In Vivo-Relevant Transwell Dish-Based Dissolution Testing for Orally Inhaled Corticosteroid Products
Purpose To establish an in vivo -relevant Transwell dish-based dissolution test system for the “respirable” aerosols of inhaled corticosteroids (ICSs) using marketed inhaler products. Methods “Respirable” ≤ 5.8 or 6.5 μm aerosols of 7 ICSs from 11 inhaler products were collected onto the filter memb...
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Veröffentlicht in: | Pharmaceutical research 2019-07, Vol.36 (7), p.95-11, Article 95 |
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creator | Sakagami, Masahiro Li, Hua Venitz, Jügen |
description | Purpose
To establish an
in vivo
-relevant Transwell dish-based dissolution test system for the “respirable” aerosols of inhaled corticosteroids (ICSs) using marketed inhaler products.
Methods
“Respirable” ≤ 5.8 or 6.5 μm aerosols of 7 ICSs from 11 inhaler products were collected onto the filter membranes under the modified assembly of the cascade impactor. Their dissolution in 10 ml of the simulated lung lining fluid (sLLF) was determined over time in the Transwell dish at 37°C and ~100% relative humidity in the presence of subsequent diffusive permeation across the Transwell’s supporting membrane.
Results
While three ICSs with high-to-intermediate solubility enabled the first-order “sink” and complete dissolution in 6 h, 4 ICSs with poor solubility including fluticasone propionate (FP) resulted in the pseudo-zero-order “non-sink”, slow and limited dissolution. The aerosol dissolution rate constants (k
diss
) were derived, well-correlated with the solubility. For FP, but not for highly-soluble flunisolide (FN), dissolution was kinetically aerosol mass-dependent. However, for a given ICS, dissolution profiles were indistinguishable between the formulations and products upon comparable aerosol mass collection.
Conclusions
The
in vivo
-relevant Transwell dish-based “respirable” aerosol dissolution test system was developed, kinetically discriminative in accordance with the ICS solubility, but indistinguishable for a given ICS between the marketed products. |
doi_str_mv | 10.1007/s11095-019-2635-2 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2231930386</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2222454932</sourcerecordid><originalsourceid>FETCH-LOGICAL-c372t-bb74b2a891d3a7f0785723ab8afc33715007517dd6dc036f6b9a75a2e85bbeaa3</originalsourceid><addsrcrecordid>eNp1kV1LwzAUhoMobk5_gDdS8MabaD6apr3U-TUQJjLFu5A26dbRJTNpJ_v3pnQqCF6dA-c57_l4ATjF6BIjxK88xihjEOEMkoQySPbAEDNOYYbi930wRJzEMOUxHoAj75cIoRRn8SEYUIw4TdJkCNTERG_VxsIXXeuNNE00c9L4T13X0W3lF_BGeq261Nu6bSpropn2TWXmUWldNHWyrrfRxCxkHbCxdU1VWN9oZysVPTur2qLxx-CglLXXJ7s4Aq_3d7PxI3yaPkzG10-woJw0MM95nBOZZlhRyUvEU8YJlXkqy4JSjlm4mWGuVKIKRJMyyTPJmSQ6ZXmupaQjcNHrrp39aMOaYlX5IpwijbatF4RQnFFE0ySg53_QpW2dCdsFipCYxRklgcI9VTjrvdOlWLtqJd1WYCQ6C0RvgQgWiM4C0fWc7ZTbfKXVT8f3zwNAesCHkplr9zv6f9UvML2Rgw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2222454932</pqid></control><display><type>article</type><title>In Vivo-Relevant Transwell Dish-Based Dissolution Testing for Orally Inhaled Corticosteroid Products</title><source>SpringerLink Journals - AutoHoldings</source><creator>Sakagami, Masahiro ; Li, Hua ; Venitz, Jügen</creator><creatorcontrib>Sakagami, Masahiro ; Li, Hua ; Venitz, Jügen</creatorcontrib><description>Purpose
To establish an
in vivo
-relevant Transwell dish-based dissolution test system for the “respirable” aerosols of inhaled corticosteroids (ICSs) using marketed inhaler products.
Methods
“Respirable” ≤ 5.8 or 6.5 μm aerosols of 7 ICSs from 11 inhaler products were collected onto the filter membranes under the modified assembly of the cascade impactor. Their dissolution in 10 ml of the simulated lung lining fluid (sLLF) was determined over time in the Transwell dish at 37°C and ~100% relative humidity in the presence of subsequent diffusive permeation across the Transwell’s supporting membrane.
Results
While three ICSs with high-to-intermediate solubility enabled the first-order “sink” and complete dissolution in 6 h, 4 ICSs with poor solubility including fluticasone propionate (FP) resulted in the pseudo-zero-order “non-sink”, slow and limited dissolution. The aerosol dissolution rate constants (k
diss
) were derived, well-correlated with the solubility. For FP, but not for highly-soluble flunisolide (FN), dissolution was kinetically aerosol mass-dependent. However, for a given ICS, dissolution profiles were indistinguishable between the formulations and products upon comparable aerosol mass collection.
Conclusions
The
in vivo
-relevant Transwell dish-based “respirable” aerosol dissolution test system was developed, kinetically discriminative in accordance with the ICS solubility, but indistinguishable for a given ICS between the marketed products.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1007/s11095-019-2635-2</identifier><identifier>PMID: 31073686</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Aerosols ; Biochemistry ; Biomedical and Life Sciences ; Biomedical Engineering and Bioengineering ; Biomedicine ; Corticoids ; Corticosteroids ; Dissolution ; Fluticasone ; Formulations ; Immunomodulators ; Lungs ; Medical Law ; Membranes ; Pharmacology/Toxicology ; Pharmacy ; Propionic acid ; Relative humidity ; Research Paper ; Solubility ; Test systems</subject><ispartof>Pharmaceutical research, 2019-07, Vol.36 (7), p.95-11, Article 95</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2019</rights><rights>Pharmaceutical Research is a copyright of Springer, (2019). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-bb74b2a891d3a7f0785723ab8afc33715007517dd6dc036f6b9a75a2e85bbeaa3</citedby><cites>FETCH-LOGICAL-c372t-bb74b2a891d3a7f0785723ab8afc33715007517dd6dc036f6b9a75a2e85bbeaa3</cites><orcidid>0000-0002-1387-3009</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11095-019-2635-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11095-019-2635-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31073686$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sakagami, Masahiro</creatorcontrib><creatorcontrib>Li, Hua</creatorcontrib><creatorcontrib>Venitz, Jügen</creatorcontrib><title>In Vivo-Relevant Transwell Dish-Based Dissolution Testing for Orally Inhaled Corticosteroid Products</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><addtitle>Pharm Res</addtitle><description>Purpose
To establish an
in vivo
-relevant Transwell dish-based dissolution test system for the “respirable” aerosols of inhaled corticosteroids (ICSs) using marketed inhaler products.
Methods
“Respirable” ≤ 5.8 or 6.5 μm aerosols of 7 ICSs from 11 inhaler products were collected onto the filter membranes under the modified assembly of the cascade impactor. Their dissolution in 10 ml of the simulated lung lining fluid (sLLF) was determined over time in the Transwell dish at 37°C and ~100% relative humidity in the presence of subsequent diffusive permeation across the Transwell’s supporting membrane.
Results
While three ICSs with high-to-intermediate solubility enabled the first-order “sink” and complete dissolution in 6 h, 4 ICSs with poor solubility including fluticasone propionate (FP) resulted in the pseudo-zero-order “non-sink”, slow and limited dissolution. The aerosol dissolution rate constants (k
diss
) were derived, well-correlated with the solubility. For FP, but not for highly-soluble flunisolide (FN), dissolution was kinetically aerosol mass-dependent. However, for a given ICS, dissolution profiles were indistinguishable between the formulations and products upon comparable aerosol mass collection.
Conclusions
The
in vivo
-relevant Transwell dish-based “respirable” aerosol dissolution test system was developed, kinetically discriminative in accordance with the ICS solubility, but indistinguishable for a given ICS between the marketed products.</description><subject>Aerosols</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering and Bioengineering</subject><subject>Biomedicine</subject><subject>Corticoids</subject><subject>Corticosteroids</subject><subject>Dissolution</subject><subject>Fluticasone</subject><subject>Formulations</subject><subject>Immunomodulators</subject><subject>Lungs</subject><subject>Medical Law</subject><subject>Membranes</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacy</subject><subject>Propionic acid</subject><subject>Relative humidity</subject><subject>Research Paper</subject><subject>Solubility</subject><subject>Test systems</subject><issn>0724-8741</issn><issn>1573-904X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNp1kV1LwzAUhoMobk5_gDdS8MabaD6apr3U-TUQJjLFu5A26dbRJTNpJ_v3pnQqCF6dA-c57_l4ATjF6BIjxK88xihjEOEMkoQySPbAEDNOYYbi930wRJzEMOUxHoAj75cIoRRn8SEYUIw4TdJkCNTERG_VxsIXXeuNNE00c9L4T13X0W3lF_BGeq261Nu6bSpropn2TWXmUWldNHWyrrfRxCxkHbCxdU1VWN9oZysVPTur2qLxx-CglLXXJ7s4Aq_3d7PxI3yaPkzG10-woJw0MM95nBOZZlhRyUvEU8YJlXkqy4JSjlm4mWGuVKIKRJMyyTPJmSQ6ZXmupaQjcNHrrp39aMOaYlX5IpwijbatF4RQnFFE0ySg53_QpW2dCdsFipCYxRklgcI9VTjrvdOlWLtqJd1WYCQ6C0RvgQgWiM4C0fWc7ZTbfKXVT8f3zwNAesCHkplr9zv6f9UvML2Rgw</recordid><startdate>20190701</startdate><enddate>20190701</enddate><creator>Sakagami, Masahiro</creator><creator>Li, Hua</creator><creator>Venitz, Jügen</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-1387-3009</orcidid></search><sort><creationdate>20190701</creationdate><title>In Vivo-Relevant Transwell Dish-Based Dissolution Testing for Orally Inhaled Corticosteroid Products</title><author>Sakagami, Masahiro ; Li, Hua ; Venitz, Jügen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-bb74b2a891d3a7f0785723ab8afc33715007517dd6dc036f6b9a75a2e85bbeaa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Aerosols</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedical Engineering and Bioengineering</topic><topic>Biomedicine</topic><topic>Corticoids</topic><topic>Corticosteroids</topic><topic>Dissolution</topic><topic>Fluticasone</topic><topic>Formulations</topic><topic>Immunomodulators</topic><topic>Lungs</topic><topic>Medical Law</topic><topic>Membranes</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacy</topic><topic>Propionic acid</topic><topic>Relative humidity</topic><topic>Research Paper</topic><topic>Solubility</topic><topic>Test systems</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sakagami, Masahiro</creatorcontrib><creatorcontrib>Li, Hua</creatorcontrib><creatorcontrib>Venitz, Jügen</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Pharmaceutical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sakagami, Masahiro</au><au>Li, Hua</au><au>Venitz, Jügen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In Vivo-Relevant Transwell Dish-Based Dissolution Testing for Orally Inhaled Corticosteroid Products</atitle><jtitle>Pharmaceutical research</jtitle><stitle>Pharm Res</stitle><addtitle>Pharm Res</addtitle><date>2019-07-01</date><risdate>2019</risdate><volume>36</volume><issue>7</issue><spage>95</spage><epage>11</epage><pages>95-11</pages><artnum>95</artnum><issn>0724-8741</issn><eissn>1573-904X</eissn><abstract>Purpose
To establish an
in vivo
-relevant Transwell dish-based dissolution test system for the “respirable” aerosols of inhaled corticosteroids (ICSs) using marketed inhaler products.
Methods
“Respirable” ≤ 5.8 or 6.5 μm aerosols of 7 ICSs from 11 inhaler products were collected onto the filter membranes under the modified assembly of the cascade impactor. Their dissolution in 10 ml of the simulated lung lining fluid (sLLF) was determined over time in the Transwell dish at 37°C and ~100% relative humidity in the presence of subsequent diffusive permeation across the Transwell’s supporting membrane.
Results
While three ICSs with high-to-intermediate solubility enabled the first-order “sink” and complete dissolution in 6 h, 4 ICSs with poor solubility including fluticasone propionate (FP) resulted in the pseudo-zero-order “non-sink”, slow and limited dissolution. The aerosol dissolution rate constants (k
diss
) were derived, well-correlated with the solubility. For FP, but not for highly-soluble flunisolide (FN), dissolution was kinetically aerosol mass-dependent. However, for a given ICS, dissolution profiles were indistinguishable between the formulations and products upon comparable aerosol mass collection.
Conclusions
The
in vivo
-relevant Transwell dish-based “respirable” aerosol dissolution test system was developed, kinetically discriminative in accordance with the ICS solubility, but indistinguishable for a given ICS between the marketed products.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>31073686</pmid><doi>10.1007/s11095-019-2635-2</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-1387-3009</orcidid></addata></record> |
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source | SpringerLink Journals - AutoHoldings |
subjects | Aerosols Biochemistry Biomedical and Life Sciences Biomedical Engineering and Bioengineering Biomedicine Corticoids Corticosteroids Dissolution Fluticasone Formulations Immunomodulators Lungs Medical Law Membranes Pharmacology/Toxicology Pharmacy Propionic acid Relative humidity Research Paper Solubility Test systems |
title | In Vivo-Relevant Transwell Dish-Based Dissolution Testing for Orally Inhaled Corticosteroid Products |
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