Development of β‐Cyclodextrin‐Based Nanofiber Inclusion Complexes for Enhanced Solubility and Controlled Release of Nitazoxanide

Abstract Nitazoxanide (NTZ), a well‐established antiparasitic drug, has a wide range of antiviral activity. However, it faces challenges such as poor water solubility (0.00755 mg mL −1 ), limited bioavailability (1%), constrained permeability, and low thermal stability. This study aimed to enhance the properties and in vitro release of NTZ by inclusion complex (ICs)‐based nanofibers (NFs) through electrospinning under optimal conditions. Methyl‐β‐cyclodextrin (MCD) and sulfobutyl ether‐β‐cyclodextrin (SCD) acted as host molecules, aiding in the formation of ICs and electrospinning solutions, which led to the fabrication of NFs labeled MCD:NTZ and SCD:NTZ. The binding constant (K) values determined for the ICs were 56.12 and 73.46 M 1 for MCD:NTZ and SCD:NTZ using the Benesi–Hildebrand (B–H) plot via UV–visible spectroscopy. The findings indicate that the ICs of SCD:NTZ, which contains a sulfoxide group, form a more stable complex than that of MCD:NTZ. Additionally, our molecular docking analysis produced comparable findings, with the interaction of the thiazole ring within the CDs cavities showing a more stable conformation. The SEM analysis exhibited uniform, bead‐free, and smooth surface morphology, with the smallest diameters recorded as 225 ± 89, 260 ± 54, 72 ± 40, and 55 ± 27 nm for the MCD, SCD, MCD:NTZ, and SCD:NTZ NFs, respectively. Moreover, the solubility and thermal stability of NTZ were enhanced during the formation of MCD:NTZ and SCD:NTZ NFs, as evidenced by phase solubility and TGA analyses. The study on the release of NTZ in aqueous solution elucidates that the SCD:NTZ complex exhibited a higher release percentage (94.8 ± 1.94%) than the NFs of MCD:NTZ (86.2 ± 2.12%) and pristine NTZ (38.5 ± 1.81%). In summary, enhancing a drug's solubility, stability, and permeability is often regarded as an ideal pharmaceutical agent for oral drug delivery systems.