Influence of polymers on the bioavailability of microencapsulated celecoxib.
Celecoxib, a selective COX-2 inhibitor, primarily used in treatment of osteoarthritis, rheumatoid arthritis and acute pain was encapsulated in microparticles composed of various polyesters, polymethacrylates or cellulose derivatives used alone or blended. The influence of polymers on microparticle mean diameter, encapsulation efficiency and in vitro and in vivo celecoxib release was investigated. Microparticles were in the size range 11-37 microm. Encapsulation efficiency was optimal due to poor aqueous solubility of celecoxib. Considering in vitro release, microparticles could be divided into drug delivery systems with fast and slow release profiles. Microparticles prepared with poly-epsilon-caprolactone, Eudragit RS and low viscosity ethylcellulose, together with physical mixture of celecoxib with lactose and Celebrex, were tested in vivo. Relative bioavailability of celecoxib was below 20% in all cases and was probably the consequence of a slow in vivo release of celecoxib from microparticles or low wettability in the case of Celebrex and physical mixture.
Homar
Miha
M
Lek Pharmaceuticals d.d., Sandoz Development Center Slovenia, Ljubljana, Slovenia.
Ubrich
Nathalie
N
El Ghazouani
Fatima
F
Kristl
Julijana
J
Kerc
Janez
J
Maincent
Philippe
P
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D000068579:Celecoxib; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004339:Drug Compounding; D016503:Drug Delivery Systems; D007785:Lactose / Q000737:chemistry; D008297:Male; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D011720:Pyrazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D011817:Rabbits; D013449:Sulfonamides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*
D016861:Cyclooxygenase Inhibitors; D011108:Polymers; D011720:Pyrazoles; D013449:Sulfonamides; C013517:ethyl cellulose; D002482:Cellulose; D007785:Lactose; D000068579:Celecoxib