability of the IC through adsorption energy analysis. Biological evaluations showed enhanced antioxidant and antimicrobial activities of the ZNS+β-CD complex compared to pure ZNS, reflecting its improved properties. Encapsulation within β-CD significantly increased the solubility of ZNS in aqueous media, enabling lower effective dosages and reducing potential side effects. The study's experimental and computational findings aligned seamlessly, affirming the encapsulation of ZNS within β-CD and advancing our understanding of supramolecular chemistry. This work highlights the potential of β-CD to optimize drug solubility and therapeutic efficiency, offering a promising approach for improved drug delivery systems.