?-Cyclodextrin Complexes of Celecoxib: Molecular-Modeling, Characterization, and Dissolution Studies

?-Cyclodextrin Complexes of Celecoxib: Molecular-Modeling, Characterization, and Dissolution Studies
March 2004
M. Narender Reddy, Tasneem Rehana, S. Ramakrishna, K. P. R. Chowdary, and Prakash V. Diwan
AAPS PharmSci 2004; 6 (1) Article 7
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Abstract
Celecoxib, a specific inhibitor of cycloxygenase-2 (COX-2) is a poorly water-soluble nonsteroidal anti-inflammatory drug with relatively low bioavailability. The effect of ?-cyclodextrin on the aqueous solubility and dissolution rate of celecoxib was investigated. The possibility of molecular arrangement of inclusion com-plexes of celecoxib and ?-cyclodextrin were studied us-ing molecular modeling and structural designing. The results offer a better correlation in terms of orientation of celecoxib inside the cyclodextrin cavity. Phase-solubility profile indicated that the solubility of celecoxib was sig-nificantly increased in the presence of ?-cyclodextrin and was classified as AL-type, indicating the 1:1 stoichiometric inclusion complexes. Solid complexes prepared by freeze drying, evaporation, and kneading methods were characterized using differential scanning calorimetry, powder x-ray diffractometry, and scanning electron microscopy. In vitro studies showed that the solubility and dissolution rate of celecoxib were signifi-cantly improved by complexation with ?-cyclodextrin with respect to the drug alone. In contrast, freeze-dried complexes showed higher dissolution rate than the other complexes.