| Co-administration of darunavir and a new pharmacokinetic booster: formulation strategies and evaluation in dogs. | |
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MedLine Citation:
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PMID: 20685614 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Various formulations for combination of the anti-HIV protease inhibitor darunavir (DRV) and TMC41629, a pharmacokinetic booster for DRV, were studied. TMC41629 (a BCS-IV compound) was formulated in capsules, as polyethylene glycol 400 (PEG400) solution, binary or ternary self-microemulsifying drug delivery system (SMEDDS), inclusion complex with hydroxypropyl-beta-cyclodextrin (HPbetaCD) or polyvinylpyrrolidone-co-vinylacetate 64 (PVP/VA64) extrudate. In addition, tablets were prepared using unmilled or micronized powder and a disintegrant. On co-administration with DRV tablets in dogs, DRV plasma concentration levels were boosted by TMC41629, the PVP/VA64 extrudate achieving the highest DRV levels (2-fold increase). Yet, with extrudate prepared with both compounds, no boosting effect was observed, likely due to transition of DRV from crystalline solvate to amorphous state. Therefore, a co-formulation, combining DRV as crystalline solvate with amorphous TMC41629, was developed. DRV/kappa-carrageenan 80/20% (w/w) beads coated with TMC41629 released at least 80% within 1h in 0.01M HCl with 0.5% sodium lauryl sulphate, TMC41629 dissolving faster than DRV. In dogs, the DRV exposure increased 2.7-fold with the TMC41629-coated beads relative to DRV alone, yet remained lower, but less variable, than following co-administration as separate formulations. Coating of TMC41629 on DRV/kappa-carrageenan beads is a suitable technique for co-formulation, whereby TMC41629 can function as a booster of DRV. |
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Authors:
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Elke Van Gyseghem; Lieven Baert; Pieter Van Remoortere; Gerben van 't Klooster; Marie-Claude Rouan; Jody Voorspoels; Herman de Kock; Laurent Schueller; Jan Rosier; Liesbeth Grooten; Guy Van den Mooter |
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Publication Detail:
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Type: Journal Article Date: 2010-06-08 |
Journal Detail:
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Title: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences Volume: 41 ISSN: 1879-0720 ISO Abbreviation: Eur J Pharm Sci Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-08-23 Completed Date: 2010-12-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9317982 Medline TA: Eur J Pharm Sci Country: Netherlands |
Other Details:
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Languages: eng Pagination: 193-200 Citation Subset: IM |
Affiliation:
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Laboratorium voor Farmacotechnologie en Biofarmacie, Katholieke Universiteit Leuven, Leuven, Belgium. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Chemistry, Pharmaceutical Dogs HIV Protease Inhibitors / administration & dosage*, pharmacokinetics Sulfonamides / administration & dosage*, pharmacokinetics Tablets |
| Chemical | |
Reg. No./Substance:
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0/HIV Protease Inhibitors; 0/Sulfonamides; 0/Tablets; 0/darunavir |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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