Absolute Quantification of Residual Solvent in Mesoporous Silica Drug Formulations Using Magic-Angle Spinning NMR Spectroscopy
Porous silica is used as a drug delivery agent to improve the bioavailability of sparsely soluble compounds. In this approach, the active pharmaceutical ingredient (API) is commonly loaded into the porous silica by incipient wetness impregnation using organic solvents. Subsequent solvent elimination...
Gespeichert in:
Veröffentlicht in: | Analytical chemistry (Washington) 2023-01, Vol.95 (3), p.1880-1887 |
---|---|
Hauptverfasser: | , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 1887 |
---|---|
container_issue | 3 |
container_start_page | 1880 |
container_title | Analytical chemistry (Washington) |
container_volume | 95 |
creator | Vanderschaeghe, Hannah Houlleberghs, Maarten Verheyden, Loes Dom, Dirk Chandran, C. Vinod Radhakrishnan, Sambhu Martens, Johan A. Breynaert, Eric |
description | Porous silica is used as a drug delivery agent to improve the bioavailability of sparsely soluble compounds. In this approach, the active pharmaceutical ingredient (API) is commonly loaded into the porous silica by incipient wetness impregnation using organic solvents. Subsequent solvent elimination is critical as the residual solvent concentration cannot exceed threshold values set by health and safety regulations (e.g., EMA/CHMP/ICH/82260/2006). For dichloromethane and methanol, for example, residual concentrations must be below 600 and 3000 ppm, respectively. Today, EU and USA Pharmacopoeias recommend tedious procedures for residual solvent quantification, requiring extraction of the solvent and subsequent quantification using capillary gas chromatography with static headspace sampling (sHS-GC). This work presents a new method based on the combination of standard addition and absolute quantification using magic-angle spinning nuclear magnetic resonance spectroscopy (MAS qNMR). The methodology was originally developed for absolute quantification of water in zeolites and has now been validated for quantification of residual solvent in drug formations using mesoporous silica loaded with ibuprofen dissolved in DCM and MeOH as test samples. Interestingly, formulations prepared using as-received or predried mesoporous silica contained 5465 versus 484.9 ppm DCM, respectively. This implies that the initial water content of the silica carrier can impact the residual solvent concentration in drug-loaded materials. This observation could provide new options to minimize the occurrence of these undesired solvents in the final formulation. |
doi_str_mv | 10.1021/acs.analchem.2c03646 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2759264632</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2769621936</sourcerecordid><originalsourceid>FETCH-LOGICAL-a376t-573a8745b865ea9ee588d39eb11eac4d7f5fd77f2d8b8e21898097094fdba4e3</originalsourceid><addsrcrecordid>eNp9kc1u1DAUhS0EokPhDRCyxIZNBv_EP1mOWgpIHRCdso4c52Zw5djBTpC64dnxMNMuWLCybH3nWPd-CL2mZE0Jo--NzWsTjLc_YFwzS7is5RO0ooKRSmrNnqIVIYRXTBFyhl7kfEcIpYTK5-iMS6EaLfgK_d50OfplBvxtMWF2g7NmdjHgOOAbyK5fjMe76H9BmLELeAs5TjHFJeOd8wXGl2nZ46uYxsX_TWb8Pbuwx1uzd7bahL0HvJtcCIfHL9ubcgE7p5htnO5fomeD8Rlenc5zdHv14fbiU3X99ePni811ZbiScyUUN1rVotNSgGkAhNY9b6CjFIytezWIoVdqYL3uNDCqG00aRZp66DtTAz9H7461U4o_F8hzO7pswXsToIzSMiUaVvbHWUHf_oPexSWVPR8o2UhGGy4LVR8pWwbJCYZ2Sm406b6lpD3oaYue9kFPe9JTYm9O5Us3Qv8YevBRAHIEDvHHj__b-QdpWKCz</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2769621936</pqid></control><display><type>article</type><title>Absolute Quantification of Residual Solvent in Mesoporous Silica Drug Formulations Using Magic-Angle Spinning NMR Spectroscopy</title><source>ACS Publications</source><creator>Vanderschaeghe, Hannah ; Houlleberghs, Maarten ; Verheyden, Loes ; Dom, Dirk ; Chandran, C. Vinod ; Radhakrishnan, Sambhu ; Martens, Johan A. ; Breynaert, Eric</creator><creatorcontrib>Vanderschaeghe, Hannah ; Houlleberghs, Maarten ; Verheyden, Loes ; Dom, Dirk ; Chandran, C. Vinod ; Radhakrishnan, Sambhu ; Martens, Johan A. ; Breynaert, Eric</creatorcontrib><description>Porous silica is used as a drug delivery agent to improve the bioavailability of sparsely soluble compounds. In this approach, the active pharmaceutical ingredient (API) is commonly loaded into the porous silica by incipient wetness impregnation using organic solvents. Subsequent solvent elimination is critical as the residual solvent concentration cannot exceed threshold values set by health and safety regulations (e.g., EMA/CHMP/ICH/82260/2006). For dichloromethane and methanol, for example, residual concentrations must be below 600 and 3000 ppm, respectively. Today, EU and USA Pharmacopoeias recommend tedious procedures for residual solvent quantification, requiring extraction of the solvent and subsequent quantification using capillary gas chromatography with static headspace sampling (sHS-GC). This work presents a new method based on the combination of standard addition and absolute quantification using magic-angle spinning nuclear magnetic resonance spectroscopy (MAS qNMR). The methodology was originally developed for absolute quantification of water in zeolites and has now been validated for quantification of residual solvent in drug formations using mesoporous silica loaded with ibuprofen dissolved in DCM and MeOH as test samples. Interestingly, formulations prepared using as-received or predried mesoporous silica contained 5465 versus 484.9 ppm DCM, respectively. This implies that the initial water content of the silica carrier can impact the residual solvent concentration in drug-loaded materials. This observation could provide new options to minimize the occurrence of these undesired solvents in the final formulation.</description><identifier>ISSN: 0003-2700</identifier><identifier>EISSN: 1520-6882</identifier><identifier>DOI: 10.1021/acs.analchem.2c03646</identifier><identifier>PMID: 36579853</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Bioavailability ; Chemistry ; Dichloromethane ; Drug delivery ; Formulations ; Gas chromatography ; Headspace ; Ibuprofen ; Magnetic resonance spectroscopy ; Moisture content ; NMR ; NMR spectroscopy ; Nuclear magnetic resonance ; Nuclear safety ; Organic solvents ; Safety regulations ; Silica ; Silicon dioxide ; Solvents ; Spectroscopy ; Spectrum analysis ; Spinning (materials) ; Water content ; Zeolites</subject><ispartof>Analytical chemistry (Washington), 2023-01, Vol.95 (3), p.1880-1887</ispartof><rights>2022 American Chemical Society</rights><rights>Copyright American Chemical Society Jan 24, 2023</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a376t-573a8745b865ea9ee588d39eb11eac4d7f5fd77f2d8b8e21898097094fdba4e3</citedby><cites>FETCH-LOGICAL-a376t-573a8745b865ea9ee588d39eb11eac4d7f5fd77f2d8b8e21898097094fdba4e3</cites><orcidid>0000-0002-0274-2759 ; 0000-0003-3499-0455 ; 0000-0003-4074-8833 ; 0000-0002-9292-2357</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.analchem.2c03646$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.analchem.2c03646$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27055,27903,27904,56716,56766</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36579853$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vanderschaeghe, Hannah</creatorcontrib><creatorcontrib>Houlleberghs, Maarten</creatorcontrib><creatorcontrib>Verheyden, Loes</creatorcontrib><creatorcontrib>Dom, Dirk</creatorcontrib><creatorcontrib>Chandran, C. Vinod</creatorcontrib><creatorcontrib>Radhakrishnan, Sambhu</creatorcontrib><creatorcontrib>Martens, Johan A.</creatorcontrib><creatorcontrib>Breynaert, Eric</creatorcontrib><title>Absolute Quantification of Residual Solvent in Mesoporous Silica Drug Formulations Using Magic-Angle Spinning NMR Spectroscopy</title><title>Analytical chemistry (Washington)</title><addtitle>Anal. Chem</addtitle><description>Porous silica is used as a drug delivery agent to improve the bioavailability of sparsely soluble compounds. In this approach, the active pharmaceutical ingredient (API) is commonly loaded into the porous silica by incipient wetness impregnation using organic solvents. Subsequent solvent elimination is critical as the residual solvent concentration cannot exceed threshold values set by health and safety regulations (e.g., EMA/CHMP/ICH/82260/2006). For dichloromethane and methanol, for example, residual concentrations must be below 600 and 3000 ppm, respectively. Today, EU and USA Pharmacopoeias recommend tedious procedures for residual solvent quantification, requiring extraction of the solvent and subsequent quantification using capillary gas chromatography with static headspace sampling (sHS-GC). This work presents a new method based on the combination of standard addition and absolute quantification using magic-angle spinning nuclear magnetic resonance spectroscopy (MAS qNMR). The methodology was originally developed for absolute quantification of water in zeolites and has now been validated for quantification of residual solvent in drug formations using mesoporous silica loaded with ibuprofen dissolved in DCM and MeOH as test samples. Interestingly, formulations prepared using as-received or predried mesoporous silica contained 5465 versus 484.9 ppm DCM, respectively. This implies that the initial water content of the silica carrier can impact the residual solvent concentration in drug-loaded materials. This observation could provide new options to minimize the occurrence of these undesired solvents in the final formulation.</description><subject>Bioavailability</subject><subject>Chemistry</subject><subject>Dichloromethane</subject><subject>Drug delivery</subject><subject>Formulations</subject><subject>Gas chromatography</subject><subject>Headspace</subject><subject>Ibuprofen</subject><subject>Magnetic resonance spectroscopy</subject><subject>Moisture content</subject><subject>NMR</subject><subject>NMR spectroscopy</subject><subject>Nuclear magnetic resonance</subject><subject>Nuclear safety</subject><subject>Organic solvents</subject><subject>Safety regulations</subject><subject>Silica</subject><subject>Silicon dioxide</subject><subject>Solvents</subject><subject>Spectroscopy</subject><subject>Spectrum analysis</subject><subject>Spinning (materials)</subject><subject>Water content</subject><subject>Zeolites</subject><issn>0003-2700</issn><issn>1520-6882</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kc1u1DAUhS0EokPhDRCyxIZNBv_EP1mOWgpIHRCdso4c52Zw5djBTpC64dnxMNMuWLCybH3nWPd-CL2mZE0Jo--NzWsTjLc_YFwzS7is5RO0ooKRSmrNnqIVIYRXTBFyhl7kfEcIpYTK5-iMS6EaLfgK_d50OfplBvxtMWF2g7NmdjHgOOAbyK5fjMe76H9BmLELeAs5TjHFJeOd8wXGl2nZ46uYxsX_TWb8Pbuwx1uzd7bahL0HvJtcCIfHL9ubcgE7p5htnO5fomeD8Rlenc5zdHv14fbiU3X99ePni811ZbiScyUUN1rVotNSgGkAhNY9b6CjFIytezWIoVdqYL3uNDCqG00aRZp66DtTAz9H7461U4o_F8hzO7pswXsToIzSMiUaVvbHWUHf_oPexSWVPR8o2UhGGy4LVR8pWwbJCYZ2Sm406b6lpD3oaYue9kFPe9JTYm9O5Us3Qv8YevBRAHIEDvHHj__b-QdpWKCz</recordid><startdate>20230124</startdate><enddate>20230124</enddate><creator>Vanderschaeghe, Hannah</creator><creator>Houlleberghs, Maarten</creator><creator>Verheyden, Loes</creator><creator>Dom, Dirk</creator><creator>Chandran, C. Vinod</creator><creator>Radhakrishnan, Sambhu</creator><creator>Martens, Johan A.</creator><creator>Breynaert, Eric</creator><general>American Chemical Society</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7TA</scope><scope>7TB</scope><scope>7TM</scope><scope>7U5</scope><scope>7U7</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0274-2759</orcidid><orcidid>https://orcid.org/0000-0003-3499-0455</orcidid><orcidid>https://orcid.org/0000-0003-4074-8833</orcidid><orcidid>https://orcid.org/0000-0002-9292-2357</orcidid></search><sort><creationdate>20230124</creationdate><title>Absolute Quantification of Residual Solvent in Mesoporous Silica Drug Formulations Using Magic-Angle Spinning NMR Spectroscopy</title><author>Vanderschaeghe, Hannah ; Houlleberghs, Maarten ; Verheyden, Loes ; Dom, Dirk ; Chandran, C. Vinod ; Radhakrishnan, Sambhu ; Martens, Johan A. ; Breynaert, Eric</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a376t-573a8745b865ea9ee588d39eb11eac4d7f5fd77f2d8b8e21898097094fdba4e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Bioavailability</topic><topic>Chemistry</topic><topic>Dichloromethane</topic><topic>Drug delivery</topic><topic>Formulations</topic><topic>Gas chromatography</topic><topic>Headspace</topic><topic>Ibuprofen</topic><topic>Magnetic resonance spectroscopy</topic><topic>Moisture content</topic><topic>NMR</topic><topic>NMR spectroscopy</topic><topic>Nuclear magnetic resonance</topic><topic>Nuclear safety</topic><topic>Organic solvents</topic><topic>Safety regulations</topic><topic>Silica</topic><topic>Silicon dioxide</topic><topic>Solvents</topic><topic>Spectroscopy</topic><topic>Spectrum analysis</topic><topic>Spinning (materials)</topic><topic>Water content</topic><topic>Zeolites</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vanderschaeghe, Hannah</creatorcontrib><creatorcontrib>Houlleberghs, Maarten</creatorcontrib><creatorcontrib>Verheyden, Loes</creatorcontrib><creatorcontrib>Dom, Dirk</creatorcontrib><creatorcontrib>Chandran, C. Vinod</creatorcontrib><creatorcontrib>Radhakrishnan, Sambhu</creatorcontrib><creatorcontrib>Martens, Johan A.</creatorcontrib><creatorcontrib>Breynaert, Eric</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Analytical chemistry (Washington)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vanderschaeghe, Hannah</au><au>Houlleberghs, Maarten</au><au>Verheyden, Loes</au><au>Dom, Dirk</au><au>Chandran, C. Vinod</au><au>Radhakrishnan, Sambhu</au><au>Martens, Johan A.</au><au>Breynaert, Eric</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Absolute Quantification of Residual Solvent in Mesoporous Silica Drug Formulations Using Magic-Angle Spinning NMR Spectroscopy</atitle><jtitle>Analytical chemistry (Washington)</jtitle><addtitle>Anal. Chem</addtitle><date>2023-01-24</date><risdate>2023</risdate><volume>95</volume><issue>3</issue><spage>1880</spage><epage>1887</epage><pages>1880-1887</pages><issn>0003-2700</issn><eissn>1520-6882</eissn><abstract>Porous silica is used as a drug delivery agent to improve the bioavailability of sparsely soluble compounds. In this approach, the active pharmaceutical ingredient (API) is commonly loaded into the porous silica by incipient wetness impregnation using organic solvents. Subsequent solvent elimination is critical as the residual solvent concentration cannot exceed threshold values set by health and safety regulations (e.g., EMA/CHMP/ICH/82260/2006). For dichloromethane and methanol, for example, residual concentrations must be below 600 and 3000 ppm, respectively. Today, EU and USA Pharmacopoeias recommend tedious procedures for residual solvent quantification, requiring extraction of the solvent and subsequent quantification using capillary gas chromatography with static headspace sampling (sHS-GC). This work presents a new method based on the combination of standard addition and absolute quantification using magic-angle spinning nuclear magnetic resonance spectroscopy (MAS qNMR). The methodology was originally developed for absolute quantification of water in zeolites and has now been validated for quantification of residual solvent in drug formations using mesoporous silica loaded with ibuprofen dissolved in DCM and MeOH as test samples. Interestingly, formulations prepared using as-received or predried mesoporous silica contained 5465 versus 484.9 ppm DCM, respectively. This implies that the initial water content of the silica carrier can impact the residual solvent concentration in drug-loaded materials. This observation could provide new options to minimize the occurrence of these undesired solvents in the final formulation.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>36579853</pmid><doi>10.1021/acs.analchem.2c03646</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-0274-2759</orcidid><orcidid>https://orcid.org/0000-0003-3499-0455</orcidid><orcidid>https://orcid.org/0000-0003-4074-8833</orcidid><orcidid>https://orcid.org/0000-0002-9292-2357</orcidid></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0003-2700 |
ispartof | Analytical chemistry (Washington), 2023-01, Vol.95 (3), p.1880-1887 |
issn | 0003-2700 1520-6882 |
language | eng |
recordid | cdi_proquest_miscellaneous_2759264632 |
source | ACS Publications |
subjects | Bioavailability Chemistry Dichloromethane Drug delivery Formulations Gas chromatography Headspace Ibuprofen Magnetic resonance spectroscopy Moisture content NMR NMR spectroscopy Nuclear magnetic resonance Nuclear safety Organic solvents Safety regulations Silica Silicon dioxide Solvents Spectroscopy Spectrum analysis Spinning (materials) Water content Zeolites |
title | Absolute Quantification of Residual Solvent in Mesoporous Silica Drug Formulations Using Magic-Angle Spinning NMR Spectroscopy |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T10%3A24%3A39IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Absolute%20Quantification%20of%20Residual%20Solvent%20in%20Mesoporous%20Silica%20Drug%20Formulations%20Using%20Magic-Angle%20Spinning%20NMR%20Spectroscopy&rft.jtitle=Analytical%20chemistry%20(Washington)&rft.au=Vanderschaeghe,%20Hannah&rft.date=2023-01-24&rft.volume=95&rft.issue=3&rft.spage=1880&rft.epage=1887&rft.pages=1880-1887&rft.issn=0003-2700&rft.eissn=1520-6882&rft_id=info:doi/10.1021/acs.analchem.2c03646&rft_dat=%3Cproquest_cross%3E2769621936%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2769621936&rft_id=info:pmid/36579853&rfr_iscdi=true |