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

Preparation of celecoxib-dimethyl-?-cyclodextrin inclusion complex: characterization and in vitro permeation study
Received 6 December 2004; revised 1 March 2005; accepted 1 March 2005. Available online 2 April 2005.
Cinzia Anna Venturaa, , , Ignazio Giannoneb, Donatella Paolinoc, Venerando Pistar?d, Antonino Corsarod and Giovanni Puglisib
European Journal of Medicinal Chemistry
ScienceDirect
aPharmaco-Chemical Department, Faculty of Pharmacy, University of Messina, V. le Annunziata, I-98168 Messina, Italy
bDepartment of Pharmaceutical Sciences, University of Catania, V. le A. Doria, 6-I-95125 Catania, Italy
cPharmacobiological Department, University of Catanzaro ?Magna Gr?cia?, I-88021 Catanzaro, Italy
dDepartment of Chemical Sciences, University of Catania, V. le A. Doria, 6-I-95125 Catania, Italy
Abstract
The ability of 2,6-di-O-methyl-?-cyclodextrin (DM-?-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-?-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-?-Cyd. DM-?-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.
Keywords: Celecoxib; 2,6-di-O-Methyl-?-cyclodextrin; Chemical?physical characterization; Permeation through CaCo-2 cells
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