Validating Whole-Airway CFD Predictions of DPI Aerosol Deposition at Multiple Flow Rates
The objective of this study was to compare aerosol deposition predictions of a new whole-airway CFD model with available in vivo data for a dry powder inhaler (DPI) considered across multiple inhalation waveforms, which affect both the particle size distribution (PSD) and particle deposition. The No...
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| Veröffentlicht in: | Journal of aerosol medicine 2016-12, Vol.29 (6), p.461-481 |
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| creator | Longest, P Worth Tian, Geng Khajeh-Hosseini-Dalasm, Navvab Hindle, Michael |
| description | The objective of this study was to compare aerosol deposition predictions of a new whole-airway CFD model with available in vivo data for a dry powder inhaler (DPI) considered across multiple inhalation waveforms, which affect both the particle size distribution (PSD) and particle deposition.
The Novolizer DPI with a budesonide formulation was selected based on the availability of 2D gamma scintigraphy data in humans for three different well-defined inhalation waveforms. Initial in vitro cascade impaction experiments were conducted at multiple constant (square-wave) particle sizing flow rates to characterize PSDs. The whole-airway CFD modeling approach implemented the experimentally determined PSDs at the point of aerosol formation in the inhaler. Complete characteristic airway geometries for an adult were evaluated through the lobar bronchi, followed by stochastic individual pathway (SIP) approximations through the tracheobronchial region and new acinar moving wall models of the alveolar region.
It was determined that the PSD used for each inhalation waveform should be based on a constant particle sizing flow rate equal to the average of the inhalation waveform's peak inspiratory flow rate (PIFR) and mean flow rate [i.e., AVG(PIFR, Mean)]. Using this technique, agreement with the in vivo data was acceptable with |
| doi_str_mv | 10.1089/jamp.2015.1281 |
| format | Article |
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The Novolizer DPI with a budesonide formulation was selected based on the availability of 2D gamma scintigraphy data in humans for three different well-defined inhalation waveforms. Initial in vitro cascade impaction experiments were conducted at multiple constant (square-wave) particle sizing flow rates to characterize PSDs. The whole-airway CFD modeling approach implemented the experimentally determined PSDs at the point of aerosol formation in the inhaler. Complete characteristic airway geometries for an adult were evaluated through the lobar bronchi, followed by stochastic individual pathway (SIP) approximations through the tracheobronchial region and new acinar moving wall models of the alveolar region.
It was determined that the PSD used for each inhalation waveform should be based on a constant particle sizing flow rate equal to the average of the inhalation waveform's peak inspiratory flow rate (PIFR) and mean flow rate [i.e., AVG(PIFR, Mean)]. Using this technique, agreement with the in vivo data was acceptable with <15% relative differences averaged across the three regions considered for all inhalation waveforms. Defining a peripheral to central deposition ratio (P/C) based on alveolar and tracheobronchial compartments, respectively, large flow-rate-dependent differences were observed, which were not evident in the original 2D in vivo data.
The agreement between the CFD predictions and in vivo data was dependent on accurate initial estimates of the PSD, emphasizing the need for a combination in vitro-in silico approach. Furthermore, use of the AVG(PIFR, Mean) value was identified as a potentially useful method for characterizing a DPI aerosol at a constant flow rate.</description><identifier>ISSN: 1941-2711</identifier><identifier>ISSN: 1941-2703</identifier><identifier>EISSN: 1941-2703</identifier><identifier>DOI: 10.1089/jamp.2015.1281</identifier><identifier>PMID: 27082824</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc</publisher><subject>Administration, Inhalation ; Adult ; Aerosols ; Bronchodilator Agents - administration & dosage ; Bronchodilator Agents - chemistry ; Bronchodilator Agents - metabolism ; Budesonide - administration & dosage ; Budesonide - chemistry ; Budesonide - metabolism ; Computer Simulation ; Drug Compounding ; Dry Powder Inhalers ; Glucocorticoids - administration & dosage ; Glucocorticoids - chemistry ; Glucocorticoids - metabolism ; Humans ; Models, Anatomic ; Original Research ; Particle Size ; Reproducibility of Results ; Respiration ; Respiratory System - anatomy & histology ; Respiratory System - metabolism ; Stochastic Processes ; Tissue Distribution</subject><ispartof>Journal of aerosol medicine, 2016-12, Vol.29 (6), p.461-481</ispartof><rights>(©) Copyright 2016, Mary Ann Liebert, Inc.</rights><rights>Copyright 2016, Mary Ann Liebert, Inc. 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c517t-146fe123772985a97d2d8ec06503164a03801d91732a57e526220c40854663773</citedby><cites>FETCH-LOGICAL-c517t-146fe123772985a97d2d8ec06503164a03801d91732a57e526220c40854663773</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,778,782,883,27911,27912</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27082824$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Longest, P Worth</creatorcontrib><creatorcontrib>Tian, Geng</creatorcontrib><creatorcontrib>Khajeh-Hosseini-Dalasm, Navvab</creatorcontrib><creatorcontrib>Hindle, Michael</creatorcontrib><title>Validating Whole-Airway CFD Predictions of DPI Aerosol Deposition at Multiple Flow Rates</title><title>Journal of aerosol medicine</title><addtitle>J Aerosol Med Pulm Drug Deliv</addtitle><description>The objective of this study was to compare aerosol deposition predictions of a new whole-airway CFD model with available in vivo data for a dry powder inhaler (DPI) considered across multiple inhalation waveforms, which affect both the particle size distribution (PSD) and particle deposition.
The Novolizer DPI with a budesonide formulation was selected based on the availability of 2D gamma scintigraphy data in humans for three different well-defined inhalation waveforms. Initial in vitro cascade impaction experiments were conducted at multiple constant (square-wave) particle sizing flow rates to characterize PSDs. The whole-airway CFD modeling approach implemented the experimentally determined PSDs at the point of aerosol formation in the inhaler. Complete characteristic airway geometries for an adult were evaluated through the lobar bronchi, followed by stochastic individual pathway (SIP) approximations through the tracheobronchial region and new acinar moving wall models of the alveolar region.
It was determined that the PSD used for each inhalation waveform should be based on a constant particle sizing flow rate equal to the average of the inhalation waveform's peak inspiratory flow rate (PIFR) and mean flow rate [i.e., AVG(PIFR, Mean)]. Using this technique, agreement with the in vivo data was acceptable with <15% relative differences averaged across the three regions considered for all inhalation waveforms. Defining a peripheral to central deposition ratio (P/C) based on alveolar and tracheobronchial compartments, respectively, large flow-rate-dependent differences were observed, which were not evident in the original 2D in vivo data.
The agreement between the CFD predictions and in vivo data was dependent on accurate initial estimates of the PSD, emphasizing the need for a combination in vitro-in silico approach. Furthermore, use of the AVG(PIFR, Mean) value was identified as a potentially useful method for characterizing a DPI aerosol at a constant flow rate.</description><subject>Administration, Inhalation</subject><subject>Adult</subject><subject>Aerosols</subject><subject>Bronchodilator Agents - administration & dosage</subject><subject>Bronchodilator Agents - chemistry</subject><subject>Bronchodilator Agents - metabolism</subject><subject>Budesonide - administration & dosage</subject><subject>Budesonide - chemistry</subject><subject>Budesonide - metabolism</subject><subject>Computer Simulation</subject><subject>Drug Compounding</subject><subject>Dry Powder Inhalers</subject><subject>Glucocorticoids - administration & dosage</subject><subject>Glucocorticoids - chemistry</subject><subject>Glucocorticoids - metabolism</subject><subject>Humans</subject><subject>Models, Anatomic</subject><subject>Original Research</subject><subject>Particle Size</subject><subject>Reproducibility of Results</subject><subject>Respiration</subject><subject>Respiratory System - anatomy & histology</subject><subject>Respiratory System - metabolism</subject><subject>Stochastic Processes</subject><subject>Tissue Distribution</subject><issn>1941-2711</issn><issn>1941-2703</issn><issn>1941-2703</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqNkc1P3DAQxS3UCijttcfKUi9csvX4Oxek1S4LSFQg1K-b5SZe8MobBzsp4r-vI-iq5dS5eKT3m6fxPITeA5kB0fWnjd32M0pAzIBq2EOHUHOoqCLs1a4HOEBvct4QIoFLto8Oiq6ppvwQ_fhmg2_t4Ltb_P0uBlfNfXqwj3ixWuLr5FrfDD52Gcc1Xl5f4LlLMceAl66P2U8StgP-PIbB98HhVYgP-MYOLr9Fr9c2ZPfu-T1CX1enXxbn1eXV2cViflk1AtRQlYXWDihTitZa2Fq1tNWuIVIQBpJbwjSBtgbFqBXKCSopJQ0nWnApyxQ7QidPvv34c-vaxnVDssH0yW9tejTRevOv0vk7cxt_GVGMhJgMjp8NUrwfXR7M1ufGhWA7F8dsQAuiVE3U_6BUltKMFfTjC3QTx9SVSxSKc8VqIXmhZk9UU66ak1vv9gZipnzNlK-Z8jVTvmXgw9-_3eF_AmW_ATZHnk8</recordid><startdate>201612</startdate><enddate>201612</enddate><creator>Longest, P Worth</creator><creator>Tian, Geng</creator><creator>Khajeh-Hosseini-Dalasm, Navvab</creator><creator>Hindle, Michael</creator><general>Mary Ann Liebert, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</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>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>201612</creationdate><title>Validating Whole-Airway CFD Predictions of DPI Aerosol Deposition at Multiple Flow Rates</title><author>Longest, P Worth ; Tian, Geng ; Khajeh-Hosseini-Dalasm, Navvab ; Hindle, Michael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c517t-146fe123772985a97d2d8ec06503164a03801d91732a57e526220c40854663773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Administration, Inhalation</topic><topic>Adult</topic><topic>Aerosols</topic><topic>Bronchodilator Agents - administration & dosage</topic><topic>Bronchodilator Agents - chemistry</topic><topic>Bronchodilator Agents - metabolism</topic><topic>Budesonide - administration & dosage</topic><topic>Budesonide - chemistry</topic><topic>Budesonide - metabolism</topic><topic>Computer Simulation</topic><topic>Drug Compounding</topic><topic>Dry Powder Inhalers</topic><topic>Glucocorticoids - administration & dosage</topic><topic>Glucocorticoids - chemistry</topic><topic>Glucocorticoids - metabolism</topic><topic>Humans</topic><topic>Models, Anatomic</topic><topic>Original Research</topic><topic>Particle Size</topic><topic>Reproducibility of Results</topic><topic>Respiration</topic><topic>Respiratory System - anatomy & histology</topic><topic>Respiratory System - metabolism</topic><topic>Stochastic Processes</topic><topic>Tissue Distribution</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Longest, P Worth</creatorcontrib><creatorcontrib>Tian, Geng</creatorcontrib><creatorcontrib>Khajeh-Hosseini-Dalasm, Navvab</creatorcontrib><creatorcontrib>Hindle, Michael</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</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><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of aerosol medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Longest, P Worth</au><au>Tian, Geng</au><au>Khajeh-Hosseini-Dalasm, Navvab</au><au>Hindle, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Validating Whole-Airway CFD Predictions of DPI Aerosol Deposition at Multiple Flow Rates</atitle><jtitle>Journal of aerosol medicine</jtitle><addtitle>J Aerosol Med Pulm Drug Deliv</addtitle><date>2016-12</date><risdate>2016</risdate><volume>29</volume><issue>6</issue><spage>461</spage><epage>481</epage><pages>461-481</pages><issn>1941-2711</issn><issn>1941-2703</issn><eissn>1941-2703</eissn><abstract>The objective of this study was to compare aerosol deposition predictions of a new whole-airway CFD model with available in vivo data for a dry powder inhaler (DPI) considered across multiple inhalation waveforms, which affect both the particle size distribution (PSD) and particle deposition.
The Novolizer DPI with a budesonide formulation was selected based on the availability of 2D gamma scintigraphy data in humans for three different well-defined inhalation waveforms. Initial in vitro cascade impaction experiments were conducted at multiple constant (square-wave) particle sizing flow rates to characterize PSDs. The whole-airway CFD modeling approach implemented the experimentally determined PSDs at the point of aerosol formation in the inhaler. Complete characteristic airway geometries for an adult were evaluated through the lobar bronchi, followed by stochastic individual pathway (SIP) approximations through the tracheobronchial region and new acinar moving wall models of the alveolar region.
It was determined that the PSD used for each inhalation waveform should be based on a constant particle sizing flow rate equal to the average of the inhalation waveform's peak inspiratory flow rate (PIFR) and mean flow rate [i.e., AVG(PIFR, Mean)]. Using this technique, agreement with the in vivo data was acceptable with <15% relative differences averaged across the three regions considered for all inhalation waveforms. Defining a peripheral to central deposition ratio (P/C) based on alveolar and tracheobronchial compartments, respectively, large flow-rate-dependent differences were observed, which were not evident in the original 2D in vivo data.
The agreement between the CFD predictions and in vivo data was dependent on accurate initial estimates of the PSD, emphasizing the need for a combination in vitro-in silico approach. Furthermore, use of the AVG(PIFR, Mean) value was identified as a potentially useful method for characterizing a DPI aerosol at a constant flow rate.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>27082824</pmid><doi>10.1089/jamp.2015.1281</doi><tpages>21</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of aerosol medicine, 2016-12, Vol.29 (6), p.461-481 |
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| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Administration, Inhalation Adult Aerosols Bronchodilator Agents - administration & dosage Bronchodilator Agents - chemistry Bronchodilator Agents - metabolism Budesonide - administration & dosage Budesonide - chemistry Budesonide - metabolism Computer Simulation Drug Compounding Dry Powder Inhalers Glucocorticoids - administration & dosage Glucocorticoids - chemistry Glucocorticoids - metabolism Humans Models, Anatomic Original Research Particle Size Reproducibility of Results Respiration Respiratory System - anatomy & histology Respiratory System - metabolism Stochastic Processes Tissue Distribution |
| title | Validating Whole-Airway CFD Predictions of DPI Aerosol Deposition at Multiple Flow Rates |
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