Inhalable Hydroxychloroquine Powders for Potential Treatment of COVID-19.
J Aerosol Med Pulm Drug Deliv
; 34(1): 20-31, 2021 02.
Article
in English
| MEDLINE | ID: covidwho-1066217
ABSTRACT
Background:
Hydroxychloroquine (HCQ) is one of the repurposed drugs proposed for the treatment of coronavirus disease 2019 (COVID-19). However, all the published clinical trials involve oral administration of the drug, although the disease is primarily a respiratory one. Direct inhaled delivery could reduce the side effects associated with oral use and ensure a high concentration of the drug in the lungs. In this study, inhalable HCQ powders were prepared and characterized for potential COVID-19 therapy.Methods:
Hydroxychloroquine sulfate (HCQ-sul) was jet milled (JM) followed by conditioning by storage at different relative humidities (43%, 53%, 58%, and 75% RHs) for 7 days. The solid-state properties, including particle morphology and size distribution, crystallinity, and vapor moisture profiles of HCQ-sul samples, were characterized by scanning electron microscopy, laser diffraction, X-ray powder diffraction, differential scanning calorimetry, thermogravimetric analysis, and dynamic water vapor sorption. The aerosol performance of the HCQ-sul powders was assessed using a medium-high resistance Osmohaler coupling to a next-generation impactor (NGI) at a flow rate of 60 L/min.Results:
The jet-milled powder showed a volume median diameter of 1.7 µm (span 1.5) and retained the same crystalline form as the raw HCQ-sul. A small amount of amorphous materials was present in the jet-milled HCQ-sul, which was convertible to the stable, crystalline state after conditioning at 53%, 58%, and 75% RH. The recovered fine particle fraction (FPF)recovered and the emitted fine particle fraction (FPFemitted) of the HCQ-sul sample immediately after jet milling and the samples after conditioning at 43%, 53%, and 58% RH were similar at â¼43% and 61%, respectively. In contrast, the sample having conditioned at 75%RH showed lower corresponding values at 33% and 26% respectively, due to the formation of solid bridges caused by excessive moisture.Conclusion:
Inhalable crystalline powders of HCQ-sul were successfully prepared, which can be used for clinical testing as a potential inhaled COVID-19 treatment.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
SARS-CoV-2
/
COVID-19 Drug Treatment
/
Hydroxychloroquine
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
J Aerosol Med Pulm Drug Deliv
Journal subject:
Drug Therapy
Year:
2021
Document Type:
Article
Affiliation country:
Jamp.2020.1648
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