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dc.contributor.authorTan, Angel
dc.contributor.authorDavey, Andrew K
dc.contributor.authorPrestidge, Clive A
dc.date.accessioned2017-05-03T16:01:06Z
dc.date.available2017-05-03T16:01:06Z
dc.date.issued2011
dc.date.modified2011-11-08T07:59:37Z
dc.identifier.issn0724-8741
dc.identifier.doi10.1007/s11095-011-0458-x
dc.identifier.urihttp://hdl.handle.net/10072/41414
dc.description.abstractPurpose To investigate the dose linearity of celecoxib (CEL) pharmacokinetics from various non-lipid and lipid-based formulations; to probe the mechanisms of CEL absorption from a nano-structured silica-lipid hybrid (SLH) microparticle dosage form. Methods Single-dose pharmacokinetic parameters of CEL were determined in fasted rats at dose levels of 5, 20 and 50 mg/kg in aqueous suspensions of pure CEL, Celebrexnd CEL-SLH microparticles formulated using medium-chain lipids (Miglyol 812 or Capmul MCM) and Aerosililica nanoparticles. An in vitro lipolysis model was used to characterise the dynamic solubilisation state of CEL under digesting conditions. Results CEL-SLH formulations and Celebrexonsistently produced a 2-fold higher maximum plasma concentration (Cmax) and bioavailability (AUC0?8) than pure CEL in a doselinear manner within the dose range of 5-50 mg/kg CEL (R2> 0.8). Lipolysis drug phase partition data indicate a 2.5-7.5-fold higher CEL solubilising capacity resulting from the digestion of SLH microparticles as compared to the simulated fasted state endogenous micelles. Strong correlations were obtained between maximum CEL solubilisation levels during lipolysis and in vivo pharmacokinetic parameters (R2>0.9). Conclusions Collectively, the results highlight the potential of the SLH microparticles in enhancing the bioavailability of CEL in a dose-linear manner as facilitated by supersaturated solubilisation of CEL in the intestinal milieu.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherSpringer New York LLC
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom2273
dc.relation.ispartofpageto2287
dc.relation.ispartofissue9
dc.relation.ispartofjournalPharmaceutical Research
dc.relation.ispartofvolume28
dc.rights.retentionY
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchPharmaceutical sciences
dc.subject.fieldofresearchcode3214
dc.subject.fieldofresearchcode321405
dc.titleSilica-Lipid Hybrid (SLH) Versus Non-lipid Formulations for Optimising the Dose-Dependent Oral Absorption of Celecoxib
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2011
gro.hasfulltextNo Full Text
gro.griffith.authorDavey, Andrew


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