Enhancement of nasal delivery of a renin inhibitor in the rat using emulsion formulations
Nasal absorption of O-(N-morpholino-carbonyl-3-L-phenylaspartyl-L-leucinamide of (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane (I), a renin inhibitor, was evaluated in two rat nasal models, one involving surgery and the other requiring no surgical intervention. Oleic acid/monoolein e...
Gespeichert in:
| Veröffentlicht in: | Pharmaceutical research 1992-08, Vol.9 (8), p.1024-1028 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1028 |
|---|---|
| container_issue | 8 |
| container_start_page | 1024 |
| container_title | Pharmaceutical research |
| container_volume | 9 |
| creator | KARARLI, T. T NEEDHAM, T. E SCHOENHARD, G BARON, D. A SCHMIDT, R. E KATZ, B BELONIO, B |
| description | Nasal absorption of O-(N-morpholino-carbonyl-3-L-phenylaspartyl-L-leucinamide of (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane (I), a renin inhibitor, was evaluated in two rat nasal models, one involving surgery and the other requiring no surgical intervention. Oleic acid/monoolein emulsion formulations were tested along with a control PEG 400 solution. The percent absolute bioavailability of the compound was enhanced from 3-6% (PEG 400 solution) to 15-27% when the emulsion formulations were used. The different nasal model techniques (with and without surgery) did not produce any statistical difference in the absolute bioavailability values for I. Emulsion formulations did not produce appreciable damage as assessed morphologically. It is suggested that emulsion formulations containing membrane adjuvants such as oleic acid and monoolein can be used to enhanced the nasal delivery of low-bioavailable, lipid-soluble drugs. |
| doi_str_mv | 10.1023/A:1015850310589 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_73246736</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>73246736</sourcerecordid><originalsourceid>FETCH-LOGICAL-c281t-5c79edffbb9c42434d78c4eb1e848e0ce02d4b10b268145776a7bcbb9a0546ad3</originalsourceid><addsrcrecordid>eNo9kEtLxDAUhYMo4zi6diVkIe6qebVJ3Q3D-IABNwq6Kkl660TadExaYf69GSyu7sc9H2dxELqk5JYSxu-W95TQXOWEU5Kr8gjNaS55VhLxfozmRDKRKSnoKTqL8YsQomgpZmhGBSm5ZHP0sfZb7S104AfcN9jrqFtcQ-t-IOwPH40DeOex81tn3NCHRHjYAg56wGN0_hNDN7bR9R43fUioh8TxHJ00uo1wMd0FentYv66ess3L4_NqucksU3TIcitLqJvGmNIKJriopbICDAUlFBALhNXCUGJYoajIpSy0NDbZmuSi0DVfoJu_3l3ov0eIQ9W5aKFttYd-jJXkTBSSF0m8msTRdFBXu-A6HfbVtEXKr6dcR6vbJqRdXPzX8rTrwfwFj-9uXg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>73246736</pqid></control><display><type>article</type><title>Enhancement of nasal delivery of a renin inhibitor in the rat using emulsion formulations</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>KARARLI, T. T ; NEEDHAM, T. E ; SCHOENHARD, G ; BARON, D. A ; SCHMIDT, R. E ; KATZ, B ; BELONIO, B</creator><creatorcontrib>KARARLI, T. T ; NEEDHAM, T. E ; SCHOENHARD, G ; BARON, D. A ; SCHMIDT, R. E ; KATZ, B ; BELONIO, B</creatorcontrib><description>Nasal absorption of O-(N-morpholino-carbonyl-3-L-phenylaspartyl-L-leucinamide of (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane (I), a renin inhibitor, was evaluated in two rat nasal models, one involving surgery and the other requiring no surgical intervention. Oleic acid/monoolein emulsion formulations were tested along with a control PEG 400 solution. The percent absolute bioavailability of the compound was enhanced from 3-6% (PEG 400 solution) to 15-27% when the emulsion formulations were used. The different nasal model techniques (with and without surgery) did not produce any statistical difference in the absolute bioavailability values for I. Emulsion formulations did not produce appreciable damage as assessed morphologically. It is suggested that emulsion formulations containing membrane adjuvants such as oleic acid and monoolein can be used to enhanced the nasal delivery of low-bioavailable, lipid-soluble drugs.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1023/A:1015850310589</identifier><identifier>PMID: 1409372</identifier><identifier>CODEN: PHREEB</identifier><language>eng</language><publisher>New York, NY: Springer</publisher><subject>Administration, Intranasal ; Animals ; Biological and medical sciences ; Biological Availability ; Chromatography, High Pressure Liquid ; Dipeptides - administration & dosage ; Dipeptides - pharmacokinetics ; Emulsions ; General pharmacology ; Glycerides - chemistry ; Male ; Medical sciences ; Morpholines - administration & dosage ; Morpholines - pharmacokinetics ; Nasal Mucosa - drug effects ; Oleic Acid ; Oleic Acids - chemistry ; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions ; Pharmacology. Drug treatments ; Rats ; Rats, Sprague-Dawley ; Renin - antagonists & inhibitors ; Solubility ; Taurocholic Acid - chemistry</subject><ispartof>Pharmaceutical research, 1992-08, Vol.9 (8), p.1024-1028</ispartof><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c281t-5c79edffbb9c42434d78c4eb1e848e0ce02d4b10b268145776a7bcbb9a0546ad3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5573409$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1409372$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KARARLI, T. T</creatorcontrib><creatorcontrib>NEEDHAM, T. E</creatorcontrib><creatorcontrib>SCHOENHARD, G</creatorcontrib><creatorcontrib>BARON, D. A</creatorcontrib><creatorcontrib>SCHMIDT, R. E</creatorcontrib><creatorcontrib>KATZ, B</creatorcontrib><creatorcontrib>BELONIO, B</creatorcontrib><title>Enhancement of nasal delivery of a renin inhibitor in the rat using emulsion formulations</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><description>Nasal absorption of O-(N-morpholino-carbonyl-3-L-phenylaspartyl-L-leucinamide of (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane (I), a renin inhibitor, was evaluated in two rat nasal models, one involving surgery and the other requiring no surgical intervention. Oleic acid/monoolein emulsion formulations were tested along with a control PEG 400 solution. The percent absolute bioavailability of the compound was enhanced from 3-6% (PEG 400 solution) to 15-27% when the emulsion formulations were used. The different nasal model techniques (with and without surgery) did not produce any statistical difference in the absolute bioavailability values for I. Emulsion formulations did not produce appreciable damage as assessed morphologically. It is suggested that emulsion formulations containing membrane adjuvants such as oleic acid and monoolein can be used to enhanced the nasal delivery of low-bioavailable, lipid-soluble drugs.</description><subject>Administration, Intranasal</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biological Availability</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Dipeptides - administration & dosage</subject><subject>Dipeptides - pharmacokinetics</subject><subject>Emulsions</subject><subject>General pharmacology</subject><subject>Glycerides - chemistry</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Morpholines - administration & dosage</subject><subject>Morpholines - pharmacokinetics</subject><subject>Nasal Mucosa - drug effects</subject><subject>Oleic Acid</subject><subject>Oleic Acids - chemistry</subject><subject>Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Renin - antagonists & inhibitors</subject><subject>Solubility</subject><subject>Taurocholic Acid - chemistry</subject><issn>0724-8741</issn><issn>1573-904X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kEtLxDAUhYMo4zi6diVkIe6qebVJ3Q3D-IABNwq6Kkl660TadExaYf69GSyu7sc9H2dxELqk5JYSxu-W95TQXOWEU5Kr8gjNaS55VhLxfozmRDKRKSnoKTqL8YsQomgpZmhGBSm5ZHP0sfZb7S104AfcN9jrqFtcQ-t-IOwPH40DeOex81tn3NCHRHjYAg56wGN0_hNDN7bR9R43fUioh8TxHJ00uo1wMd0FentYv66ess3L4_NqucksU3TIcitLqJvGmNIKJriopbICDAUlFBALhNXCUGJYoajIpSy0NDbZmuSi0DVfoJu_3l3ov0eIQ9W5aKFttYd-jJXkTBSSF0m8msTRdFBXu-A6HfbVtEXKr6dcR6vbJqRdXPzX8rTrwfwFj-9uXg</recordid><startdate>19920801</startdate><enddate>19920801</enddate><creator>KARARLI, T. T</creator><creator>NEEDHAM, T. E</creator><creator>SCHOENHARD, G</creator><creator>BARON, D. A</creator><creator>SCHMIDT, R. E</creator><creator>KATZ, B</creator><creator>BELONIO, B</creator><general>Springer</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>19920801</creationdate><title>Enhancement of nasal delivery of a renin inhibitor in the rat using emulsion formulations</title><author>KARARLI, T. T ; NEEDHAM, T. E ; SCHOENHARD, G ; BARON, D. A ; SCHMIDT, R. E ; KATZ, B ; BELONIO, B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c281t-5c79edffbb9c42434d78c4eb1e848e0ce02d4b10b268145776a7bcbb9a0546ad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1992</creationdate><topic>Administration, Intranasal</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biological Availability</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Dipeptides - administration & dosage</topic><topic>Dipeptides - pharmacokinetics</topic><topic>Emulsions</topic><topic>General pharmacology</topic><topic>Glycerides - chemistry</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Morpholines - administration & dosage</topic><topic>Morpholines - pharmacokinetics</topic><topic>Nasal Mucosa - drug effects</topic><topic>Oleic Acid</topic><topic>Oleic Acids - chemistry</topic><topic>Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Renin - antagonists & inhibitors</topic><topic>Solubility</topic><topic>Taurocholic Acid - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KARARLI, T. T</creatorcontrib><creatorcontrib>NEEDHAM, T. E</creatorcontrib><creatorcontrib>SCHOENHARD, G</creatorcontrib><creatorcontrib>BARON, D. A</creatorcontrib><creatorcontrib>SCHMIDT, R. E</creatorcontrib><creatorcontrib>KATZ, B</creatorcontrib><creatorcontrib>BELONIO, B</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Pharmaceutical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>KARARLI, T. T</au><au>NEEDHAM, T. E</au><au>SCHOENHARD, G</au><au>BARON, D. A</au><au>SCHMIDT, R. E</au><au>KATZ, B</au><au>BELONIO, B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Enhancement of nasal delivery of a renin inhibitor in the rat using emulsion formulations</atitle><jtitle>Pharmaceutical research</jtitle><addtitle>Pharm Res</addtitle><date>1992-08-01</date><risdate>1992</risdate><volume>9</volume><issue>8</issue><spage>1024</spage><epage>1028</epage><pages>1024-1028</pages><issn>0724-8741</issn><eissn>1573-904X</eissn><coden>PHREEB</coden><abstract>Nasal absorption of O-(N-morpholino-carbonyl-3-L-phenylaspartyl-L-leucinamide of (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane (I), a renin inhibitor, was evaluated in two rat nasal models, one involving surgery and the other requiring no surgical intervention. Oleic acid/monoolein emulsion formulations were tested along with a control PEG 400 solution. The percent absolute bioavailability of the compound was enhanced from 3-6% (PEG 400 solution) to 15-27% when the emulsion formulations were used. The different nasal model techniques (with and without surgery) did not produce any statistical difference in the absolute bioavailability values for I. Emulsion formulations did not produce appreciable damage as assessed morphologically. It is suggested that emulsion formulations containing membrane adjuvants such as oleic acid and monoolein can be used to enhanced the nasal delivery of low-bioavailable, lipid-soluble drugs.</abstract><cop>New York, NY</cop><pub>Springer</pub><pmid>1409372</pmid><doi>10.1023/A:1015850310589</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0724-8741 |
| ispartof | Pharmaceutical research, 1992-08, Vol.9 (8), p.1024-1028 |
| issn | 0724-8741 1573-904X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_73246736 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Administration, Intranasal Animals Biological and medical sciences Biological Availability Chromatography, High Pressure Liquid Dipeptides - administration & dosage Dipeptides - pharmacokinetics Emulsions General pharmacology Glycerides - chemistry Male Medical sciences Morpholines - administration & dosage Morpholines - pharmacokinetics Nasal Mucosa - drug effects Oleic Acid Oleic Acids - chemistry Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions Pharmacology. Drug treatments Rats Rats, Sprague-Dawley Renin - antagonists & inhibitors Solubility Taurocholic Acid - chemistry |
| title | Enhancement of nasal delivery of a renin inhibitor in the rat using emulsion formulations |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-23T16%3A04%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Enhancement%20of%20nasal%20delivery%20of%20a%20renin%20inhibitor%20in%20the%20rat%20using%20emulsion%20formulations&rft.jtitle=Pharmaceutical%20research&rft.au=KARARLI,%20T.%20T&rft.date=1992-08-01&rft.volume=9&rft.issue=8&rft.spage=1024&rft.epage=1028&rft.pages=1024-1028&rft.issn=0724-8741&rft.eissn=1573-904X&rft.coden=PHREEB&rft_id=info:doi/10.1023/A:1015850310589&rft_dat=%3Cproquest_pubme%3E73246736%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=73246736&rft_id=info:pmid/1409372&rfr_iscdi=true |