Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2485878 | Journal of Pharmaceutical Sciences | 2007 | 17 Pages |
Abstract
Biopharmaceutical evaluation of crystalline celecoxib salts in novel solid formulations, which were designed to simultaneously facilitate dissolution and inhibit precipitation in vitro, showed fast and complete absorption in beagle dogs at doses up to 7.5Â mg/kg orally. In contrast, 5Â mg/kg celecoxib in the form of Celebrex® showed approximately 40% absolute bioavailability in a crossâover experiment. An in vitro-in vivo correlation was observed in dog, and a threshold level of in vitro dissolution needed to maximize in vivo performance was highlighted. Oral bioavailability was limited in the absence of excipient combinations that delayed precipitation of celecoxib free acid as the salt neutralized in the GI fluid. Formulations of crystal forms having high energy (a 'spring'), thus transiently increasing solubility in aqueous solution relative to the free acid, combined with excipients functioning as precipitation inhibitors ('parachutes') were shown to provide both enhanced dissolution and high oral bioavailability. © 2007 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2686-2702, 2007
Keywords
Related Topics
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Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Héctor R. Guzmán, Mark Tawa, Zhong Zhang, Pasut Ratanabanangkoon, Paul Shaw, Colin R. Gardner, Hongming Chen, JeanâPierre Moreau, Ãrn Almarsson, Julius F. Remenar,