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Celecoxib confinement within mesoporous silicon for enhanced oral bioavailability

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Wang F., Barnes T. J., Prestidge C. A.

Mesoporous Biomaterials

2014

vol. 1

issue 1

We investigate the physicochemical characteristics of celecoxib (CEL) entrapped within particles of an oxidized porous silicon matrix (pSiox); determine the oral dose response of CEL compared to pure drug and innovator formulation; develop in vivo-in vitro correlation (IVIVC). CEL was loaded into a pSiox matrix by solvent partitioning, with the physical state of the CEL characterized by FTIR, DSC, TGA and XRD, and correlated with in vitro dissolution behavior. Single dose pharmacokinetic parameters of orally dosed CEL were determined in fasted rats for aqueous suspensions of pure CEL, Celebrexr and CEL-pSiox microparticles. Physicochemical testing of CEL-pSiox formulation confirmed the entrapment of CEL within porous nanostructure in an amorphous or non-crystalline form. CEL-pSiox demonstrated superior pharmacokinetics compared with CEL particles or Celebrexr, i.e. increased absolute bioavailability (96.2% vs. 65.2% vs. 88.1%), increased Cmax (0.91 ± 0.09 μg/mL vs. 0.50 ± 0.16 μg/mL vs. 0.73 ± 0.23 μg/mL) and reduced Tmax (1.0 ± 0.0 h vs. 2.8 ± 0.8 h vs. 3.4 ± 1.0 h). Single point correlation was established between in vitro dissolution efficiency (% DE) and in vivo absolute bioavailability or Cmax . Porous silicon microparticles can be formulated as an effective orally dosed solid dispersion preparation for celecoxib

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1 Mesoporous Biomaterials

1 2014

1 Barnes T. J.

1 Prestidge C. A.

1 Wang F.

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Celecoxib confinement within mesoporous silicon for enhanced oral bioavailability