The Co‐Crystal Approach to Improve the Exposure of a Water‐Insoluble Compound: AMG 517 Sorbic Acid Co‐Crystal Characterization and Pharmacokinetics
Co‐crystals are relatively novel in the pharmaceutical field and are not reported extensively. AMG 517 is an insoluble small molecule VR1 (vanilloid receptor 1) antagonist. In animal studies, good exposure of AMG 517 is seen from a 10% (w/v) Pluronic® F108 in OraPlus® suspension. Investigation of th...
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| Veröffentlicht in: | Journal of pharmaceutical sciences 2008-09, Vol.97 (9), p.3942-3956 |
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| creator | Bak, Annette Gore, Anu Yanez, Evelyn Stanton, Mary Tufekcic, Sunita Syed, Rashid Akrami, Anna Rose, Mark Surapaneni, Sekhar Bostick, Tracy King, Anthony Neervannan, Sesha Ostovic, Drazen Koparkar, Arun |
| description | Co‐crystals are relatively novel in the pharmaceutical field and are not reported extensively. AMG 517 is an insoluble small molecule VR1 (vanilloid receptor 1) antagonist. In animal studies, good exposure of AMG 517 is seen from a 10% (w/v) Pluronic® F108 in OraPlus® suspension. Investigation of the suspension formulation revealed that AMG 517 forms a co‐crystal with sorbic acid, a preservative in OraPlus®. This co‐crystal of AMG 517 was isolated by coslurrying AMG 517 and sorbic acid; studied by DSC and XRD; and identified by solution NMR, TGA, and HPLC to be a 1:1 association of AMG 517 and sorbic acid. Single crystal structure analysis revealed a 1:1 co‐crystal of AMG 517 and sorbic acid, held together by two hydrogen bonds and other noncovalent, nonionic forces. The co‐crystal has better aqueous solubility initially as compared to AMG 517 free base but does revert back to a form of the free base hydrate during prolonged slurry in FaSIF (fasted simulated intestinal fluid). Pharmacokinetic evaluation of the co‐crystal in rats using 10% (w/v) Pluronic F108® in OraPlus® suspensions revealed that a 30 mg/kg dose in suspension had comparable exposure to a 500 mg/kg dose of the free base. © 2008 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:3942–3956, 2008 |
| doi_str_mv | 10.1002/jps.21280 |
| format | Article |
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AMG 517 is an insoluble small molecule VR1 (vanilloid receptor 1) antagonist. In animal studies, good exposure of AMG 517 is seen from a 10% (w/v) Pluronic® F108 in OraPlus® suspension. Investigation of the suspension formulation revealed that AMG 517 forms a co‐crystal with sorbic acid, a preservative in OraPlus®. This co‐crystal of AMG 517 was isolated by coslurrying AMG 517 and sorbic acid; studied by DSC and XRD; and identified by solution NMR, TGA, and HPLC to be a 1:1 association of AMG 517 and sorbic acid. Single crystal structure analysis revealed a 1:1 co‐crystal of AMG 517 and sorbic acid, held together by two hydrogen bonds and other noncovalent, nonionic forces. The co‐crystal has better aqueous solubility initially as compared to AMG 517 free base but does revert back to a form of the free base hydrate during prolonged slurry in FaSIF (fasted simulated intestinal fluid). Pharmacokinetic evaluation of the co‐crystal in rats using 10% (w/v) Pluronic F108® in OraPlus® suspensions revealed that a 30 mg/kg dose in suspension had comparable exposure to a 500 mg/kg dose of the free base. © 2008 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:3942–3956, 2008</description><identifier>ISSN: 0022-3549</identifier><identifier>EISSN: 1520-6017</identifier><identifier>DOI: 10.1002/jps.21280</identifier><identifier>PMID: 18214948</identifier><identifier>CODEN: JPMSAE</identifier><language>eng</language><publisher>Hoboken: Elsevier Inc</publisher><subject>Animals ; Benzothiazoles - blood ; Benzothiazoles - chemistry ; Benzothiazoles - pharmacokinetics ; bioavailability ; Biological and medical sciences ; Chromatography, High Pressure Liquid ; co-crystals ; Crystallization ; Crystallography, X-Ray ; General pharmacology ; Magnetic Resonance Spectroscopy ; Medical sciences ; Particle Size ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; physical characterization ; physical stability ; physicochemical properties ; Pyrimidines - blood ; Pyrimidines - chemistry ; Pyrimidines - pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Solubility ; TRPV Cation Channels - antagonists & inhibitors ; Water - chemistry</subject><ispartof>Journal of pharmaceutical sciences, 2008-09, Vol.97 (9), p.3942-3956</ispartof><rights>2008 Wiley-Liss, Inc.</rights><rights>Copyright © 2008 Wiley‐Liss, Inc.</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4310-2c39f0e7499bf37dd890d08384c261982a876c044886fd037c178e9a30957b583</citedby><cites>FETCH-LOGICAL-c4310-2c39f0e7499bf37dd890d08384c261982a876c044886fd037c178e9a30957b583</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjps.21280$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjps.21280$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20632226$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18214948$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bak, Annette</creatorcontrib><creatorcontrib>Gore, Anu</creatorcontrib><creatorcontrib>Yanez, Evelyn</creatorcontrib><creatorcontrib>Stanton, Mary</creatorcontrib><creatorcontrib>Tufekcic, Sunita</creatorcontrib><creatorcontrib>Syed, Rashid</creatorcontrib><creatorcontrib>Akrami, Anna</creatorcontrib><creatorcontrib>Rose, Mark</creatorcontrib><creatorcontrib>Surapaneni, Sekhar</creatorcontrib><creatorcontrib>Bostick, Tracy</creatorcontrib><creatorcontrib>King, Anthony</creatorcontrib><creatorcontrib>Neervannan, Sesha</creatorcontrib><creatorcontrib>Ostovic, Drazen</creatorcontrib><creatorcontrib>Koparkar, Arun</creatorcontrib><title>The Co‐Crystal Approach to Improve the Exposure of a Water‐Insoluble Compound: AMG 517 Sorbic Acid Co‐Crystal Characterization and Pharmacokinetics</title><title>Journal of pharmaceutical sciences</title><addtitle>J. Pharm. Sci</addtitle><description>Co‐crystals are relatively novel in the pharmaceutical field and are not reported extensively. AMG 517 is an insoluble small molecule VR1 (vanilloid receptor 1) antagonist. In animal studies, good exposure of AMG 517 is seen from a 10% (w/v) Pluronic® F108 in OraPlus® suspension. Investigation of the suspension formulation revealed that AMG 517 forms a co‐crystal with sorbic acid, a preservative in OraPlus®. This co‐crystal of AMG 517 was isolated by coslurrying AMG 517 and sorbic acid; studied by DSC and XRD; and identified by solution NMR, TGA, and HPLC to be a 1:1 association of AMG 517 and sorbic acid. Single crystal structure analysis revealed a 1:1 co‐crystal of AMG 517 and sorbic acid, held together by two hydrogen bonds and other noncovalent, nonionic forces. The co‐crystal has better aqueous solubility initially as compared to AMG 517 free base but does revert back to a form of the free base hydrate during prolonged slurry in FaSIF (fasted simulated intestinal fluid). Pharmacokinetic evaluation of the co‐crystal in rats using 10% (w/v) Pluronic F108® in OraPlus® suspensions revealed that a 30 mg/kg dose in suspension had comparable exposure to a 500 mg/kg dose of the free base. © 2008 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:3942–3956, 2008</description><subject>Animals</subject><subject>Benzothiazoles - blood</subject><subject>Benzothiazoles - chemistry</subject><subject>Benzothiazoles - pharmacokinetics</subject><subject>bioavailability</subject><subject>Biological and medical sciences</subject><subject>Chromatography, High Pressure Liquid</subject><subject>co-crystals</subject><subject>Crystallization</subject><subject>Crystallography, X-Ray</subject><subject>General pharmacology</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Medical sciences</subject><subject>Particle Size</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>physical characterization</subject><subject>physical stability</subject><subject>physicochemical properties</subject><subject>Pyrimidines - blood</subject><subject>Pyrimidines - chemistry</subject><subject>Pyrimidines - pharmacokinetics</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Solubility</subject><subject>TRPV Cation Channels - antagonists & inhibitors</subject><subject>Water - chemistry</subject><issn>0022-3549</issn><issn>1520-6017</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1u1DAUhS0EokNhwQsgb0BikdY_SWyzG6XtMKjASB1UdpbjOBq3SRzspO10xSOw5fV4ElwyFCHBypb9nXN07wHgOUYHGCFyeNGHA4IJRw_ADGcEJTnC7CGYxT-S0CwVe-BJCBcIoRxl2WOwhznBqUj5DHxfbwws3I-v3wq_DYNq4LzvvVN6AwcHl228Xxk4ROj4pndh9Aa6Gip4rgbjo2rZBdeMZXNn0vZu7Ko3cP5-ATPM4JnzpdVwrm31d0SxUV7paGBv1WBdB1VXwVV8bJV2l7Yzg9XhKXhUqyaYZ7tzH3w6OV4Xb5PTj4tlMT9NdEoxSoimokaGpUKUNWVVxQWqEKc81STHghPFWa5RmnKe1xWiTGPGjVAUiYyVGaf74NXkG0f9MpowyNYGbZpGdcaNQeaCCso5jeDrCdTeheBNLXtvW-W3EiN514OMPchfPUT2xc50LFtT_SF3i4_Ayx2gglZN7VWnbbjnCMopISSP3OHEXdvGbP-fKN-tzn5HJ5PChsHc3CuUv5Q5oyyT5x8WMj85Qnz9eSWPIk8n3sQlX1njZdDWdNpU1hs9yMrZfwz4EyB4weo</recordid><startdate>200809</startdate><enddate>200809</enddate><creator>Bak, Annette</creator><creator>Gore, Anu</creator><creator>Yanez, Evelyn</creator><creator>Stanton, Mary</creator><creator>Tufekcic, Sunita</creator><creator>Syed, Rashid</creator><creator>Akrami, Anna</creator><creator>Rose, Mark</creator><creator>Surapaneni, Sekhar</creator><creator>Bostick, Tracy</creator><creator>King, Anthony</creator><creator>Neervannan, Sesha</creator><creator>Ostovic, Drazen</creator><creator>Koparkar, Arun</creator><general>Elsevier Inc</general><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley</general><general>American Pharmaceutical Association</general><scope>BSCLL</scope><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>7X8</scope></search><sort><creationdate>200809</creationdate><title>The Co‐Crystal Approach to Improve the Exposure of a Water‐Insoluble Compound: AMG 517 Sorbic Acid Co‐Crystal Characterization and Pharmacokinetics</title><author>Bak, Annette ; Gore, Anu ; Yanez, Evelyn ; Stanton, Mary ; Tufekcic, Sunita ; Syed, Rashid ; Akrami, Anna ; Rose, Mark ; Surapaneni, Sekhar ; Bostick, Tracy ; King, Anthony ; Neervannan, Sesha ; Ostovic, Drazen ; Koparkar, Arun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4310-2c39f0e7499bf37dd890d08384c261982a876c044886fd037c178e9a30957b583</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Benzothiazoles - blood</topic><topic>Benzothiazoles - chemistry</topic><topic>Benzothiazoles - pharmacokinetics</topic><topic>bioavailability</topic><topic>Biological and medical sciences</topic><topic>Chromatography, High Pressure Liquid</topic><topic>co-crystals</topic><topic>Crystallization</topic><topic>Crystallography, X-Ray</topic><topic>General pharmacology</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Medical sciences</topic><topic>Particle Size</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>physical characterization</topic><topic>physical stability</topic><topic>physicochemical properties</topic><topic>Pyrimidines - blood</topic><topic>Pyrimidines - chemistry</topic><topic>Pyrimidines - pharmacokinetics</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Solubility</topic><topic>TRPV Cation Channels - antagonists & inhibitors</topic><topic>Water - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bak, Annette</creatorcontrib><creatorcontrib>Gore, Anu</creatorcontrib><creatorcontrib>Yanez, Evelyn</creatorcontrib><creatorcontrib>Stanton, Mary</creatorcontrib><creatorcontrib>Tufekcic, Sunita</creatorcontrib><creatorcontrib>Syed, Rashid</creatorcontrib><creatorcontrib>Akrami, Anna</creatorcontrib><creatorcontrib>Rose, Mark</creatorcontrib><creatorcontrib>Surapaneni, Sekhar</creatorcontrib><creatorcontrib>Bostick, Tracy</creatorcontrib><creatorcontrib>King, Anthony</creatorcontrib><creatorcontrib>Neervannan, Sesha</creatorcontrib><creatorcontrib>Ostovic, Drazen</creatorcontrib><creatorcontrib>Koparkar, Arun</creatorcontrib><collection>Istex</collection><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>MEDLINE - Academic</collection><jtitle>Journal of pharmaceutical sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bak, Annette</au><au>Gore, Anu</au><au>Yanez, Evelyn</au><au>Stanton, Mary</au><au>Tufekcic, Sunita</au><au>Syed, Rashid</au><au>Akrami, Anna</au><au>Rose, Mark</au><au>Surapaneni, Sekhar</au><au>Bostick, Tracy</au><au>King, Anthony</au><au>Neervannan, Sesha</au><au>Ostovic, Drazen</au><au>Koparkar, Arun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Co‐Crystal Approach to Improve the Exposure of a Water‐Insoluble Compound: AMG 517 Sorbic Acid Co‐Crystal Characterization and Pharmacokinetics</atitle><jtitle>Journal of pharmaceutical sciences</jtitle><addtitle>J. Pharm. Sci</addtitle><date>2008-09</date><risdate>2008</risdate><volume>97</volume><issue>9</issue><spage>3942</spage><epage>3956</epage><pages>3942-3956</pages><issn>0022-3549</issn><eissn>1520-6017</eissn><coden>JPMSAE</coden><abstract>Co‐crystals are relatively novel in the pharmaceutical field and are not reported extensively. AMG 517 is an insoluble small molecule VR1 (vanilloid receptor 1) antagonist. In animal studies, good exposure of AMG 517 is seen from a 10% (w/v) Pluronic® F108 in OraPlus® suspension. Investigation of the suspension formulation revealed that AMG 517 forms a co‐crystal with sorbic acid, a preservative in OraPlus®. This co‐crystal of AMG 517 was isolated by coslurrying AMG 517 and sorbic acid; studied by DSC and XRD; and identified by solution NMR, TGA, and HPLC to be a 1:1 association of AMG 517 and sorbic acid. Single crystal structure analysis revealed a 1:1 co‐crystal of AMG 517 and sorbic acid, held together by two hydrogen bonds and other noncovalent, nonionic forces. The co‐crystal has better aqueous solubility initially as compared to AMG 517 free base but does revert back to a form of the free base hydrate during prolonged slurry in FaSIF (fasted simulated intestinal fluid). Pharmacokinetic evaluation of the co‐crystal in rats using 10% (w/v) Pluronic F108® in OraPlus® suspensions revealed that a 30 mg/kg dose in suspension had comparable exposure to a 500 mg/kg dose of the free base. © 2008 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:3942–3956, 2008</abstract><cop>Hoboken</cop><pub>Elsevier Inc</pub><pmid>18214948</pmid><doi>10.1002/jps.21280</doi><tpages>15</tpages></addata></record> |
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| subjects | Animals Benzothiazoles - blood Benzothiazoles - chemistry Benzothiazoles - pharmacokinetics bioavailability Biological and medical sciences Chromatography, High Pressure Liquid co-crystals Crystallization Crystallography, X-Ray General pharmacology Magnetic Resonance Spectroscopy Medical sciences Particle Size Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments physical characterization physical stability physicochemical properties Pyrimidines - blood Pyrimidines - chemistry Pyrimidines - pharmacokinetics Rats Rats, Sprague-Dawley Solubility TRPV Cation Channels - antagonists & inhibitors Water - chemistry |
| title | The Co‐Crystal Approach to Improve the Exposure of a Water‐Insoluble Compound: AMG 517 Sorbic Acid Co‐Crystal Characterization and Pharmacokinetics |
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