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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Data on the stability of darunavir/cobicistat suspension after tablet manipulation</title><author><name sortKey="Zanon, D" sort="Zanon, D" uniqKey="Zanon D" first="D." last="Zanon">D. Zanon</name><affiliation><nlm:aff id="aff0001">Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy</nlm:aff></affiliation></author><author><name sortKey="Manca, A" sort="Manca, A" uniqKey="Manca A" first="A." last="Manca">A. Manca</name><affiliation><nlm:aff id="aff0002">Laboratory of Clinical Pharmacology and Pharmacogenetics, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy</nlm:aff></affiliation></author><author><name sortKey="De Nicol, A" sort="De Nicol, A" uniqKey="De Nicol A" first="A." last="De Nicol">A. De Nicol</name><affiliation><nlm:aff id="aff0002">Laboratory of Clinical Pharmacology and Pharmacogenetics, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy</nlm:aff></affiliation></author><author><name sortKey="D Avolio, A" sort="D Avolio, A" uniqKey="D Avolio A" first="A." last="D'Avolio">A. D'Avolio</name><affiliation><nlm:aff id="aff0002">Laboratory of Clinical Pharmacology and Pharmacogenetics, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy</nlm:aff></affiliation></author><author><name sortKey="Musazzi, U M" sort="Musazzi, U M" uniqKey="Musazzi U" first="U. M." last="Musazzi">U. M. Musazzi</name><affiliation><nlm:aff id="aff0003">Department of Pharmaceutical Sciences, Università degli Studi di Milano, Via Giuseppe Colombo, 71, 20133 Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Cilurzo, F" sort="Cilurzo, F" uniqKey="Cilurzo F" first="F." last="Cilurzo">F. Cilurzo</name><affiliation><nlm:aff id="aff0003">Department of Pharmaceutical Sciences, Università degli Studi di Milano, Via Giuseppe Colombo, 71, 20133 Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Maximova, N" sort="Maximova, N" uniqKey="Maximova N" first="N." last="Maximova">N. Maximova</name><affiliation><nlm:aff id="aff0001">Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy</nlm:aff></affiliation></author><author><name sortKey="Tomasello, C" sort="Tomasello, C" uniqKey="Tomasello C" first="C." last="Tomasello">C. Tomasello</name><affiliation><nlm:aff id="aff0004">S.C. Farmacie Ospedaliere - Ospedale M. Vittoria - Asl Città di Torino, Turin, Italy</nlm:aff></affiliation></author><author><name sortKey="Minghetti, P" sort="Minghetti, P" uniqKey="Minghetti P" first="P." last="Minghetti">P. Minghetti</name><affiliation><nlm:aff id="aff0003">Department of Pharmaceutical Sciences, Università degli Studi di Milano, Via Giuseppe Colombo, 71, 20133 Milan, Italy</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmc">7152873</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152873</idno><idno type="RBID">PMC:7152873</idno><idno type="doi">10.1016/j.dib.2020.105552</idno><idno type="pmid">NONE</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000290</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000290</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Data on the stability of darunavir/cobicistat suspension after tablet manipulation</title><author><name sortKey="Zanon, D" sort="Zanon, D" uniqKey="Zanon D" first="D." last="Zanon">D. Zanon</name><affiliation><nlm:aff id="aff0001">Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy</nlm:aff></affiliation></author><author><name sortKey="Manca, A" sort="Manca, A" uniqKey="Manca A" first="A." last="Manca">A. Manca</name><affiliation><nlm:aff id="aff0002">Laboratory of Clinical Pharmacology and Pharmacogenetics, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy</nlm:aff></affiliation></author><author><name sortKey="De Nicol, A" sort="De Nicol, A" uniqKey="De Nicol A" first="A." last="De Nicol">A. De Nicol</name><affiliation><nlm:aff id="aff0002">Laboratory of Clinical Pharmacology and Pharmacogenetics, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy</nlm:aff></affiliation></author><author><name sortKey="D Avolio, A" sort="D Avolio, A" uniqKey="D Avolio A" first="A." last="D'Avolio">A. D'Avolio</name><affiliation><nlm:aff id="aff0002">Laboratory of Clinical Pharmacology and Pharmacogenetics, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy</nlm:aff></affiliation></author><author><name sortKey="Musazzi, U M" sort="Musazzi, U M" uniqKey="Musazzi U" first="U. M." last="Musazzi">U. M. Musazzi</name><affiliation><nlm:aff id="aff0003">Department of Pharmaceutical Sciences, Università degli Studi di Milano, Via Giuseppe Colombo, 71, 20133 Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Cilurzo, F" sort="Cilurzo, F" uniqKey="Cilurzo F" first="F." last="Cilurzo">F. Cilurzo</name><affiliation><nlm:aff id="aff0003">Department of Pharmaceutical Sciences, Università degli Studi di Milano, Via Giuseppe Colombo, 71, 20133 Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Maximova, N" sort="Maximova, N" uniqKey="Maximova N" first="N." last="Maximova">N. Maximova</name><affiliation><nlm:aff id="aff0001">Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy</nlm:aff></affiliation></author><author><name sortKey="Tomasello, C" sort="Tomasello, C" uniqKey="Tomasello C" first="C." last="Tomasello">C. Tomasello</name><affiliation><nlm:aff id="aff0004">S.C. Farmacie Ospedaliere - Ospedale M. Vittoria - Asl Città di Torino, Turin, Italy</nlm:aff></affiliation></author><author><name sortKey="Minghetti, P" sort="Minghetti, P" uniqKey="Minghetti P" first="P." last="Minghetti">P. Minghetti</name><affiliation><nlm:aff id="aff0003">Department of Pharmaceutical Sciences, Università degli Studi di Milano, Via Giuseppe Colombo, 71, 20133 Milan, Italy</nlm:aff></affiliation></author></analytic><series><title level="j">Data in Brief</title><idno type="eISSN">2352-3409</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The COVID-19 outbreak is now one of the most critical crises to manage for most of the national healthcare systems in the world. In the absence of authorised pharmacological treatments, many antiretrovirals, including darunavir/cobicistat fixed combination, were used off-label in the hospital wards as life-treating medicines for COVID-19 patients. Unfortunately, for most of them, the drug products available on the market are not designed to be administered by a nasogastric tube to inpatients of intensive care units. Therefore, their manipulation, even if it can strongly affect the product quality, is necessary for the preparation of suspension to meet patients’ need. In this situation, it is urgent to provide data and guidance to support hospital pharmacist and clinicians in their activity. The data in this article indicate that darunavir/cobicistat suspensions compounded by pharmacists using as active ingredient a commercially available tablet can be stable at least for one week.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Minghetti, P" uniqKey="Minghetti P">P. Minghetti</name></author><author><name sortKey="Pantano, D" uniqKey="Pantano D">D. Pantano</name></author><author><name sortKey="Gennari, C G M" uniqKey="Gennari C">C.G.M. Gennari</name></author><author><name sortKey="Casiraghi, A" uniqKey="Casiraghi A">A. Casiraghi</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="D Avolio, A" uniqKey="D Avolio A">A. D'Avolio</name></author><author><name sortKey="Baietto, L" uniqKey="Baietto L">L. Baietto</name></author><author><name sortKey="Siccardi, M" uniqKey="Siccardi M">M. Siccardi</name></author><author><name sortKey="Sciandra, M" uniqKey="Sciandra M">M. Sciandra</name></author><author><name sortKey="Simiele, M" uniqKey="Simiele M">M. Simiele</name></author><author><name sortKey="Oddone, V" uniqKey="Oddone V">V. Oddone</name></author><author><name sortKey="Bonora, S" uniqKey="Bonora S">S. Bonora</name></author><author><name sortKey="Di Perri, G" uniqKey="Di Perri G">G. Di Perri</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="data-paper"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Data Brief</journal-id><journal-id journal-id-type="iso-abbrev">Data Brief</journal-id><journal-title-group><journal-title>Data in Brief</journal-title></journal-title-group><issn pub-type="epub">2352-3409</issn><publisher><publisher-name>The Author(s). Published by Elsevier Inc.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmc">7152873</article-id><article-id pub-id-type="publisher-id">S2352-3409(20)30446-7</article-id><article-id pub-id-type="doi">10.1016/j.dib.2020.105552</article-id><article-id pub-id-type="publisher-id">105552</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Data on the stability of darunavir/cobicistat suspension after tablet manipulation</article-title></title-group><contrib-group><contrib contrib-type="author" id="au0001"><name><surname>Zanon</surname><given-names>D.</given-names></name><xref rid="aff0001" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au0002"><name><surname>Manca</surname><given-names>A.</given-names></name><xref rid="aff0002" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au0003"><name><surname>De Nicolò</surname><given-names>A.</given-names></name><xref rid="aff0002" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au0004"><name><surname>D'Avolio</surname><given-names>A.</given-names></name><xref rid="aff0002" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au0005"><name><surname>Musazzi</surname><given-names>U.M.</given-names></name><xref rid="aff0003" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="au0006"><name><surname>Cilurzo</surname><given-names>F.</given-names></name><xref rid="aff0003" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="au0007"><name><surname>Maximova</surname><given-names>N.</given-names></name><xref rid="aff0001" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au0008"><name><surname>Tomasello</surname><given-names>C.</given-names></name><xref rid="aff0004" ref-type="aff">d</xref></contrib><contrib contrib-type="author" id="au0009"><name><surname>Minghetti</surname><given-names>P.</given-names></name><email>paola.minghetti@unimi.it</email><xref rid="aff0003" ref-type="aff">c</xref><xref rid="cor0001" ref-type="corresp">⁎</xref></contrib></contrib-group><aff id="aff0001"><label>a</label>Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy</aff><aff id="aff0002"><label>b</label>Laboratory of Clinical Pharmacology and Pharmacogenetics, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy</aff><aff id="aff0003"><label>c</label>Department of Pharmaceutical Sciences, Università degli Studi di Milano, Via Giuseppe Colombo, 71, 20133 Milan, Italy</aff><aff id="aff0004"><label>d</label>S.C. Farmacie Ospedaliere - Ospedale M. Vittoria - Asl Città di Torino, Turin, Italy</aff><author-notes><corresp id="cor0001"><label>⁎</label>Corresponding author: Prof. Paola Minghetti, PhD, Department of Pharmaceutical Science, Università degli Studi di Milano, Via Giuseppe Colombo, 71, 20133 Milano (Italy), Phone: +39 02 503 24639, Fax: +39 02 503 24657. <email>paola.minghetti@unimi.it</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>12</day><month>4</month><year>2020</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="epub"><day>12</day><month>4</month><year>2020</year></pub-date><elocation-id>105552</elocation-id><history><date date-type="received"><day>27</day><month>3</month><year>2020</year></date><date date-type="rev-recd"><day>3</day><month>4</month><year>2020</year></date><date date-type="accepted"><day>6</day><month>4</month><year>2020</year></date></history><permissions><copyright-statement>© 2020 The Author(s). Published by Elsevier Inc.</copyright-statement><copyright-year>2020</copyright-year><copyright-holder></copyright-holder><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions><abstract id="abs0001"><p>The COVID-19 outbreak is now one of the most critical crises to manage for most of the national healthcare systems in the world. In the absence of authorised pharmacological treatments, many antiretrovirals, including darunavir/cobicistat fixed combination, were used off-label in the hospital wards as life-treating medicines for COVID-19 patients. Unfortunately, for most of them, the drug products available on the market are not designed to be administered by a nasogastric tube to inpatients of intensive care units. Therefore, their manipulation, even if it can strongly affect the product quality, is necessary for the preparation of suspension to meet patients’ need. In this situation, it is urgent to provide data and guidance to support hospital pharmacist and clinicians in their activity. The data in this article indicate that darunavir/cobicistat suspensions compounded by pharmacists using as active ingredient a commercially available tablet can be stable at least for one week.</p></abstract><kwd-group id="keys0001"><title>Keywords</title><kwd>COVID-19</kwd><kwd>Medicament manipulation</kwd><kwd>Nasogastric tube</kwd><kwd>Darunavir</kwd><kwd>Cobicistat</kwd></kwd-group></article-meta></front><body><p id="para0001"><bold>Specifications Table</bold><table-wrap position="float" id="utbl0001"><table frame="hsides" rules="groups"><tbody><tr><td valign="top"><bold>Subject</bold></td><td valign="top">Pharmacology, Toxicology and Pharmaceutical Science</td></tr><tr><td valign="top"><bold>Specific subject area</bold></td><td valign="top">Pharmaceutical Science</td></tr><tr><td valign="top"><bold>Type of data</bold></td><td valign="top">Table, Figure, Text</td></tr><tr><td valign="top"><bold>How data were acquired</bold></td><td valign="top">High pressure liquid chromatography (HPLC)</td></tr><tr><td valign="top"><bold>Data format</bold></td><td valign="top">Raw and analysed</td></tr><tr><td valign="top"><bold>Parameters for data collection</bold></td><td valign="top">Data on darunavir/cobicistat stability in suspension through one week from the preparation after storage at 4° and room temperature</td></tr><tr><td valign="top"><bold>Description of data collection</bold></td><td valign="top">The drug suspension was prepared in a hospital pharmacy by manipulating the darunavir/cobicistat tablet. The drug stability in two-vehicle suspensions was tested at different storage conditions (4°C, RT) for one week. The samples at different time points were analysed by HPLC.</td></tr><tr><td valign="top"><bold>Data source location</bold></td><td valign="top">Turin, Italy</td></tr><tr><td valign="top"><bold>Data accessibility</bold></td><td valign="top">Analysed data with the article.<break></break>Raw data and chromatogram with supplementary materials.</td></tr></tbody></table></table-wrap></p><p id="para0002"><bold>Value of the Data</bold><list list-type="simple" id="celist0001"><list-item id="celistitem0001"><label>•</label><p id="para0003">The data provide evidence on the darunavir/cobicistat chemical stability when they are suspended in different vehicles and stored for one week at different conditions.</p></list-item><list-item id="celistitem0002"><label>•</label><p id="para0004">The data can be useful to healthcare professionals that are trying to fight against the COVID-19 outbreak</p></list-item><list-item id="celistitem0003"><label>•</label><p id="para0005">These data can support further clinical studies focused on investigating the effectiveness of darunavir/cobicistat against COVID-19, especially when the commercial-available drug product has to be manipulated to meet clinical needs.</p></list-item><list-item id="celistitem0004"><label>•</label><p id="para0006">The data are insights for further studies focused on the development of new dosage forms indicated for inpatient of intensive care units.</p></list-item></list></p><sec id="sec0001"><label>1</label><title>Data Description</title><p id="para0007">One of the possible pharmacological treatment of COVID-19 patients resides in the administration of antiretroviral medicines <xref rid="bib0001" ref-type="bibr">[1]</xref>. The situation is complicated by the absence of <italic>ad hoc</italic> authorised pharmacological therapies. Many antivirals, including darunavir and cobicistat, were used off-label in the hospital wards as life-treating medicines for COVID-19 patients. Unfortunately, their manipulation is sometimes necessary because they are not always formulated to be administered to non-cooperative patients, like those in intensive care units. Thus, the activity of hospital pharmacists for the compounding of extemporaneous suspension by manipulation of authorized medicinal products is crucial to provide such life-treating treatments to the hospital wards <xref rid="bib0002" ref-type="bibr">[2]</xref>. However, the manipulation of medicines can alter their quality profile with potential impact on the efficacy and safety of the pharmacological treatment. Therefore, such compounding activities must be guided by the provisions of the Good Compounding Practice and by other available technical guidelines to assure the required quality and the stability over time of the preparation <xref rid="bib0003" ref-type="bibr">[3]</xref>.</p><p id="para0008">For example, the darunavir/cobicistat fixed combination was authorised in the EU as film-coated tablets (i.e. Rezolsta®), which cannot be administered to inpatients by using a nasogastric tube. The compounding activity of pharmacists consists of the grinding of the dosage forms and the preparation of a stable suspension. Herein, the chemical stability data of darunavir and cobicistat suspended in two different vehicles, namely a commercially available base vehicle (Syrspend®) and a 1% w/v carboxymethyl cellulose (CMC) aqueous suspension, is presented.</p><p id="para0009"><xref rid="tbl0001" ref-type="table">Tables 1</xref>and <xref rid="tbl0002" ref-type="table">2</xref>reported the data on both drug assay obtained storing an extemporaneous suspension of the powder obtained by the manipulation of the fixed drug combination at 4°C and room temperature.<table-wrap position="float" id="tbl0001"><label>Table 1</label><caption><p>Data on the chemical stability of darunavir and cobicistat in Syrspend®-based extemporaneous suspension when stored through one week at 4°C or at room temperature (RT; ≈25°C) expressed as mean percentage and relative standard deviation (RSD%).</p></caption><alt-text id="alt0001">Table 1</alt-text><table frame="hsides" rules="groups"><thead><tr><th rowspan="2" align="left" valign="top">Storage condition</th><th rowspan="2" align="left" valign="top">Sampling times (days)</th><th colspan="2" align="left" valign="top">Drug assay (%)</th><th colspan="2" align="left" valign="top">RSD (%)</th></tr><tr><th valign="top"><italic>Darunavir</italic></th><th valign="top"><italic>Cobicistat</italic></th><th valign="top"><italic>Darunavir</italic></th><th valign="top"><italic>Cobicistat</italic></th></tr></thead><tbody><tr><td rowspan="3" align="left" valign="top">at 4°C</td><td valign="top">0</td><td valign="top">100.0</td><td valign="top">100.0</td><td valign="top">7.4%</td><td valign="top">7.0%</td></tr><tr><td valign="top">3</td><td valign="top">120.2</td><td valign="top">121.8</td><td valign="top">12.5%</td><td valign="top">7.8%</td></tr><tr><td valign="top">7</td><td valign="top">120.4</td><td valign="top">120.0</td><td valign="top">8.5%</td><td valign="top">8.2%</td></tr><tr><td rowspan="3" align="left" valign="top">at RT</td><td valign="top">0</td><td valign="top">100.0</td><td valign="top">100.0</td><td valign="top">7.4%</td><td valign="top">7.0%</td></tr><tr><td valign="top">3</td><td valign="top">112.5</td><td valign="top">111.4</td><td valign="top">17.9%</td><td valign="top">9.0%</td></tr><tr><td valign="top">7</td><td valign="top">104.3</td><td valign="top">104.6</td><td valign="top">1.9%</td><td valign="top">2.1%</td></tr></tbody></table></table-wrap><table-wrap position="float" id="tbl0002"><label>Table 2</label><caption><p>Data on the chemical stability of darunavir and cobicistat in CMC-based extemporaneous suspension when stored through one week at 4°C or RT (≈25°C) expressed as mean percentage and relative standard deviation (RSD%).</p></caption><alt-text id="alt0002">Table 2</alt-text><table frame="hsides" rules="groups"><thead><tr><th rowspan="2" align="left" valign="top">Storage condition</th><th rowspan="2" align="left" valign="top">Sampling times (days)</th><th colspan="2" align="left" valign="top">Drug assay (%)</th><th colspan="2" align="left" valign="top">RSD (%)</th></tr><tr><th valign="top"><italic>Darunavir</italic></th><th valign="top"><italic>Cobicistat</italic></th><th valign="top"><italic>Darunavir</italic></th><th valign="top"><italic>Cobicistat</italic></th></tr></thead><tbody><tr><td rowspan="3" align="left" valign="top">at 4°C</td><td valign="top">0</td><td valign="top">100.0</td><td valign="top">100.0</td><td valign="top">1.9%</td><td valign="top">2.5%</td></tr><tr><td valign="top">3</td><td valign="top">93.4</td><td valign="top">92.8</td><td valign="top">11.4%</td><td valign="top">4.2%</td></tr><tr><td valign="top">7</td><td valign="top">105.4</td><td valign="top">91.1</td><td valign="top">22.4%</td><td valign="top">2.4%</td></tr><tr><td rowspan="3" align="left" valign="top">at RT.</td><td valign="top">0</td><td valign="top">100.0</td><td valign="top">100.0</td><td valign="top">1.9%</td><td valign="top">2.5%</td></tr><tr><td valign="top">3</td><td valign="top">115.6</td><td valign="top">113.7</td><td valign="top">3.6%</td><td valign="top">2.8%</td></tr><tr><td valign="top">7</td><td valign="top">123.0</td><td valign="top">106.4</td><td valign="top">13.3%</td><td valign="top">7.3%</td></tr></tbody></table></table-wrap></p><p id="para0010">The high-variability of data obtained by Syrspend®-based extemporaneous suspension can be justified since its sampling resulted more complex than CMC one due to the higher viscosity. Nevertheless, the data show that both drugs remained within ± 20% of the initial value. Such data are a proof-of-concept that both drug substances are chemically stable in the suspension over one week, regardless of the vehicle and the storage condition.</p></sec><sec id="sec0002"><label>2</label><title>Experimental Design, Materials, and Methods</title><sec id="sec0003"><label>2.1</label><title>Materials</title><p id="para0011">Rezolsta® 800 mg/150 mg film-coated tablets (Janssen-Cilag International NV, I). <italic>Tablet core</italic>: hypromellose, colloidal silicon dioxide, silicified microcrystalline cellulose, crospovidone, magnesium stearate. <italic>Tablet film-coat</italic>: polyvinyl alcohol–partially hydrolysed, macrogol 3350, titanium dioxide, talc, iron oxide red, iron oxide black <xref rid="bib0004" ref-type="bibr">[4]</xref>.</p><p id="para0012">Sodium carboxymethyl cellulose (CMC), trisodium citrate dihydrate, and citric acid were purchased by Farmalabor (I). Syrspend® was purchased by Fagron Italia. All other chemicals/solvents used in the study were either analytical grade and used without further purification or EM grade.</p></sec><sec id="sec0004"><label>2.2</label><title>Suspension preparation</title><p id="para0013">Two tablets of Rezolsta® were crushed in a mortar to obtain a fine and homogenous powder. Then, the powder was precisely weighed and loaded in a 50-ml syringe. Using a female-female Luer-lock connector, the syringe was linked to another one containing 20-mL of the suspension vehicle. Syrspend® and 1% w/v CMC solution in pH 4.2 citrate buffer were used as vehicles. The vehicle volume was set up to obtain a final suspension containing 20 mg/ml of darunavir and 3.75 mg/ml of cobicistat. Moving the syringe pluggers, the powder and the solution had mixed each other to reach a homogenous whiteish suspension (appx. 50 syringe complete movements).</p></sec><sec id="sec0005"><label>2.3</label><title>Stability studies</title><p id="para0014">Aliquots of the suspensions (1.5 mL each) were stored at both 4°C and RT for one week. At fixed sampling times (0, 3, 7 days), the aliquots of each suspension were heated to RT, if necessary, and mixed by a vortex. The samples were diluted 1:1 with a mixture of acetonitrile/water 40/60 v/v, mixed by vortex and, then, sonicated until a homogeneous suspension was obtained. The sample was split into three replicates diluted 1:125 with a mixture of acetonitrile/water 40/60 v/v. The obtained dilutions were sonicated and mixed by mechanical agitator for 30 min before being analysed in HPLC.</p></sec><sec id="sec0006"><label>2.4</label><title>HPLC method</title><p id="para0015">The method was developed and validated modifying a previous published method for plasma analyses <xref rid="bib0005" ref-type="bibr">[5]</xref>. The analysis was carried out with a liquid chromatographer Waters 2695 HPLC system (Milan, Italy) coupled with a 2998 PDA detector. HPLC-PDA system was controlled by Empower 2 Pro software (version year 2005; Waters). A chromatographic column Luna 5 µm C18 (150 × 4.6 mm; Phenomenex, US), protected by a C18 security guard (4.0 × 3.0 mm; Phenomenex, US) was used for chromatographic separation. The temperature Control Module II (Waters) was set at 45°C. the run was performed at 1 mL/min and the temperature was set at 45°C; the mobile phase was composed of solvent A (KH<sub>2</sub>PO<sub>4</sub> 50 mM with orthophosphoric acid, pH = 3.23) and solvent B (acetonitrile). The selected wavelength to quantify each drug was: 267 nm for Darunavir and 241 nm for Cobicistat. The runtime was 28 minutes. Chromatographic Condition (Gradient) were set as shown in <xref rid="tbl0003" ref-type="table">Table 3</xref>. Chromatograms of placebo and drug-loaded suspension vehicles were reported in <bold>Supplementary materials</bold>.<table-wrap position="float" id="tbl0003"><label>Table 3</label><caption><p>Chromatographic Condition (Gradient)</p></caption><alt-text id="alt0003">Table 3</alt-text><table frame="hsides" rules="groups"><thead><tr><th valign="top">Time (min)</th><th valign="top">Solvent A %</th><th valign="top">Solvent B %</th><th valign="top">Flow (mL/min)</th></tr></thead><tbody><tr><td valign="top">0.0</td><td valign="top">70</td><td valign="top">30</td><td valign="top">1</td></tr><tr><td valign="top">5.0</td><td valign="top">61</td><td valign="top">39</td><td valign="top">1</td></tr><tr><td valign="top">7.0</td><td valign="top">56</td><td valign="top">44</td><td valign="top">1</td></tr><tr><td valign="top">10.0</td><td valign="top">54</td><td valign="top">46</td><td valign="top">1</td></tr><tr><td valign="top">11.0</td><td valign="top">51</td><td valign="top">49</td><td valign="top">1</td></tr><tr><td valign="top">13.0</td><td valign="top">48</td><td valign="top">52</td><td valign="top">1</td></tr><tr><td valign="top">15.5</td><td valign="top">47</td><td valign="top">53</td><td valign="top">1</td></tr><tr><td valign="top">18.0</td><td valign="top">47</td><td valign="top">53</td><td valign="top">1</td></tr><tr><td valign="top">19.8</td><td valign="top">46</td><td valign="top">54</td><td valign="top">1</td></tr><tr><td valign="top">19.9</td><td valign="top">41</td><td valign="top">59</td><td valign="top">1</td></tr><tr><td valign="top">20.0</td><td valign="top">30</td><td valign="top">70</td><td valign="top">1</td></tr><tr><td valign="top">23.9</td><td valign="top">30</td><td valign="top">70</td><td valign="top">1</td></tr><tr><td valign="top">24.0</td><td valign="top">70</td><td valign="top">30</td><td valign="top">1</td></tr><tr><td valign="top">28.0</td><td valign="top">70</td><td valign="top">30</td><td valign="top">1</td></tr></tbody></table></table-wrap></p><p id="para0016">Preliminary, stress tests were performed on aliquots of the obtained extemporaneous suspensions to identified degradation patterns of both drugs. Aliquots of both suspensions were stored in the following conditions: at 96°C, at RT and 96°C after the addition of phosphoric acid pH 2.5, at RT and 96°C after the addition of ammonia pH 10. Chromatograms of the observed degradation products during stress tests were included in <bold>Supplementary materials</bold>.</p></sec></sec><sec sec-type="COI-statement"><title>Declaration of Competing Interest</title><p id="para0019">The authors declare that they have no known competing financial interests or personal relationships which have, or could be perceived to have, influenced the work reported in this article.</p></sec></body><back><ref-list id="cebibl1"><title>References</title><ref id="bib0001"><label>1</label><mixed-citation publication-type="other" id="othref0001">WHO, Q&A on COVID-19, HIV and antiretrovirals. <ext-link ext-link-type="uri" xlink:href="https://www.who.int/news-room/q-a-detail/q-a-on-covid-19-hiv-and-antiretrovirals" id="interref0002">https://www.who.int/news-room/q-a-detail/q-a-on-covid-19-hiv-and-antiretrovirals</ext-link>(accessed: 21 March 2020).</mixed-citation></ref><ref id="bib0002"><label>2</label><mixed-citation publication-type="other" id="othref0002">Council of Europe, Resolution CM/Res(2016)1 on Quality and Safety Assurance Requirements for Medicinal Products Prepared in Pharmacies for the Special Needs of Patients. <ext-link ext-link-type="uri" xlink:href="https://www.edqm.eu/sites/default/files/resolution_cm_res_2016_1_quality_and_safety_assurance_requirements_for_medicinal_products_prepared_in_pharmacies.pdf" id="interref0003">https://www.edqm.eu/sites/default/files/resolution_cm_res_2016_1_quality_and_safety_assurance_requirements_for_medicinal_products_prepared_in_pharmacies.pdf</ext-link>(accessed: 20 December 2019).</mixed-citation></ref><ref id="bib0003"><label>3</label><element-citation publication-type="journal" id="sbref0001"><person-group person-group-type="author"><name><surname>Minghetti</surname><given-names>P.</given-names></name><name><surname>Pantano</surname><given-names>D.</given-names></name><name><surname>Gennari</surname><given-names>C.G.M.</given-names></name><name><surname>Casiraghi</surname><given-names>A.</given-names></name></person-group><article-title>Regulatory framework of pharmaceutical compounding and actual developments of legislation in Europe</article-title><source>Health Policy</source><volume>117</volume><year>2014</year><fpage>328</fpage><lpage>333</lpage><pub-id pub-id-type="pmid">25110297</pub-id></element-citation></ref><ref id="bib0004"><label>4</label><mixed-citation publication-type="other" id="othref0003">EMA, Rezolsta®. <ext-link ext-link-type="uri" xlink:href="https://www.ema.europa.eu/en/medicines/human/EPAR/rezolsta" id="interref0004">https://www.ema.europa.eu/en/medicines/human/EPAR/rezolsta</ext-link>(accessed: 21 March 2020).</mixed-citation></ref><ref id="bib0005"><label>5</label><element-citation publication-type="journal" id="sbref0002"><person-group person-group-type="author"><name><surname>D'Avolio</surname><given-names>A.</given-names></name><name><surname>Baietto</surname><given-names>L.</given-names></name><name><surname>Siccardi</surname><given-names>M.</given-names></name><name><surname>Sciandra</surname><given-names>M.</given-names></name><name><surname>Simiele</surname><given-names>M.</given-names></name><name><surname>Oddone</surname><given-names>V.</given-names></name><name><surname>Bonora</surname><given-names>S.</given-names></name><name><surname>Di Perri</surname><given-names>G.</given-names></name></person-group><article-title>An HPLC-PDA method for the simultaneous quantification of the HIV integrase inhibitor raltegravir, the new nonnucleoside reverse transcriptase inhibitor etravirine, and 11 other antiretroviral agents in the plasma of HIV-infected patients</article-title><source>Ther Drug Monit.</source><volume>30</volume><year>2008</year><fpage>662</fpage><lpage>669</lpage><pub-id pub-id-type="pmid">18824956</pub-id></element-citation></ref></ref-list><sec id="sec0008" sec-type="supplementary-material"><label>Appendix</label><title>Supplementary materials</title><p id="para0017a"><supplementary-material content-type="local-data" id="ecom0001"><media xlink:href="mmc1.xml"><alt-text>Image, application 1</alt-text></media></supplementary-material><supplementary-material content-type="local-data" id="ecom0002"><media xlink:href="mmc2.pdf"><alt-text>Image, application 2</alt-text></media></supplementary-material></p></sec><fn-group><fn id="sec0007" fn-type="supplementary-material"><p id="para0001a">Supplementary material associated with this article can be found, in the online version, at <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/j.dib.2020.105552" id="interref0001">doi:10.1016/j.dib.2020.105552</ext-link>.</p></fn></fn-group></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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