Complexation of celecoxib with β‐cyclodextrin: Characterization of the interaction in solution and in solid state

Abstract

Inclusion complexation between celecoxib, a specific cyclooxygenase II inhibitor, and beta‐cyclodextrin (β‐CD) was studied in solution and solid state. Drug cyclodextrin complexes were prepared by spray drying while physical mixtures were obtained by simple blending. Inclusion complexes were characterized by nuclear magnetic resonance spectroscopy (NMR), differential scanning calorimetry (DSC), X‐ray diffractometry (XRD), scanning electron microscopy (SEM), infrared spectroscopy (IR), and polarimetry. Phase solubility analysis was carried out to determine the stability constant. Solubility studies revealed the existence of a 1:1 complex between celecoxib and β‐CD. NMR studies suggested a strong interaction between celecoxib and β‐CD prepared by spray drying. XRD and SEM analysis illustrated that celecoxib existed as an amorphous complexed form in spray‐dried complexes. Dissolution studies showed that the celecoxib entrapped in spray‐dried complexes dissolved much faster than the uncomplexed drug and physical mixtures. The data obtained suggest that celecoxib forms an inclusion complex with β‐CD in solution and solid state, which was confirmed by various analytical techniques. A shorter t50% of dissolution is found for the formulation prepared by spray drying when compared on a weight basis in a USP II apparatus. © 2005 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:676–687, 2005