In vitro and in vivo characteristics of celecoxib in situ formed suspensions for intra-articular administration

TY - JOUR

T1 - In vitro and in vivo characteristics of celecoxib in situ formed suspensions for intra-articular administration

AU - Larsen, Susan Weng

AU - Frost, Anna Buus

AU - Østergaard, Jesper

AU - Thomsen, Maj Halling

AU - Jacobsen, Stine

AU - Skonberg, Christian

AU - Hansen, Steen Honore'

AU - Jensen, Henrik Michael Elvang

AU - Larsen, Claus Selch

PY - 2011/10

Y1 - 2011/10

N2 - 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.

AB - 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.

U2 - 10.1002/jps.22630

DO - 10.1002/jps.22630

M3 - Journal article

C2 - 21598256

SN - 0022-3549

VL - 100

SP - 4330

EP - 4337

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

IS - 10

ER -