Preparation of celecoxib-dimethyl-β-cyclodextrin inclusion complex: characterization and in vitro permeation study

The ability of 2,6-di-O-methyl-β-cyclodextrin (DM-β-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-β-Cyd complexes and 1H-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-β-Cyd. DM-β-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.