Amorphous Solid Dispersion of Niclosamide with Water‐Soluble β‐Cyclodextrins for Dissolution and Bioavailability Enhancement

Abstract

AbstractCyclodextrins (CDs) are cyclic oligosaccharides widely employed for the solubility enhancement of poorly water‐soluble drugs. Niclosamide is a BCS class II drug for tapeworm infections and is currently under repurposing for various other indications, including COVID‐19. Due to its low aqueous solubility, a high daily dose (2 g) is required for clinical efficacy. Herein, we investigate the potential of beta‐cyclodextrin (β‐CD) and its sulfobutylether and hydroxypropyl derivatives for the dissolution enhancement of niclosamide. The solid dispersions were prepared by kneading the drug and cyclodextrins together by adding solvent, water: methanol (1 : 1 v/v). Among various CDs studied, 2‐Hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) in the 1: 2 molar ratio (SB‐IC‐N4 batch) shows the most significant improvement in water solubility of niclosamide (6.3 vs. 182 μg/ml), resulting in 2‐fold improved in‐vitro dissolution. The comparative oral pharmacokinetics in Wistar rats at 50 mg/kg produced 1.69‐fold higher plasma exposure of niclosamide. The spectral characterization provided molecular insights into interactions of niclosamide with HP‐β‐CD. These results suggest that the dispersion of niclosamide with HP‐β‐CD aid in faster dissolution and better drug bioavailability.