title: In vitro and in vivo characteristics of celecoxib in situ formed suspensions for intra-articular administration.
abstract: The objective of the present study was to explore the potential of using an in situ suspension forming drug delivery system of celecoxib to provide sustained drug exposure in the joint cavity following intra-articular administration. In vitro, precipitates were formed upon addition of a 400 mg/mL solution of celecoxib in polyethylene glycol 400 (PEG 400) to phosphate buffer, pH 7.4, or synovial fluid. The in vitro release profiles of the in situ formed suspensions were characterized by an initial fast release followed by a slower constant flux. In buffer solutions, these fluxes were comparable to those determined for a preformed suspension containing celecoxib in its most stable crystal form despite the in situ formed precipitates contained a mixture of two crystal forms of celecoxib as determined by X-ray powder diffraction. In situ suspension formation in synovial fluid was subject to considerable variation. A relatively high dose of celecoxib, corresponding to 1.25 mg/kg, in the form of PEG 400 solution (400 mg/mL) was injected into the radiocarpal joint in four horses. Celecoxib was present in serum samples taken over 10 days and in the joint tissue (post mortem), strongly indicating that joint sustained celecoxib exposure can be achieved using in situ suspension formation.
authors: Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, DK-2100 Copenhagen Ø, Denmark.
authors: Susan Weng
authors: SW
authors: Larsen
authors: Anna Buus
authors: AB
authors: Frost
authors: Jesper
authors: J
authors: Ostergaard
authors: Maj Halling
authors: MH
authors: Thomsen
authors: Stine
authors: S
authors: Jacobsen
authors: Christian
authors: C
authors: Skonberg
authors: Steen Honoré
authors: SH
authors: Hansen
authors: Henrik Elvang
authors: HE
authors: Jensen
authors: Claus
authors: C
authors: Larsen