Estimating thermodynamic equilibrium solubility and solute-solvent interactions of niclosamide in eight mono-solvents at different temperatures.

Niclosamide is an FDA-approved oral anthelmintic drug currently being repurposed for COVID-19 infection. Its interesting applicability in multiple therapeutic indications has sparked interest in this drug/ scaffold. Despite its therapeutic use for several years, its detailed solubility information from Chemistry Manufacturing & Controls perspective is unavailable. Thus, the present study is intended to determine the mole fraction solubility of niclosamide in commonly used solvents and cosolvents at a temperature range of 298.15-323.15 K. The polymorphic changes from crystalline to monohydrate forms post-equilibration in various solvents were observed. The maximum mole fraction solubility of niclosamide at 323.15 K is 1.103 × 10-3 in PEG400, followed by PEG200 (5.272 × 10-4), 1-butanol (3.047 × 10-4), 2-propanol (2.42 × 10-4), ethanol (1.66 × 10-4), DMSO (1.52 × 10-4), methanol (7.78 × 10-5) and water (3.27 × 10-7). The molecular electrostatic potential showed a linear correlation with the solubility. PEG400 has higher electrostatic potential, and H-bond acceptor count, which forms a hydrogen bond with phenolic -OH of niclosamide and thus enhances its solubility. This data is valuable for the drug discovery and development teams working on the medicinal chemistry and process chemistry of this scaffold.

Techniques for analytical estimation of COVID-19 clinical candidate, niclosamide in pharmaceutical and biomedical samples.

Niclosamide is a well-known broad-spectrum antiparasitic drug used for human as well as veterinary tapeworm infections. Recently, it attracted attention as an antiviral agent for treating coronavirus disease 2019. It is administered orally in humans to treat tapeworm infections. Furthermore, it is a registered pesticide and molluscicide to control infections in the aquaculture industry. Its chronic environmental exposure has potential toxicities when such contaminated seafood is consumed. Therefore, monitoring its residual concentration in food products (seafood, water, water waste, etc.) and pharmaceuticals (active pharmaceutical ingredients, bulk drugs, and formulations) is imperative. The present review critically investigates the sophisticated techniques employed for analyzing niclosamide, its degradation products, and metabolites in various samples and matrices. The future scope for green analytical methods, green sample extraction and preparation is also deliberated.