Nebulised Isotonic Hydroxychloroquine Aerosols for Potential Treatment of COVID-19
Analysis of HCQ solutions suitable for nebulization for COVID-19.
Tai et al., 14 Aug 2021, peer-reviewed, 8 authors.
Nebulised Isotonic Hydroxychloroquine Aerosols for Potential
Treatment of COVID-19
Waiting Tai 1 , Michael Yee Tak Chow 1 , Rachel Yoon Kyung Chang 1 , Patricia Tang 1 , Igor Gonda 2 ,
Robert B. MacArthur 2 , Hak-Kim Chan 1 and Philip Chi Lip Kwok 1, *
Citation: Tai, W.; Chow, M.Y.T.;
Chang, R.Y.K.; Tang, P.; Gonda, I.;
MacArthur, R.B.; Chan, H.-K.;
Kwok, P.C.L. Nebulised Isotonic
Hydroxychloroquine Aerosols for
Potential Treatment of COVID-19.
Pharmaceutics 2021, 13, 1260. https://
Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health,
The University of Sydney, Camperdown, NSW 2006, Australia; firstname.lastname@example.org (W.T.);
email@example.com (M.Y.T.C.); firstname.lastname@example.org (R.Y.K.C.);
email@example.com (P.T.); firstname.lastname@example.org (H.-K.C.)
Pulmoquine Therapeutics, Inc., 1155 Camino Del Mar Suite 481, Del Mar, CA 92014, USA;
email@example.com (I.G.); firstname.lastname@example.org (R.B.M.)
Correspondence: email@example.com; Tel.: +61-2-8627-6456; Fax: +61-2-9351-4391
Abstract: The coronavirus disease 2019 (COVID-19) is an unprecedented pandemic that has severely
impacted global public health and the economy. Hydroxychloroquine administered orally to COVID19 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.
Academic Editor: Jason T. McConville
Received: 24 May 2021
Keywords: hydroxychloroquine; coronavirus disease 2019 (COVID-19); vibrating mesh nebuliser;
inhalation; aerosol; droplet
Accepted: 12 August 2021
Published: 14 August 2021
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