title: In situ intestinal permeability and in vivo oral bioavailability of celecoxib in supersaturating self-emulsifying drug delivery system.
abstract: In order to characterize the in situ intestinal permeability and in vivo oral bioavailability of celecoxib (CXB), a poorly water-soluble cyclooxygenase (COX)-2 inhibitor, various formulations including the self-emulsifying drug delivery system (SEDDS) and supersaturating SEDDS (S-SEDDS) were compared. The S-SEDDS formulation was obtained by adding Soluplus as a precipitation inhibitor to SEDDS, composed of Capryol 90 as oil, Tween 20 as surfactant, and Tetraglycol as cosurfactant (1:4.5:4.5 in volume ratio). An in situ single pass intestinal perfusion study in rats was performed with CXB-dissolved solutions at a concentration of 40 μg/mL. The effective permeability (Peff) of CXB in the control solution (2.5 v/v% Tween 20-containing PBS) was 6.39 × 10(-5) cm/s. The Peff value was significantly increased (P < 0.05) by the lipid-based formulation, yielding 1.5- and 2.9-fold increases for the SEDDS and S-SEDDS solutions, respectively, compared to the control solution. After oral administration of various formulations to rats at the equivalent dose of 100 mg/kg of CXB, the plasma drug level was measured by LC-MS/MS. The relative bioavailabilities of SEDDS and S-SEDDS were 263 and 355 %, respectively, compared to the CXB suspension as a reference. In particular, S-SEDDS revealed the highest Cmax and the smallest Tmax, indicating rapid and enhanced absorption with this formulation. This study illustrates the potential use of the S-SEDDS formulation in the oral delivery of poorly water-soluble compounds.
authors.affiliation: Drug Delivery Research Laboratory, College of Pharmacy, Chung-Ang University, 221 Heuksuk-dong, Dongjak-gu, Seoul, 156-756, Korea.
authors.forename: Woo Heon
authors.initials: WH
authors.lastname: Song
authors.forename: Dong Woo
authors.initials: DW
authors.lastname: Yeom
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Lee
authors.forename: Kyung Min
authors.initials: KM
authors.lastname: Lee
authors.forename: Hyun Joon
authors.initials: HJ
authors.lastname: Yoo
authors.forename: Bo Ram
authors.initials: BR
authors.lastname: Chae
authors.forename: Seh Hyon
authors.initials: SH
authors.lastname: Song
authors.forename: Young Wook
authors.initials: YW
authors.lastname: Choi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D000068579:Celecoxib; D002626:Chemistry, Pharmaceutical; D002853:Chromatography, Liquid; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers; D004655:Emulsions; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008823:Micelles; D010539:Permeability; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry; D011409:Propylene Glycols / Q000737:chemistry; D011720:Pyrazoles / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D013501:Surface-Active Agents / Q000737:chemistry; D053719:Tandem Mass Spectrometry; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D004337:Drug Carriers; D004655:Emulsions; D008823:Micelles; D011108:Polymers; D011136:Polysorbates; D011145:Polyvinyls; D011409:Propylene Glycols; D011720:Pyrazoles; D013449:Sulfonamides; D013501:Surface-Active Agents; C584816:capryol propylene glycol monocaprylate; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D011092:Polyethylene Glycols; D000068579:Celecoxib; C018557:glycofurol