Beta-cyclodextrin complexes of celecoxib: molecular-modeling, characterization, and dissolution studies.
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 beta-cyclodextrin on the aqueous solubility and dissolution rate of celecoxib was investigated. The possibility of molecular arrangement of inclusion complexes of celecoxib and beta-cyclodextrin were studied using 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 significantly increased in the presence of beta-cyclodextrin and was classified as A(L)-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 significantly improved by complexation with beta-cyclodextrin with respect to the drug alone. In contrast, freeze-dried complexes showed higher dissolution rate than the other complexes.
Reddy
M Narender
MN
Pharmacology Division, Indian Institute of Chemical Technology, Hyderabad, India-500007.
Rehana
Tasneem
T
Ramakrishna
S
S
Chowdhary
K P R
KP
Diwan
P V
PV
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D000068579:Celecoxib; D003505:Cyclodextrins / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D008958:Models, Molecular; D011208:Powders / Q000737:chemistry; D011487:Protein Conformation; D011720:Pyrazoles; D012995:Solubility; D013449:Sulfonamides / Q000737:chemistry*; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003505:Cyclodextrins; D011208:Powders; D011720:Pyrazoles; D013449:Sulfonamides; D047392:beta-Cyclodextrins; D000068579:Celecoxib; C031215:betadex