Synthesis and enhancing effect of transkarbam 12 on the transdermal delivery of theophylline, clotrimazole, flobufen, and griseofulvin
Dodecyl-6-aminohexanoate (DDEAC) is a transdermal permeation enhancer with excellent activity, low toxicity, and no dermal irritation. We hypothesized that DDEAC reacts with air CO2 to form a two-chain ammonium carbamate--Transkarbam 12 (T12)--which is responsible for the enhancing effect. DDEAC and...
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| Veröffentlicht in: | Pharmaceutical research 2006-05, Vol.23 (5), p.912-919 |
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| creator | HRABALEK, Alexandr DOLEZAL, Pavel VAVROVA, Katerina ZBYTOVSKA, Jarmila HOLAS, Tomas KLIMENTOVA, Jana NOVOTNY, Jakub |
| description | Dodecyl-6-aminohexanoate (DDEAC) is a transdermal permeation enhancer with excellent activity, low toxicity, and no dermal irritation. We hypothesized that DDEAC reacts with air CO2 to form a two-chain ammonium carbamate--Transkarbam 12 (T12)--which is responsible for the enhancing effect.
DDEAC and T12 were synthesized, their structures were confirmed by spectral methods, and their enhancing activity was studied using the Franz diffusion cell and human skin. A high-performance liquid chromatography method was developed for determination of T12, and its biodegradability was evaluated using porcine esterase.
Only the carbamate salt T12 was responsible for the high enhancing activity; DDEAC tested under argon to avoid reaction with CO2 was inactive. T12 enhanced transdermal permeation of drugs covering a wide range of physicochemical properties, including theophylline (enhancement ratio up to 55.6), clotrimazole (7.7), flobufen (5.0), and griseofulvin (24). The activity was pH-dependent, further confirming the importance of the carbamate structure. The metabolization of T12 followed a second-order kinetics with t(1/2) = 31 min.
Our results indicate that T12 is a promising biodegradable permeation enhancer for a wide range of drugs, and the structurally novel group of carbamate enhancers warrants further investigation. |
| doi_str_mv | 10.1007/s11095-006-9782-y |
| format | Article |
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DDEAC and T12 were synthesized, their structures were confirmed by spectral methods, and their enhancing activity was studied using the Franz diffusion cell and human skin. A high-performance liquid chromatography method was developed for determination of T12, and its biodegradability was evaluated using porcine esterase.
Only the carbamate salt T12 was responsible for the high enhancing activity; DDEAC tested under argon to avoid reaction with CO2 was inactive. T12 enhanced transdermal permeation of drugs covering a wide range of physicochemical properties, including theophylline (enhancement ratio up to 55.6), clotrimazole (7.7), flobufen (5.0), and griseofulvin (24). The activity was pH-dependent, further confirming the importance of the carbamate structure. The metabolization of T12 followed a second-order kinetics with t(1/2) = 31 min.
Our results indicate that T12 is a promising biodegradable permeation enhancer for a wide range of drugs, and the structurally novel group of carbamate enhancers warrants further investigation.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1007/s11095-006-9782-y</identifier><identifier>PMID: 16715381</identifier><identifier>CODEN: PHREEB</identifier><language>eng</language><publisher>New York, NY: Springer</publisher><subject>Administration, Cutaneous ; Aged ; Aminocaproates ; Aminocaproic Acid - chemical synthesis ; Aminocaproic Acid - pharmacology ; Biological and medical sciences ; Butyrates - administration & dosage ; Butyrates - metabolism ; Carbamates - chemical synthesis ; Carbamates - pharmacology ; Carbon dioxide ; Chromatography ; Clotrimazole - administration & dosage ; Clotrimazole - metabolism ; Diffusion Chambers, Culture ; Drugs ; Esterases - analysis ; Female ; General pharmacology ; Griseofulvin - administration & dosage ; Griseofulvin - metabolism ; Humans ; Male ; Medical sciences ; Molecular Structure ; NMR ; Nuclear magnetic resonance ; Permeability ; Pharmaceutical technology. Pharmaceutical industry ; Pharmaceuticals ; Pharmacology. Drug treatments ; Pharmacy ; Skin - drug effects ; Skin - metabolism ; Skin Absorption ; Theophylline - administration & dosage ; Theophylline - metabolism ; Toxicity ; Transdermal medication</subject><ispartof>Pharmaceutical research, 2006-05, Vol.23 (5), p.912-919</ispartof><rights>2006 INIST-CNRS</rights><rights>Springer Science + Business Media, Inc. 2006</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-265f63c5636c4f315ddef9b3037ab625bf75be96cde32c614378481b10b7a98a3</citedby><cites>FETCH-LOGICAL-c356t-265f63c5636c4f315ddef9b3037ab625bf75be96cde32c614378481b10b7a98a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17894187$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16715381$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>HRABALEK, Alexandr</creatorcontrib><creatorcontrib>DOLEZAL, Pavel</creatorcontrib><creatorcontrib>VAVROVA, Katerina</creatorcontrib><creatorcontrib>ZBYTOVSKA, Jarmila</creatorcontrib><creatorcontrib>HOLAS, Tomas</creatorcontrib><creatorcontrib>KLIMENTOVA, Jana</creatorcontrib><creatorcontrib>NOVOTNY, Jakub</creatorcontrib><title>Synthesis and enhancing effect of transkarbam 12 on the transdermal delivery of theophylline, clotrimazole, flobufen, and griseofulvin</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><description>Dodecyl-6-aminohexanoate (DDEAC) is a transdermal permeation enhancer with excellent activity, low toxicity, and no dermal irritation. We hypothesized that DDEAC reacts with air CO2 to form a two-chain ammonium carbamate--Transkarbam 12 (T12)--which is responsible for the enhancing effect.
DDEAC and T12 were synthesized, their structures were confirmed by spectral methods, and their enhancing activity was studied using the Franz diffusion cell and human skin. A high-performance liquid chromatography method was developed for determination of T12, and its biodegradability was evaluated using porcine esterase.
Only the carbamate salt T12 was responsible for the high enhancing activity; DDEAC tested under argon to avoid reaction with CO2 was inactive. T12 enhanced transdermal permeation of drugs covering a wide range of physicochemical properties, including theophylline (enhancement ratio up to 55.6), clotrimazole (7.7), flobufen (5.0), and griseofulvin (24). The activity was pH-dependent, further confirming the importance of the carbamate structure. The metabolization of T12 followed a second-order kinetics with t(1/2) = 31 min.
Our results indicate that T12 is a promising biodegradable permeation enhancer for a wide range of drugs, and the structurally novel group of carbamate enhancers warrants further investigation.</description><subject>Administration, Cutaneous</subject><subject>Aged</subject><subject>Aminocaproates</subject><subject>Aminocaproic Acid - chemical synthesis</subject><subject>Aminocaproic Acid - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Butyrates - administration & dosage</subject><subject>Butyrates - metabolism</subject><subject>Carbamates - chemical synthesis</subject><subject>Carbamates - pharmacology</subject><subject>Carbon dioxide</subject><subject>Chromatography</subject><subject>Clotrimazole - administration & dosage</subject><subject>Clotrimazole - metabolism</subject><subject>Diffusion Chambers, Culture</subject><subject>Drugs</subject><subject>Esterases - analysis</subject><subject>Female</subject><subject>General pharmacology</subject><subject>Griseofulvin - administration & dosage</subject><subject>Griseofulvin - metabolism</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Molecular Structure</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Permeability</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmaceuticals</subject><subject>Pharmacology. Drug treatments</subject><subject>Pharmacy</subject><subject>Skin - drug effects</subject><subject>Skin - metabolism</subject><subject>Skin Absorption</subject><subject>Theophylline - administration & dosage</subject><subject>Theophylline - metabolism</subject><subject>Toxicity</subject><subject>Transdermal medication</subject><issn>0724-8741</issn><issn>1573-904X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpFkM-KFDEQh4Mo7uzqA3iRIHjb1lT-91GW1RUWPKjgLSTpZKfXTDIm3QvtA_jc9uwM7Kmo4vtVUR9Cb4B8AELUxwZAetERIrteadotz9AGhGJdT_iv52hDFOWdVhzO0Hlr94QQDT1_ic5AKhBMwwb9-77kaRva2LDNAw55a7Mf8x0OMQY_4RLxVG1uv211doeB4pLxGjhOh1B3NuEhpPEh1OWR3oay3y4pjTlcYp_KVMed_VvS2sVU3BxDvny8dVfHFkqc08OYX6EX0aYWXp_qBfr5-frH1U13--3L16tPt51nQk4dlSJK5oVk0vPIQAxDiL1jhCnrJBUuKuFCL_0QGPUSOFOaa3BAnLK9tuwCvTvu3dfyZw5tMvdlrnk9aSilUkuu2ArBEfK1tFZDNPvDD3UxQMxBvDmKN6t4cxBvljXz9rR4drswPCVOplfg_QmwzdsU68Fze-KU7jloxf4Dq0CNsQ</recordid><startdate>20060501</startdate><enddate>20060501</enddate><creator>HRABALEK, Alexandr</creator><creator>DOLEZAL, Pavel</creator><creator>VAVROVA, Katerina</creator><creator>ZBYTOVSKA, Jarmila</creator><creator>HOLAS, Tomas</creator><creator>KLIMENTOVA, Jana</creator><creator>NOVOTNY, Jakub</creator><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</scope><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>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></search><sort><creationdate>20060501</creationdate><title>Synthesis and enhancing effect of transkarbam 12 on the transdermal delivery of theophylline, clotrimazole, flobufen, and griseofulvin</title><author>HRABALEK, Alexandr ; DOLEZAL, Pavel ; VAVROVA, Katerina ; ZBYTOVSKA, Jarmila ; HOLAS, Tomas ; KLIMENTOVA, Jana ; NOVOTNY, Jakub</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-265f63c5636c4f315ddef9b3037ab625bf75be96cde32c614378481b10b7a98a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Administration, Cutaneous</topic><topic>Aged</topic><topic>Aminocaproates</topic><topic>Aminocaproic Acid - chemical synthesis</topic><topic>Aminocaproic Acid - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Butyrates - administration & dosage</topic><topic>Butyrates - metabolism</topic><topic>Carbamates - chemical synthesis</topic><topic>Carbamates - pharmacology</topic><topic>Carbon dioxide</topic><topic>Chromatography</topic><topic>Clotrimazole - administration & dosage</topic><topic>Clotrimazole - metabolism</topic><topic>Diffusion Chambers, Culture</topic><topic>Drugs</topic><topic>Esterases - analysis</topic><topic>Female</topic><topic>General pharmacology</topic><topic>Griseofulvin - administration & dosage</topic><topic>Griseofulvin - metabolism</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Molecular Structure</topic><topic>NMR</topic><topic>Nuclear magnetic resonance</topic><topic>Permeability</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmaceuticals</topic><topic>Pharmacology. Drug treatments</topic><topic>Pharmacy</topic><topic>Skin - drug effects</topic><topic>Skin - metabolism</topic><topic>Skin Absorption</topic><topic>Theophylline - administration & dosage</topic><topic>Theophylline - metabolism</topic><topic>Toxicity</topic><topic>Transdermal medication</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HRABALEK, Alexandr</creatorcontrib><creatorcontrib>DOLEZAL, Pavel</creatorcontrib><creatorcontrib>VAVROVA, Katerina</creatorcontrib><creatorcontrib>ZBYTOVSKA, Jarmila</creatorcontrib><creatorcontrib>HOLAS, Tomas</creatorcontrib><creatorcontrib>KLIMENTOVA, Jana</creatorcontrib><creatorcontrib>NOVOTNY, Jakub</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>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><jtitle>Pharmaceutical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>HRABALEK, Alexandr</au><au>DOLEZAL, Pavel</au><au>VAVROVA, Katerina</au><au>ZBYTOVSKA, Jarmila</au><au>HOLAS, Tomas</au><au>KLIMENTOVA, Jana</au><au>NOVOTNY, Jakub</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and enhancing effect of transkarbam 12 on the transdermal delivery of theophylline, clotrimazole, flobufen, and griseofulvin</atitle><jtitle>Pharmaceutical research</jtitle><addtitle>Pharm Res</addtitle><date>2006-05-01</date><risdate>2006</risdate><volume>23</volume><issue>5</issue><spage>912</spage><epage>919</epage><pages>912-919</pages><issn>0724-8741</issn><eissn>1573-904X</eissn><coden>PHREEB</coden><abstract>Dodecyl-6-aminohexanoate (DDEAC) is a transdermal permeation enhancer with excellent activity, low toxicity, and no dermal irritation. We hypothesized that DDEAC reacts with air CO2 to form a two-chain ammonium carbamate--Transkarbam 12 (T12)--which is responsible for the enhancing effect.
DDEAC and T12 were synthesized, their structures were confirmed by spectral methods, and their enhancing activity was studied using the Franz diffusion cell and human skin. A high-performance liquid chromatography method was developed for determination of T12, and its biodegradability was evaluated using porcine esterase.
Only the carbamate salt T12 was responsible for the high enhancing activity; DDEAC tested under argon to avoid reaction with CO2 was inactive. T12 enhanced transdermal permeation of drugs covering a wide range of physicochemical properties, including theophylline (enhancement ratio up to 55.6), clotrimazole (7.7), flobufen (5.0), and griseofulvin (24). The activity was pH-dependent, further confirming the importance of the carbamate structure. The metabolization of T12 followed a second-order kinetics with t(1/2) = 31 min.
Our results indicate that T12 is a promising biodegradable permeation enhancer for a wide range of drugs, and the structurally novel group of carbamate enhancers warrants further investigation.</abstract><cop>New York, NY</cop><pub>Springer</pub><pmid>16715381</pmid><doi>10.1007/s11095-006-9782-y</doi><tpages>8</tpages></addata></record> |
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| subjects | Administration, Cutaneous Aged Aminocaproates Aminocaproic Acid - chemical synthesis Aminocaproic Acid - pharmacology Biological and medical sciences Butyrates - administration & dosage Butyrates - metabolism Carbamates - chemical synthesis Carbamates - pharmacology Carbon dioxide Chromatography Clotrimazole - administration & dosage Clotrimazole - metabolism Diffusion Chambers, Culture Drugs Esterases - analysis Female General pharmacology Griseofulvin - administration & dosage Griseofulvin - metabolism Humans Male Medical sciences Molecular Structure NMR Nuclear magnetic resonance Permeability Pharmaceutical technology. Pharmaceutical industry Pharmaceuticals Pharmacology. Drug treatments Pharmacy Skin - drug effects Skin - metabolism Skin Absorption Theophylline - administration & dosage Theophylline - metabolism Toxicity Transdermal medication |
| title | Synthesis and enhancing effect of transkarbam 12 on the transdermal delivery of theophylline, clotrimazole, flobufen, and griseofulvin |
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