Exploring drug solubility in fasted human intestinal fluid aspirates: Impact of inter-individual variability, sampling site and dilution
[Display omitted] One of the main factors defining intestinal drug absorption is the solubility of the compound in the gastrointestinal environment. This study reports the solubility of a series of 27 commonly used acidic, neutral and basic drugs in human intestinal fluid samples collected from the...
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| Veröffentlicht in: | International journal of pharmaceutics 2017-08, Vol.528 (1-2), p.471-484 |
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| container_title | International journal of pharmaceutics |
| container_volume | 528 |
| creator | de la Cruz-Moreno, Mariangeles Pérez Montejo, Consuelo Aguilar-Ros, Antonio Dewe, Walthère Beck, Benoît Stappaerts, Jef Tack, Jan Augustijns, Patrick |
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One of the main factors defining intestinal drug absorption is the solubility of the compound in the gastrointestinal environment. This study reports the solubility of a series of 27 commonly used acidic, neutral and basic drugs in human intestinal fluid samples collected from the duodenum or jejunum of healthy volunteers under fasted state conditions. The interindividual variability as well as the impact of factors such as pH, sampling site and bile salts on the solubility in human intestinal fluids was investigated. The solubility measurements were evaluated using a statistical experimental design. Variability in solubility across volunteers and sampling sites was highly compound-specific and appeared to be substantial for weak acids and bases and for lipophilic drugs. Both pH of the samples and the abundance of amphiphilic components were responsible for the variability observed in the solubility values obtained. The results confirm strong interindividual differences in intraluminal solubility, especially for compounds with high lipophilicity and/or compounds with a pKa value within the physiological pH range. It is important to recognize this variability in intestinal drug solubility as it may considerably influence the therapeutic outcome among patients. |
| doi_str_mv | 10.1016/j.ijpharm.2017.05.072 |
| format | Article |
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One of the main factors defining intestinal drug absorption is the solubility of the compound in the gastrointestinal environment. This study reports the solubility of a series of 27 commonly used acidic, neutral and basic drugs in human intestinal fluid samples collected from the duodenum or jejunum of healthy volunteers under fasted state conditions. The interindividual variability as well as the impact of factors such as pH, sampling site and bile salts on the solubility in human intestinal fluids was investigated. The solubility measurements were evaluated using a statistical experimental design. Variability in solubility across volunteers and sampling sites was highly compound-specific and appeared to be substantial for weak acids and bases and for lipophilic drugs. Both pH of the samples and the abundance of amphiphilic components were responsible for the variability observed in the solubility values obtained. The results confirm strong interindividual differences in intraluminal solubility, especially for compounds with high lipophilicity and/or compounds with a pKa value within the physiological pH range. It is important to recognize this variability in intestinal drug solubility as it may considerably influence the therapeutic outcome among patients.</description><identifier>ISSN: 0378-5173</identifier><identifier>EISSN: 1873-3476</identifier><identifier>DOI: 10.1016/j.ijpharm.2017.05.072</identifier><identifier>PMID: 28591618</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Biological Variation, Individual ; Biorelevant media ; Biorelevant solubility ; Body Fluids ; Drug solubility ; Duodenal solubility ; Duodenum ; Fasting ; Human intestinal fluids ; Humans ; Hydrogen-Ion Concentration ; Intestinal Absorption ; Jejunal solubility ; Jejunum ; Oral absorption ; Pharmaceutical Preparations - chemistry ; Solubility</subject><ispartof>International journal of pharmaceutics, 2017-08, Vol.528 (1-2), p.471-484</ispartof><rights>2017 Elsevier B.V.</rights><rights>Copyright © 2017 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-3a97a15629b9aaf8212e876d2827d662c875940a3057e2f182daadabf4dd6ac43</citedby><cites>FETCH-LOGICAL-c365t-3a97a15629b9aaf8212e876d2827d662c875940a3057e2f182daadabf4dd6ac43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ijpharm.2017.05.072$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28591618$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>de la Cruz-Moreno, Mariangeles Pérez</creatorcontrib><creatorcontrib>Montejo, Consuelo</creatorcontrib><creatorcontrib>Aguilar-Ros, Antonio</creatorcontrib><creatorcontrib>Dewe, Walthère</creatorcontrib><creatorcontrib>Beck, Benoît</creatorcontrib><creatorcontrib>Stappaerts, Jef</creatorcontrib><creatorcontrib>Tack, Jan</creatorcontrib><creatorcontrib>Augustijns, Patrick</creatorcontrib><title>Exploring drug solubility in fasted human intestinal fluid aspirates: Impact of inter-individual variability, sampling site and dilution</title><title>International journal of pharmaceutics</title><addtitle>Int J Pharm</addtitle><description>[Display omitted]
One of the main factors defining intestinal drug absorption is the solubility of the compound in the gastrointestinal environment. This study reports the solubility of a series of 27 commonly used acidic, neutral and basic drugs in human intestinal fluid samples collected from the duodenum or jejunum of healthy volunteers under fasted state conditions. The interindividual variability as well as the impact of factors such as pH, sampling site and bile salts on the solubility in human intestinal fluids was investigated. The solubility measurements were evaluated using a statistical experimental design. Variability in solubility across volunteers and sampling sites was highly compound-specific and appeared to be substantial for weak acids and bases and for lipophilic drugs. Both pH of the samples and the abundance of amphiphilic components were responsible for the variability observed in the solubility values obtained. The results confirm strong interindividual differences in intraluminal solubility, especially for compounds with high lipophilicity and/or compounds with a pKa value within the physiological pH range. It is important to recognize this variability in intestinal drug solubility as it may considerably influence the therapeutic outcome among patients.</description><subject>Biological Variation, Individual</subject><subject>Biorelevant media</subject><subject>Biorelevant solubility</subject><subject>Body Fluids</subject><subject>Drug solubility</subject><subject>Duodenal solubility</subject><subject>Duodenum</subject><subject>Fasting</subject><subject>Human intestinal fluids</subject><subject>Humans</subject><subject>Hydrogen-Ion Concentration</subject><subject>Intestinal Absorption</subject><subject>Jejunal solubility</subject><subject>Jejunum</subject><subject>Oral absorption</subject><subject>Pharmaceutical Preparations - chemistry</subject><subject>Solubility</subject><issn>0378-5173</issn><issn>1873-3476</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctuFDEQRS0EIkPgE0BesqAbP8aPZoOiKECkSGxgbdXY7qRG7gd294j8AZ-NhxnYsipV6VRd3bqEvOas5Yzr9_sW9_MD5KEVjJuWqZYZ8YRsuDWykVujn5INk8Y2iht5QV6UsmeMacHlc3IhrOq45nZDft38nNOUcbynIa_3tExp3WHC5ZHiSHsoSwz0YR1grP0Sy4IjJNqnFQOFMmOGOvxAb4cZ_EKn_g-VGxwDHjCslT1ARjidfEcLDHM6ihVcIoUx0IBpXXAaX5JnPaQSX53rJfn-6ebb9Zfm7uvn2-uru8ZLrZZGQmeAKy26XQfQW8FFtEYHYYUJWgtvjeq2DCRTJoqeWxEAAuz6bQga_FZekrenu3OefqzVkBuw-JgSjHFai-MdM1JIa7qKqhPq81RKjr2bMw6QHx1n7hiC27tzCO4YgmPK1RDq3puzxLobYvi39ffrFfh4AmI1esCYXfEYRx8D5ugXFyb8j8Rvo52eeA</recordid><startdate>20170807</startdate><enddate>20170807</enddate><creator>de la Cruz-Moreno, Mariangeles Pérez</creator><creator>Montejo, Consuelo</creator><creator>Aguilar-Ros, Antonio</creator><creator>Dewe, Walthère</creator><creator>Beck, Benoît</creator><creator>Stappaerts, Jef</creator><creator>Tack, Jan</creator><creator>Augustijns, Patrick</creator><general>Elsevier B.V</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>7X8</scope></search><sort><creationdate>20170807</creationdate><title>Exploring drug solubility in fasted human intestinal fluid aspirates: Impact of inter-individual variability, sampling site and dilution</title><author>de la Cruz-Moreno, Mariangeles Pérez ; Montejo, Consuelo ; Aguilar-Ros, Antonio ; Dewe, Walthère ; Beck, Benoît ; Stappaerts, Jef ; Tack, Jan ; Augustijns, Patrick</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-3a97a15629b9aaf8212e876d2827d662c875940a3057e2f182daadabf4dd6ac43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Biological Variation, Individual</topic><topic>Biorelevant media</topic><topic>Biorelevant solubility</topic><topic>Body Fluids</topic><topic>Drug solubility</topic><topic>Duodenal solubility</topic><topic>Duodenum</topic><topic>Fasting</topic><topic>Human intestinal fluids</topic><topic>Humans</topic><topic>Hydrogen-Ion Concentration</topic><topic>Intestinal Absorption</topic><topic>Jejunal solubility</topic><topic>Jejunum</topic><topic>Oral absorption</topic><topic>Pharmaceutical Preparations - chemistry</topic><topic>Solubility</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>de la Cruz-Moreno, Mariangeles Pérez</creatorcontrib><creatorcontrib>Montejo, Consuelo</creatorcontrib><creatorcontrib>Aguilar-Ros, Antonio</creatorcontrib><creatorcontrib>Dewe, Walthère</creatorcontrib><creatorcontrib>Beck, Benoît</creatorcontrib><creatorcontrib>Stappaerts, Jef</creatorcontrib><creatorcontrib>Tack, Jan</creatorcontrib><creatorcontrib>Augustijns, Patrick</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of pharmaceutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>de la Cruz-Moreno, Mariangeles Pérez</au><au>Montejo, Consuelo</au><au>Aguilar-Ros, Antonio</au><au>Dewe, Walthère</au><au>Beck, Benoît</au><au>Stappaerts, Jef</au><au>Tack, Jan</au><au>Augustijns, Patrick</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exploring drug solubility in fasted human intestinal fluid aspirates: Impact of inter-individual variability, sampling site and dilution</atitle><jtitle>International journal of pharmaceutics</jtitle><addtitle>Int J Pharm</addtitle><date>2017-08-07</date><risdate>2017</risdate><volume>528</volume><issue>1-2</issue><spage>471</spage><epage>484</epage><pages>471-484</pages><issn>0378-5173</issn><eissn>1873-3476</eissn><abstract>[Display omitted]
One of the main factors defining intestinal drug absorption is the solubility of the compound in the gastrointestinal environment. This study reports the solubility of a series of 27 commonly used acidic, neutral and basic drugs in human intestinal fluid samples collected from the duodenum or jejunum of healthy volunteers under fasted state conditions. The interindividual variability as well as the impact of factors such as pH, sampling site and bile salts on the solubility in human intestinal fluids was investigated. The solubility measurements were evaluated using a statistical experimental design. Variability in solubility across volunteers and sampling sites was highly compound-specific and appeared to be substantial for weak acids and bases and for lipophilic drugs. Both pH of the samples and the abundance of amphiphilic components were responsible for the variability observed in the solubility values obtained. The results confirm strong interindividual differences in intraluminal solubility, especially for compounds with high lipophilicity and/or compounds with a pKa value within the physiological pH range. It is important to recognize this variability in intestinal drug solubility as it may considerably influence the therapeutic outcome among patients.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>28591618</pmid><doi>10.1016/j.ijpharm.2017.05.072</doi><tpages>14</tpages></addata></record> |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Biological Variation, Individual Biorelevant media Biorelevant solubility Body Fluids Drug solubility Duodenal solubility Duodenum Fasting Human intestinal fluids Humans Hydrogen-Ion Concentration Intestinal Absorption Jejunal solubility Jejunum Oral absorption Pharmaceutical Preparations - chemistry Solubility |
| title | Exploring drug solubility in fasted human intestinal fluid aspirates: Impact of inter-individual variability, sampling site and dilution |
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