In vitro and in vivo characteristics of celecoxib in situ formed suspensions for intra-articular administration
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 so...
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| Published in | Journal of pharmaceutical sciences Vol. 100; no. 10; pp. 4330 - 4337 |
|---|---|
| Main Authors | , , , , , , , , |
| 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 | |
| Online Access | Get full text |
| ISSN | 0022-3549 1520-6017 1520-6017 |
| DOI | 10.1002/jps.22630 |
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| 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. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:4330–4337, 2011 |
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| AbstractList | 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 [PUBLICATION 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. 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.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. 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 |
| Author | Hansen, Steen Honoré Østergaard, Jesper Larsen, Susan Weng Jacobsen, Stine Frost, Anna Buus Thomsen, Maj Halling Jensen, Henrik Elvang Skonberg, Christian Larsen, Claus |
| Author_xml | – sequence: 1 givenname: Susan Weng surname: Larsen fullname: Larsen, Susan Weng organization: Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, DK-2100 Copenhagen Ø, Denmark – sequence: 2 givenname: Anna Buus surname: Frost fullname: Frost, Anna Buus organization: Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, DK-2100 Copenhagen Ø, Denmark – sequence: 3 givenname: Jesper surname: Østergaard fullname: Østergaard, Jesper organization: Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, DK-2100 Copenhagen Ø, Denmark – sequence: 4 givenname: Maj Halling surname: Thomsen fullname: Thomsen, Maj Halling organization: Department of Large Animal Sciences, Faculty of Life Sciences, University of Copenhagen, DK-2630 Taastrup, Denmark – sequence: 5 givenname: Stine surname: Jacobsen fullname: Jacobsen, Stine organization: Department of Large Animal Sciences, Faculty of Life Sciences, University of Copenhagen, DK-2630 Taastrup, Denmark – sequence: 6 givenname: Christian surname: Skonberg fullname: Skonberg, Christian organization: Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, DK-2100 Copenhagen Ø, Denmark – sequence: 7 givenname: Steen Honoré surname: Hansen fullname: Hansen, Steen Honoré organization: Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, DK-2100 Copenhagen Ø, Denmark – sequence: 8 givenname: Henrik Elvang surname: Jensen fullname: Jensen, Henrik Elvang organization: Department of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen, DK-1870 Frederiksberg C, Denmark – sequence: 9 givenname: Claus surname: Larsen fullname: Larsen, Claus email: csl@farma.ku.dk organization: Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, DK-2100 Copenhagen Ø, Denmark |
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| CitedBy_id | crossref_primary_10_1016_j_xphs_2020_01_003 crossref_primary_10_1016_j_jconrel_2018_05_029 crossref_primary_10_3109_03639045_2014_884129 crossref_primary_10_1115_1_4044892 crossref_primary_10_1016_j_biomaterials_2015_02_109 crossref_primary_10_1016_S1773_2247_13_50048_7 crossref_primary_10_1016_j_biomaterials_2014_05_064 crossref_primary_10_1016_j_ijpharm_2019_04_083 crossref_primary_10_1016_j_biomaterials_2013_07_046 crossref_primary_10_1111_evj_13561 crossref_primary_10_1016_j_ejpb_2018_05_001 crossref_primary_10_1016_j_ejpb_2018_07_026 crossref_primary_10_1021_acs_molpharmaceut_4c00665 crossref_primary_10_1016_j_cveq_2016_04_003 |
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| Keywords | 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 |
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| SubjectTerms | 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 |
| Title | In vitro and in vivo characteristics of celecoxib in situ formed suspensions for intra-articular administration |
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