Preparation of celecoxib-dimethyl-beta-cyclodextrin inclusion complex: characterization and in vitro permeation study.
The ability of 2,6-di-O-methyl-beta-cyclodextrin (DM-beta-Cyd) to include the anti-inflammatory drug celecoxib (CCB) was evaluated. The complex was prepared by kneading and freeze-drying methods and was characterized in the solid state and in aqueous solution. Water solubility and dissolution rate of CCB, in a medium simulating gastric fluid, significantly increased after complexation, with complete dissolution obtained after 30 and 180 min for the freeze-dried and kneaded complexes respectively. Phase solubility studies showed Ap-type diagrams. Stability constants for the 1:1 and 1:2 CCB-DM-beta-Cyd complexes and (1)H-NMR studies suggested a probable 1:1 inclusion complex and only an external interaction for the second Cyd molecule. Thermodynamic parameters of the binding process showed the existence of van der Waals forces between CCB and DM-beta-Cyd. DM-beta-Cyd influenced the permeation of CCB through the CaCo-2 cells monolayer. The increase of permeation observed was due to the fast dissolution rate of the included drug and to a destabilizing action exerted by the macrocycle on the biomembrane.
Ventura
Cinzia Anna
CA
Pharmaco-Chemical Department, Faculty of Pharmacy, University of Messina, Viale Annunziata, I-98168 Messina, Italy. cventura@pharma.unime.it
Giannone
Ignazio
I
Paolino
Donatella
D
Pistarà
Venerando
V
Corsaro
Antonino
A
Puglisi
Giovanni
G
D018938:Caco-2 Cells; D000068579:Celecoxib; D002463:Cell Membrane Permeability; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011720:Pyrazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility; D013449:Sulfonamides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D013816:Thermodynamics; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000493:pharmacokinetics*
D004337:Drug Carriers; D011720:Pyrazoles; D013449:Sulfonamides; D047392:beta-Cyclodextrins; C038119:heptakis(2,6-O-dimethyl)beta-cyclodextrin; D000068579:Celecoxib