Inhalable Hydroxychloroquine Powders for Potential Treatment of COVID-19.
Identifieur interne : 000848 ( Main/Corpus ); précédent : 000847; suivant : 000849Inhalable Hydroxychloroquine Powders for Potential Treatment of COVID-19.
Auteurs : Ahmed H. Albariqi ; Rachel Yoon Kyung Chang ; Waiting Tai ; Wei-Ren Ke ; Michael Y T. Chow ; Patricia Tang ; Philip Chi Lip Kwok ; Hak-Kim ChanSource :
- Journal of aerosol medicine and pulmonary drug delivery [ 1941-2703 ] ; 2021.
English descriptors
- KwdEn :
- MESH :
- chemical , administration & dosage : Hydroxychloroquine.
- drug therapy : COVID-19.
- Administration, Inhalation, Calorimetry, Differential Scanning, Humans, Particle Size, Powders, SARS-CoV-2, X-Ray Diffraction.
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 ∼43% 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.
DOI: 10.1089/jamp.2020.1648
PubMed: 33179983
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Inhalable Hydroxychloroquine Powders for Potential Treatment of COVID-19.</title><author><name sortKey="Albariqi, Ahmed H" sort="Albariqi, Ahmed H" uniqKey="Albariqi A" first="Ahmed H" last="Albariqi">Ahmed H. Albariqi</name><affiliation><nlm:affiliation>Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>The Department of Pharmaceutics, Faculty of Pharmacy, Jazan University, Jazan, Saudi Arabia.</nlm:affiliation></affiliation></author><author><name sortKey="Chang, Rachel Yoon Kyung" sort="Chang, Rachel Yoon Kyung" uniqKey="Chang R" first="Rachel Yoon Kyung" last="Chang">Rachel Yoon Kyung Chang</name><affiliation><nlm:affiliation>Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Tai, Waiting" sort="Tai, Waiting" uniqKey="Tai W" first="Waiting" last="Tai">Waiting Tai</name><affiliation><nlm:affiliation>Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Ke, Wei Ren" sort="Ke, Wei Ren" uniqKey="Ke W" first="Wei-Ren" last="Ke">Wei-Ren Ke</name><affiliation><nlm:affiliation>Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Chow, Michael Y T" sort="Chow, Michael Y T" uniqKey="Chow M" first="Michael Y T" last="Chow">Michael Y T. Chow</name><affiliation><nlm:affiliation>Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Tang, Patricia" sort="Tang, Patricia" uniqKey="Tang P" first="Patricia" last="Tang">Patricia Tang</name><affiliation><nlm:affiliation>Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Kwok, Philip Chi Lip" sort="Kwok, Philip Chi Lip" uniqKey="Kwok P" first="Philip Chi Lip" last="Kwok">Philip Chi Lip Kwok</name><affiliation><nlm:affiliation>Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Chan, Hak Kim" sort="Chan, Hak Kim" uniqKey="Chan H" first="Hak-Kim" last="Chan">Hak-Kim Chan</name><affiliation><nlm:affiliation>Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2021">2021</date><idno type="RBID">pubmed:33179983</idno><idno type="pmid">33179983</idno><idno type="doi">10.1089/jamp.2020.1648</idno><idno type="wicri:Area/Main/Corpus">000848</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000848</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Inhalable Hydroxychloroquine Powders for Potential Treatment of COVID-19.</title><author><name sortKey="Albariqi, Ahmed H" sort="Albariqi, Ahmed H" uniqKey="Albariqi A" first="Ahmed H" last="Albariqi">Ahmed H. Albariqi</name><affiliation><nlm:affiliation>Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>The Department of Pharmaceutics, Faculty of Pharmacy, Jazan University, Jazan, Saudi Arabia.</nlm:affiliation></affiliation></author><author><name sortKey="Chang, Rachel Yoon Kyung" sort="Chang, Rachel Yoon Kyung" uniqKey="Chang R" first="Rachel Yoon Kyung" last="Chang">Rachel Yoon Kyung Chang</name><affiliation><nlm:affiliation>Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Tai, Waiting" sort="Tai, Waiting" uniqKey="Tai W" first="Waiting" last="Tai">Waiting Tai</name><affiliation><nlm:affiliation>Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Ke, Wei Ren" sort="Ke, Wei Ren" uniqKey="Ke W" first="Wei-Ren" last="Ke">Wei-Ren Ke</name><affiliation><nlm:affiliation>Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Chow, Michael Y T" sort="Chow, Michael Y T" uniqKey="Chow M" first="Michael Y T" last="Chow">Michael Y T. Chow</name><affiliation><nlm:affiliation>Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Tang, Patricia" sort="Tang, Patricia" uniqKey="Tang P" first="Patricia" last="Tang">Patricia Tang</name><affiliation><nlm:affiliation>Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Kwok, Philip Chi Lip" sort="Kwok, Philip Chi Lip" uniqKey="Kwok P" first="Philip Chi Lip" last="Kwok">Philip Chi Lip Kwok</name><affiliation><nlm:affiliation>Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Chan, Hak Kim" sort="Chan, Hak Kim" uniqKey="Chan H" first="Hak-Kim" last="Chan">Hak-Kim Chan</name><affiliation><nlm:affiliation>Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Journal of aerosol medicine and pulmonary drug delivery</title><idno type="eISSN">1941-2703</idno><imprint><date when="2021" type="published">2021</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Administration, Inhalation (MeSH)</term><term>COVID-19 (drug therapy)</term><term>Calorimetry, Differential Scanning (MeSH)</term><term>Humans (MeSH)</term><term>Hydroxychloroquine (administration & dosage)</term><term>Particle Size (MeSH)</term><term>Powders (MeSH)</term><term>SARS-CoV-2 (MeSH)</term><term>X-Ray Diffraction (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Hydroxychloroquine</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>COVID-19</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Administration, Inhalation</term><term>Calorimetry, Differential Scanning</term><term>Humans</term><term>Particle Size</term><term>Powders</term><term>SARS-CoV-2</term><term>X-Ray Diffraction</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><b><i>Background:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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)<sub>recovered</sub> and the emitted fine particle fraction (FPF<sub>emitted</sub>) of the HCQ-sul sample immediately after jet milling and the samples after conditioning at 43%, 53%, and 58% RH were similar at ∼43% 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. <b><i>Conclusion:</i></b> Inhalable crystalline powders of HCQ-sul were successfully prepared, which can be used for clinical testing as a potential inhaled COVID-19 treatment.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">33179983</PMID><DateCompleted><Year>2021</Year><Month>02</Month><Day>15</Day></DateCompleted><DateRevised><Year>2021</Year><Month>02</Month><Day>15</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1941-2703</ISSN><JournalIssue CitedMedium="Internet"><Volume>34</Volume><Issue>1</Issue><PubDate><Year>2021</Year><Month>02</Month></PubDate></JournalIssue><Title>Journal of aerosol medicine and pulmonary drug delivery</Title><ISOAbbreviation>J Aerosol Med Pulm Drug Deliv</ISOAbbreviation></Journal><ArticleTitle>Inhalable Hydroxychloroquine Powders for Potential Treatment of COVID-19.</ArticleTitle><Pagination><MedlinePgn>20-31</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1089/jamp.2020.1648</ELocationID><Abstract><AbstractText><b><i>Background:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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)<sub>recovered</sub> and the emitted fine particle fraction (FPF<sub>emitted</sub>) of the HCQ-sul sample immediately after jet milling and the samples after conditioning at 43%, 53%, and 58% RH were similar at ∼43% 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. <b><i>Conclusion:</i></b> Inhalable crystalline powders of HCQ-sul were successfully prepared, which can be used for clinical testing as a potential inhaled COVID-19 treatment.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Albariqi</LastName><ForeName>Ahmed H</ForeName><Initials>AH</Initials><AffiliationInfo><Affiliation>Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>The Department of Pharmaceutics, Faculty of Pharmacy, Jazan University, Jazan, Saudi Arabia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chang</LastName><ForeName>Rachel Yoon Kyung</ForeName><Initials>RYK</Initials><AffiliationInfo><Affiliation>Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tai</LastName><ForeName>Waiting</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ke</LastName><ForeName>Wei-Ren</ForeName><Initials>WR</Initials><AffiliationInfo><Affiliation>Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chow</LastName><ForeName>Michael Y T</ForeName><Initials>MYT</Initials><AffiliationInfo><Affiliation>Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tang</LastName><ForeName>Patricia</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kwok</LastName><ForeName>Philip Chi Lip</ForeName><Initials>PCL</Initials><AffiliationInfo><Affiliation>Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chan</LastName><ForeName>Hak-Kim</ForeName><Initials>HK</Initials><AffiliationInfo><Affiliation>Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>11</Month><Day>10</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Aerosol Med Pulm Drug Deliv</MedlineTA><NlmUniqueID>101475057</NlmUniqueID><ISSNLinking>1941-2711</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011208">Powders</NameOfSubstance></Chemical><Chemical><RegistryNumber>4QWG6N8QKH</RegistryNumber><NameOfSubstance UI="D006886">Hydroxychloroquine</NameOfSubstance></Chemical></ChemicalList><SupplMeshList><SupplMeshName Type="Protocol" UI="C000705127">COVID-19 drug treatment</SupplMeshName></SupplMeshList><CitationSubset>T</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000280" MajorTopicYN="N">Administration, Inhalation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000086382" MajorTopicYN="N">COVID-19</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002152" MajorTopicYN="N">Calorimetry, Differential Scanning</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006886" MajorTopicYN="N">Hydroxychloroquine</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010316" MajorTopicYN="N">Particle Size</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011208" MajorTopicYN="N">Powders</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000086402" MajorTopicYN="Y">SARS-CoV-2</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014961" MajorTopicYN="N">X-Ray Diffraction</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">COVID-19</Keyword><Keyword MajorTopicYN="Y">HCQ</Keyword><Keyword MajorTopicYN="Y">dry powder aerosol</Keyword><Keyword MajorTopicYN="Y">inhalable hydroxychloroquine</Keyword><Keyword MajorTopicYN="Y">jet mill</Keyword><Keyword MajorTopicYN="Y">relative humidity</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>11</Month><Day>13</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2021</Year><Month>2</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>11</Month><Day>12</Day><Hour>12</Hour><Minute>10</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">33179983</ArticleId><ArticleId 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