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

• Published in: Journal of pharmaceutical sciences Vol. 100; no. 10; pp. 4330 - 4337
• Main Authors: Larsen, Susan Weng, Frost, Anna Buus, Østergaard, Jesper, Thomsen, Maj Halling, Jacobsen, Stine, Skonberg, Christian, Hansen, Steen Honoré, Jensen, Henrik Elvang, Larsen, Claus
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.10.2011; Wiley Subscription Services, Inc., A Wiley Company; Wiley; American Pharmaceutical Association; Elsevier Limited
• Subjects: Animals; Biological and medical sciences; Buffers; Celecoxib; Chemistry, Pharmaceutical; controlled release; Crystallization; Crystallography, X-Ray; Cyclooxygenase 2 Inhibitors - administration & dosage; Cyclooxygenase 2 Inhibitors - blood; Cyclooxygenase 2 Inhibitors - chemistry; Cyclooxygenase 2 Inhibitors - pharmacokinetics; Delayed-Action Preparations; Drug Stability; formulation vehicle; General pharmacology; Horses; Hydrogen-Ion Concentration; in vitro models; injectables; Injections, Intra-Articular; Joints - metabolism; Medical sciences; Pharmaceutical Solutions; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyethylene Glycols - chemistry; Powder Diffraction; precipitation; Pyrazoles - administration & dosage; Pyrazoles - blood; Pyrazoles - chemistry; Pyrazoles - pharmacokinetics; solid state; Solubility; Sulfonamides - administration & dosage; Sulfonamides - blood; Sulfonamides - chemistry; Sulfonamides - pharmacokinetics; suspensions; Technology, Pharmaceutical - methods; Tissue Distribution; injectables; formulation vehicle; precipitation; controlled release; in vitro models; suspensions; solid state; Prostaglandin-endoperoxide synthase; Pharmaceutical technology; Enzyme; Controlled release form; Control release polymer; In situ; Enzyme inhibitor; Suspension; Cyclooxygenase 2 inhibitor; Celecoxib; In vitro; Non steroidal antiinflammatory agent; Solid state; In vivo; Precipitation; Intraarticular administration; Formulation; Dosage form; Oxidoreductases
• ISSN: 0022-3549; 1520-6017; 1520-6017
• DOI: 10.1002/jps.22630

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. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:4330–4337, 2011