Nebulised Isotonic Hydroxychloroquine Aerosols for Potential Treatment of COVID-19
The coronavirus disease 2019 (COVID-19) is an unprecedented pandemic that has severely impacted global public health and the economy. Hydroxychloroquine administered orally to COVID-19 patients was ineffective, but its antiviral and anti-inflammatory actions were observed in vitro. The lack of effic...
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doaj-d631ef303f354497a635f67b29b38b972021-08-26T14:13:14ZengMDPI AGPharmaceutics1999-49232021-08-01131260126010.3390/pharmaceutics13081260Nebulised Isotonic Hydroxychloroquine Aerosols for Potential Treatment of COVID-19Waiting Tai0Michael Yee Tak Chow1Rachel Yoon Kyung Chang2Patricia Tang3Igor Gonda4Robert B. MacArthur5Hak-Kim Chan6Philip Chi Lip Kwok7Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, AustraliaAdvanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, AustraliaAdvanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, AustraliaAdvanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, AustraliaPulmoquine Therapeutics, Inc., 1155 Camino Del Mar Suite 481, Del Mar, CA 92014, USAPulmoquine Therapeutics, Inc., 1155 Camino Del Mar Suite 481, Del Mar, CA 92014, USAAdvanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, AustraliaAdvanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, AustraliaThe coronavirus disease 2019 (COVID-19) is an unprecedented pandemic that has severely impacted global public health and the economy. Hydroxychloroquine administered orally to COVID-19 patients was ineffective, but its antiviral and anti-inflammatory actions were observed in vitro. The lack of efficacy in vivo could be due to the inefficiency of the oral route in attaining high drug concentration in the lungs. Delivering hydroxychloroquine by inhalation may be a promising alternative for direct targeting with minimal systemic exposure. This paper reports on the characterisation of isotonic, pH-neutral hydroxychloroquine sulphate (HCQS) solutions for nebulisation for COVID-19. They can be prepared, sterilised, and nebulised for testing as an investigational new drug for treating this infection. The 20, 50, and 100 mg/mL HCQS solutions were stable for at least 15 days without refrigeration when stored in darkness. They were atomised from Aerogen Solo Ultra vibrating mesh nebulisers (1 mL of each of the three concentrations and, in addition, 1.5 mL of 100 mg/mL) to form droplets having a median volumetric diameter of 4.3–5.2 µm, with about 50–60% of the aerosol by volume < 5 µm. The aerosol droplet size decreased (from 4.95 to 4.34 µm) with increasing drug concentration (from 20 to 100 mg/mL). As the drug concentration and liquid volume increased, the nebulisation duration increased from 3 to 11 min. The emitted doses ranged from 9.1 to 75.9 mg, depending on the concentration and volume nebulised. The HCQS solutions appear suitable for preclinical and clinical studies for potential COVID-19 treatment.https://www.mdpi.com/1999-4923/13/8/1260hydroxychloroquinecoronavirus disease 2019 (COVID-19)vibrating mesh nebuliserinhalationaerosoldroplet |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Waiting Tai Michael Yee Tak Chow Rachel Yoon Kyung Chang Patricia Tang Igor Gonda Robert B. MacArthur Hak-Kim Chan Philip Chi Lip Kwok |
spellingShingle |
Waiting Tai Michael Yee Tak Chow Rachel Yoon Kyung Chang Patricia Tang Igor Gonda Robert B. MacArthur Hak-Kim Chan Philip Chi Lip Kwok Nebulised Isotonic Hydroxychloroquine Aerosols for Potential Treatment of COVID-19 Pharmaceutics hydroxychloroquine coronavirus disease 2019 (COVID-19) vibrating mesh nebuliser inhalation aerosol droplet |
author_facet |
Waiting Tai Michael Yee Tak Chow Rachel Yoon Kyung Chang Patricia Tang Igor Gonda Robert B. MacArthur Hak-Kim Chan Philip Chi Lip Kwok |
author_sort |
Waiting Tai |
title |
Nebulised Isotonic Hydroxychloroquine Aerosols for Potential Treatment of COVID-19 |
title_short |
Nebulised Isotonic Hydroxychloroquine Aerosols for Potential Treatment of COVID-19 |
title_full |
Nebulised Isotonic Hydroxychloroquine Aerosols for Potential Treatment of COVID-19 |
title_fullStr |
Nebulised Isotonic Hydroxychloroquine Aerosols for Potential Treatment of COVID-19 |
title_full_unstemmed |
Nebulised Isotonic Hydroxychloroquine Aerosols for Potential Treatment of COVID-19 |
title_sort |
nebulised isotonic hydroxychloroquine aerosols for potential treatment of covid-19 |
publisher |
MDPI AG |
series |
Pharmaceutics |
issn |
1999-4923 |
publishDate |
2021-08-01 |
description |
The coronavirus disease 2019 (COVID-19) is an unprecedented pandemic that has severely impacted global public health and the economy. Hydroxychloroquine administered orally to COVID-19 patients was ineffective, but its antiviral and anti-inflammatory actions were observed in vitro. The lack of efficacy in vivo could be due to the inefficiency of the oral route in attaining high drug concentration in the lungs. Delivering hydroxychloroquine by inhalation may be a promising alternative for direct targeting with minimal systemic exposure. This paper reports on the characterisation of isotonic, pH-neutral hydroxychloroquine sulphate (HCQS) solutions for nebulisation for COVID-19. They can be prepared, sterilised, and nebulised for testing as an investigational new drug for treating this infection. The 20, 50, and 100 mg/mL HCQS solutions were stable for at least 15 days without refrigeration when stored in darkness. They were atomised from Aerogen Solo Ultra vibrating mesh nebulisers (1 mL of each of the three concentrations and, in addition, 1.5 mL of 100 mg/mL) to form droplets having a median volumetric diameter of 4.3–5.2 µm, with about 50–60% of the aerosol by volume < 5 µm. The aerosol droplet size decreased (from 4.95 to 4.34 µm) with increasing drug concentration (from 20 to 100 mg/mL). As the drug concentration and liquid volume increased, the nebulisation duration increased from 3 to 11 min. The emitted doses ranged from 9.1 to 75.9 mg, depending on the concentration and volume nebulised. The HCQS solutions appear suitable for preclinical and clinical studies for potential COVID-19 treatment. |
topic |
hydroxychloroquine coronavirus disease 2019 (COVID-19) vibrating mesh nebuliser inhalation aerosol droplet |
url |
https://www.mdpi.com/1999-4923/13/8/1260 |
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