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bioRxiv · 10.1101/2021.08.16.456531

The pH Dependence of Niclosamide Solubility, Dissolution and Morphology Motivates a Potentially More Bioavailable Mucin-Penetrating Nasal and Throat Spray for COVID19, it's Contagious Variants, and Other Respiratory Viral Infections

Needham, D.
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Abstract

MotivationWith the coronavirus pandemic still raging, prophylactic nasal and early treatment throat sprays could help prevent infection and reduce viral load. Niclosamide has the potential to treat a broad range of viral infections if local bioavailability is optimized as mucin-penetrating solutions as opposed to more traditional microparticle-based sprays that cannot penetrate the mucin. ExperimentalpH-dependence of supernatant concentrations and dissolution rates of niclosamide were measured in buffered solutions by Nanodrop-UV/Vis-spectroscopy for niclosamide from different suppliers, as precipitated material, and as cosolvates. Data was compared to predictions from Henderson Hasselbalch and precipitation pH models. Optimal microscopy was used to observe the morphologies of precipitated and converted niclosamide. ResultsSupernatant-concentrations of niclosamide increased with increasing pH, from 1.77uM at pH 3.66 to 30uM at pH 8, and more rapidly from 90uM at pH8.5 to 300uM at pH 9.1, reaching 641uM at pH 9.5. Logarithmic rates for dissolution increased by [~]3x for pHs 8.62 to 9.44. However, when precipitated from supersaturated solution, niclosamide equilibrated to much lower final supernatant concentrations, reflective of more stable polymorphs at each pH that were also apparent for niclosamide from other suppliers and cosolvates. ConclusionsGiven niclosamides activity against COVID19, its more contagious variants, and other respiratory viral infections, these niclosamide solutions, that put the virus in lockdown, could represent universal prophylactic nasal and early treatment throat sprays. As solutions they would be the simplest and potentially most effective formulations from both an efficacy standpoint as well as manufacturing and distribution, with no cold chain. They now just need testing.

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Needham, D.. 2021-08-17. The pH Dependence of Niclosamide Solubility, Dissolution and Morphology Motivates a Potentially More Bioavailable Mucin-Penetrating Nasal and Throat Spray for COVID19, it's Contagious Variants, and Other Respiratory Viral Infections. https://doi.org/10.1101/2021.08.16.456531

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