Improved bioavailability of darunavir by use of κ-carrageenan versus microcrystalline cellulose as pelletisation aid
The aim of this study was to produce pellet formulations containing a high drug load (80%) of the poorly soluble HIV-protease inhibitor darunavir, using wet extrusion/spheronisation with κ-carrageenan or microcrystalline cellulose (MCC) as pelletisation aid. Drug release was assessed in vitro by a s...
Gespeichert in:
| Veröffentlicht in: | European journal of pharmaceutics and biopharmaceutics 2009-08, Vol.72 (3), p.614-620 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 620 |
|---|---|
| container_issue | 3 |
| container_start_page | 614 |
| container_title | European journal of pharmaceutics and biopharmaceutics |
| container_volume | 72 |
| creator | Thommes, Markus Baert, Lieven van ’t Klooster, Gerben Geldof, Marian Schueller, Laurent Rosier, Jan Kleinebudde, Peter |
| description | The aim of this study was to produce pellet formulations containing a high drug load (80%) of the poorly soluble HIV-protease inhibitor darunavir, using wet extrusion/spheronisation with κ-carrageenan or microcrystalline cellulose (MCC) as pelletisation aid. Drug release was assessed
in vitro by a standardized paddle-dissolution test and
in vivo by a single-dose pharmacokinetic study in dogs. Mean dissolution time (MDT) was 78.2
±
3.5
h from MCC pellets (1301
±
301
μm) and 6.1
±
0.7
min from κ-carrageenan pellets (966
±
136
μm). In contrast to κ-carrageenan pellets, MCC pellets did not disintegrate and showed a diffusion-controlled drug release. In line with the
in vitro findings, the darunavir peak plasma levels and exposure after the administration of a 300
mg dose were more than 60-fold higher when formulated with κ-carrageenan pellets when compared with MCC pellets, and 10-fold higher after co-administration with 10
mg/kg of ritonavir. The relative bioavailability of darunavir versus the reference tablet (
F
rel) was 155% with κ-carrageenan pellets and 2% with MCC pellets without ritonavir, while 78% and 9%, respectively, in presence of ritonavir. In conclusion, when compared with MCC pellets, the bioavailability of darunavir was substantially improved in κ-carrageenan pellets, likely due to their better disintegration behavior. |
| doi_str_mv | 10.1016/j.ejpb.2009.03.004 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_733360586</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S093964110900099X</els_id><sourcerecordid>733360586</sourcerecordid><originalsourceid>FETCH-LOGICAL-c385t-8ddf915da021dc0e5df9aa0d69dec18586df0723ceb48236500f2af8d27f48c33</originalsourceid><addsrcrecordid>eNp9kMuq1TAUhoMonu3RF3AgmYij1pWklxScyMHLgQNOdBxWk1XJJm23SVvYr-ZDnGcyZW905iis8P0_a32MvRZQChDN-2NJx1NfSoCuBFUCVE_YQehWFaqqxFN2gE51RVMJccNepHSETLS1fs5uRKdAdbI7sPV-PMV5I8d7P-OGPmDvg1_OfB64w7hOuPnI-zNfE-1_j78LizHiT6IJJ75RTGvio7dxtvGcFgzBT8QthbCGOWcw8VMeaPEJFz9PHL17yZ4NGBK9ur637MfnT9_vvhYP377c3318KKzS9VJo54ZO1A5BCmeB6jwigms6R1boWjdugFYqS32lpWpqgEHioJ1sh0pbpW7Zu0tvvvHXSmkxo0_7ajjRvCbTKqUayD2ZlBcy35FSpMGcoh8xno0As9s2R7PbNrttA8pklzn05lq_9iO5f5Gr3gy8vQKYLIYh4mR9-stJ0UqtlM7chwtHWcbmKZpkPU2WnI9kF-Nm_789_gDujqF2</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>733360586</pqid></control><display><type>article</type><title>Improved bioavailability of darunavir by use of κ-carrageenan versus microcrystalline cellulose as pelletisation aid</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><creator>Thommes, Markus ; Baert, Lieven ; van ’t Klooster, Gerben ; Geldof, Marian ; Schueller, Laurent ; Rosier, Jan ; Kleinebudde, Peter</creator><creatorcontrib>Thommes, Markus ; Baert, Lieven ; van ’t Klooster, Gerben ; Geldof, Marian ; Schueller, Laurent ; Rosier, Jan ; Kleinebudde, Peter</creatorcontrib><description>The aim of this study was to produce pellet formulations containing a high drug load (80%) of the poorly soluble HIV-protease inhibitor darunavir, using wet extrusion/spheronisation with κ-carrageenan or microcrystalline cellulose (MCC) as pelletisation aid. Drug release was assessed
in vitro by a standardized paddle-dissolution test and
in vivo by a single-dose pharmacokinetic study in dogs. Mean dissolution time (MDT) was 78.2
±
3.5
h from MCC pellets (1301
±
301
μm) and 6.1
±
0.7
min from κ-carrageenan pellets (966
±
136
μm). In contrast to κ-carrageenan pellets, MCC pellets did not disintegrate and showed a diffusion-controlled drug release. In line with the
in vitro findings, the darunavir peak plasma levels and exposure after the administration of a 300
mg dose were more than 60-fold higher when formulated with κ-carrageenan pellets when compared with MCC pellets, and 10-fold higher after co-administration with 10
mg/kg of ritonavir. The relative bioavailability of darunavir versus the reference tablet (
F
rel) was 155% with κ-carrageenan pellets and 2% with MCC pellets without ritonavir, while 78% and 9%, respectively, in presence of ritonavir. In conclusion, when compared with MCC pellets, the bioavailability of darunavir was substantially improved in κ-carrageenan pellets, likely due to their better disintegration behavior.</description><identifier>ISSN: 0939-6411</identifier><identifier>EISSN: 1873-3441</identifier><identifier>DOI: 10.1016/j.ejpb.2009.03.004</identifier><identifier>PMID: 19303929</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Animals ; Bioavailability ; Biological and medical sciences ; Biological Availability ; Carrageenan ; Carrageenan - blood ; Carrageenan - pharmacokinetics ; Cellulose - blood ; Cellulose - pharmacokinetics ; Cross-Over Studies ; Darunavir ; Dogs ; Drug Implants - pharmacokinetics ; Extrusion ; General pharmacology ; Male ; Medical sciences ; Microcrystalline cellulose ; Pellets ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Spheronisation ; Sulfonamides - blood ; Sulfonamides - pharmacokinetics ; TMC114</subject><ispartof>European journal of pharmaceutics and biopharmaceutics, 2009-08, Vol.72 (3), p.614-620</ispartof><rights>2009 Elsevier B.V.</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c385t-8ddf915da021dc0e5df9aa0d69dec18586df0723ceb48236500f2af8d27f48c33</citedby><cites>FETCH-LOGICAL-c385t-8ddf915da021dc0e5df9aa0d69dec18586df0723ceb48236500f2af8d27f48c33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejpb.2009.03.004$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21728338$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19303929$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Thommes, Markus</creatorcontrib><creatorcontrib>Baert, Lieven</creatorcontrib><creatorcontrib>van ’t Klooster, Gerben</creatorcontrib><creatorcontrib>Geldof, Marian</creatorcontrib><creatorcontrib>Schueller, Laurent</creatorcontrib><creatorcontrib>Rosier, Jan</creatorcontrib><creatorcontrib>Kleinebudde, Peter</creatorcontrib><title>Improved bioavailability of darunavir by use of κ-carrageenan versus microcrystalline cellulose as pelletisation aid</title><title>European journal of pharmaceutics and biopharmaceutics</title><addtitle>Eur J Pharm Biopharm</addtitle><description>The aim of this study was to produce pellet formulations containing a high drug load (80%) of the poorly soluble HIV-protease inhibitor darunavir, using wet extrusion/spheronisation with κ-carrageenan or microcrystalline cellulose (MCC) as pelletisation aid. Drug release was assessed
in vitro by a standardized paddle-dissolution test and
in vivo by a single-dose pharmacokinetic study in dogs. Mean dissolution time (MDT) was 78.2
±
3.5
h from MCC pellets (1301
±
301
μm) and 6.1
±
0.7
min from κ-carrageenan pellets (966
±
136
μm). In contrast to κ-carrageenan pellets, MCC pellets did not disintegrate and showed a diffusion-controlled drug release. In line with the
in vitro findings, the darunavir peak plasma levels and exposure after the administration of a 300
mg dose were more than 60-fold higher when formulated with κ-carrageenan pellets when compared with MCC pellets, and 10-fold higher after co-administration with 10
mg/kg of ritonavir. The relative bioavailability of darunavir versus the reference tablet (
F
rel) was 155% with κ-carrageenan pellets and 2% with MCC pellets without ritonavir, while 78% and 9%, respectively, in presence of ritonavir. In conclusion, when compared with MCC pellets, the bioavailability of darunavir was substantially improved in κ-carrageenan pellets, likely due to their better disintegration behavior.</description><subject>Animals</subject><subject>Bioavailability</subject><subject>Biological and medical sciences</subject><subject>Biological Availability</subject><subject>Carrageenan</subject><subject>Carrageenan - blood</subject><subject>Carrageenan - pharmacokinetics</subject><subject>Cellulose - blood</subject><subject>Cellulose - pharmacokinetics</subject><subject>Cross-Over Studies</subject><subject>Darunavir</subject><subject>Dogs</subject><subject>Drug Implants - pharmacokinetics</subject><subject>Extrusion</subject><subject>General pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microcrystalline cellulose</subject><subject>Pellets</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Spheronisation</subject><subject>Sulfonamides - blood</subject><subject>Sulfonamides - pharmacokinetics</subject><subject>TMC114</subject><issn>0939-6411</issn><issn>1873-3441</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMuq1TAUhoMonu3RF3AgmYij1pWklxScyMHLgQNOdBxWk1XJJm23SVvYr-ZDnGcyZW905iis8P0_a32MvRZQChDN-2NJx1NfSoCuBFUCVE_YQehWFaqqxFN2gE51RVMJccNepHSETLS1fs5uRKdAdbI7sPV-PMV5I8d7P-OGPmDvg1_OfB64w7hOuPnI-zNfE-1_j78LizHiT6IJJ75RTGvio7dxtvGcFgzBT8QthbCGOWcw8VMeaPEJFz9PHL17yZ4NGBK9ur637MfnT9_vvhYP377c3318KKzS9VJo54ZO1A5BCmeB6jwigms6R1boWjdugFYqS32lpWpqgEHioJ1sh0pbpW7Zu0tvvvHXSmkxo0_7ajjRvCbTKqUayD2ZlBcy35FSpMGcoh8xno0As9s2R7PbNrttA8pklzn05lq_9iO5f5Gr3gy8vQKYLIYh4mR9-stJ0UqtlM7chwtHWcbmKZpkPU2WnI9kF-Nm_789_gDujqF2</recordid><startdate>20090801</startdate><enddate>20090801</enddate><creator>Thommes, Markus</creator><creator>Baert, Lieven</creator><creator>van ’t Klooster, Gerben</creator><creator>Geldof, Marian</creator><creator>Schueller, Laurent</creator><creator>Rosier, Jan</creator><creator>Kleinebudde, Peter</creator><general>Elsevier B.V</general><general>Elsevier</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>7X8</scope></search><sort><creationdate>20090801</creationdate><title>Improved bioavailability of darunavir by use of κ-carrageenan versus microcrystalline cellulose as pelletisation aid</title><author>Thommes, Markus ; Baert, Lieven ; van ’t Klooster, Gerben ; Geldof, Marian ; Schueller, Laurent ; Rosier, Jan ; Kleinebudde, Peter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c385t-8ddf915da021dc0e5df9aa0d69dec18586df0723ceb48236500f2af8d27f48c33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Bioavailability</topic><topic>Biological and medical sciences</topic><topic>Biological Availability</topic><topic>Carrageenan</topic><topic>Carrageenan - blood</topic><topic>Carrageenan - pharmacokinetics</topic><topic>Cellulose - blood</topic><topic>Cellulose - pharmacokinetics</topic><topic>Cross-Over Studies</topic><topic>Darunavir</topic><topic>Dogs</topic><topic>Drug Implants - pharmacokinetics</topic><topic>Extrusion</topic><topic>General pharmacology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microcrystalline cellulose</topic><topic>Pellets</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Spheronisation</topic><topic>Sulfonamides - blood</topic><topic>Sulfonamides - pharmacokinetics</topic><topic>TMC114</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Thommes, Markus</creatorcontrib><creatorcontrib>Baert, Lieven</creatorcontrib><creatorcontrib>van ’t Klooster, Gerben</creatorcontrib><creatorcontrib>Geldof, Marian</creatorcontrib><creatorcontrib>Schueller, Laurent</creatorcontrib><creatorcontrib>Rosier, Jan</creatorcontrib><creatorcontrib>Kleinebudde, Peter</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>MEDLINE - Academic</collection><jtitle>European journal of pharmaceutics and biopharmaceutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Thommes, Markus</au><au>Baert, Lieven</au><au>van ’t Klooster, Gerben</au><au>Geldof, Marian</au><au>Schueller, Laurent</au><au>Rosier, Jan</au><au>Kleinebudde, Peter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Improved bioavailability of darunavir by use of κ-carrageenan versus microcrystalline cellulose as pelletisation aid</atitle><jtitle>European journal of pharmaceutics and biopharmaceutics</jtitle><addtitle>Eur J Pharm Biopharm</addtitle><date>2009-08-01</date><risdate>2009</risdate><volume>72</volume><issue>3</issue><spage>614</spage><epage>620</epage><pages>614-620</pages><issn>0939-6411</issn><eissn>1873-3441</eissn><abstract>The aim of this study was to produce pellet formulations containing a high drug load (80%) of the poorly soluble HIV-protease inhibitor darunavir, using wet extrusion/spheronisation with κ-carrageenan or microcrystalline cellulose (MCC) as pelletisation aid. Drug release was assessed
in vitro by a standardized paddle-dissolution test and
in vivo by a single-dose pharmacokinetic study in dogs. Mean dissolution time (MDT) was 78.2
±
3.5
h from MCC pellets (1301
±
301
μm) and 6.1
±
0.7
min from κ-carrageenan pellets (966
±
136
μm). In contrast to κ-carrageenan pellets, MCC pellets did not disintegrate and showed a diffusion-controlled drug release. In line with the
in vitro findings, the darunavir peak plasma levels and exposure after the administration of a 300
mg dose were more than 60-fold higher when formulated with κ-carrageenan pellets when compared with MCC pellets, and 10-fold higher after co-administration with 10
mg/kg of ritonavir. The relative bioavailability of darunavir versus the reference tablet (
F
rel) was 155% with κ-carrageenan pellets and 2% with MCC pellets without ritonavir, while 78% and 9%, respectively, in presence of ritonavir. In conclusion, when compared with MCC pellets, the bioavailability of darunavir was substantially improved in κ-carrageenan pellets, likely due to their better disintegration behavior.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>19303929</pmid><doi>10.1016/j.ejpb.2009.03.004</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0939-6411 |
| ispartof | European journal of pharmaceutics and biopharmaceutics, 2009-08, Vol.72 (3), p.614-620 |
| issn | 0939-6411 1873-3441 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_733360586 |
| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Animals Bioavailability Biological and medical sciences Biological Availability Carrageenan Carrageenan - blood Carrageenan - pharmacokinetics Cellulose - blood Cellulose - pharmacokinetics Cross-Over Studies Darunavir Dogs Drug Implants - pharmacokinetics Extrusion General pharmacology Male Medical sciences Microcrystalline cellulose Pellets Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Spheronisation Sulfonamides - blood Sulfonamides - pharmacokinetics TMC114 |
| title | Improved bioavailability of darunavir by use of κ-carrageenan versus microcrystalline cellulose as pelletisation aid |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T03%3A58%3A21IST&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=Improved%20bioavailability%20of%20darunavir%20by%20use%20of%20%CE%BA-carrageenan%20versus%20microcrystalline%20cellulose%20as%20pelletisation%20aid&rft.jtitle=European%20journal%20of%20pharmaceutics%20and%20biopharmaceutics&rft.au=Thommes,%20Markus&rft.date=2009-08-01&rft.volume=72&rft.issue=3&rft.spage=614&rft.epage=620&rft.pages=614-620&rft.issn=0939-6411&rft.eissn=1873-3441&rft_id=info:doi/10.1016/j.ejpb.2009.03.004&rft_dat=%3Cproquest_cross%3E733360586%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=733360586&rft_id=info:pmid/19303929&rft_els_id=S093964110900099X&rfr_iscdi=true |