caa a22 4500 445312041 CHVBK 20180317142633.0 cr unu---uuuuu 170323e20110901xx s 000 0 eng 10.1007/s11095-011-0458-x doi (NATIONALLICENCE)springer-10.1007/s11095-011-0458-x Silica-Lipid Hybrid (SLH) Versus Non-lipid Formulations for Optimising the Dose-Dependent Oral Absorption of Celecoxib [Elektronische Daten] [Angel Tan, Andrew Davey, Clive Prestidge] ABSTRACT: Purpose: 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 50mg/kg in aqueous suspensions of pure CEL, Celebrex® and CEL-SLH microparticles formulated using medium-chain lipids (Miglyol 812 or Capmul MCM) and Aerosil® silica 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® consistently produced a 2-fold higher maximum plasma concentration (C max) and bioavailability (AUC 0→∞) than pure CEL in a dose-linear manner within the dose range of 5-50mg/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. Springer Science+Business Media, LLC, 2011 celecoxib nationallicence dose-dependent absorption nationallicence in vitro - in vivo correlations nationallicence lipid-based formulation nationallicence lipolysis nationallicence Tan Angel Ian Wark Research Institute, ARC Special Research Centre for Particle and Material, Interfaces, University of South Australia, 5095, Mawson Lakes, SA, Australia aut Davey Andrew Sansom Institute, School of Pharmacy and Medical Science, University of South Australia, 5000, Adelaide, SA, Australia aut Prestidge Clive Ian Wark Research Institute, ARC Special Research Centre for Particle and Material, Interfaces, University of South Australia, 5095, Mawson Lakes, SA, Australia aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/9(2011-09-01), 2273-2287 0724-8741 28:9<2273 2011 28 11095 https://doi.org/10.1007/s11095-011-0458-x text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0458-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Tan Angel Ian Wark Research Institute, ARC Special Research Centre for Particle and Material, Interfaces, University of South Australia, 5095, Mawson Lakes, SA, Australia aut NATIONALLICENCE 700 1- Davey Andrew Sansom Institute, School of Pharmacy and Medical Science, University of South Australia, 5000, Adelaide, SA, Australia aut NATIONALLICENCE 700 1- Prestidge Clive Ian Wark Research Institute, ARC Special Research Centre for Particle and Material, Interfaces, University of South Australia, 5095, Mawson Lakes, SA, Australia aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/9(2011-09-01), 2273-2287 0724-8741 28:9<2273 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer