Cyclodextrin complexes of valdecoxib: properties and anti-inflammatory activity in rat.
The influence of natural beta-cyclodextrin and its hydrophilic derivatives (HPbetaCd and SBE7betaCd) on the in vitro dissolution rate, in vivo absorption and oral bioavailability of a poorly water soluble anti-inflammatory agent, valdecoxib (VALD) was studied. Equimolar drug-cyclodextrin solid complexes were prepared by kneading and coevaporation methods and characterized by infrared spectroscopy, differential scanning calorimetry, X-ray diffraction. In the liquid state, the cyclodextrin complexes were studied using phase solubility analysis, (1)H nuclear magnetic resonance and circular dichroism spectroscopy. Drug solubility and dissolution rate in distilled water were notably improved by employing the betaCds. The DP(15) (i.e. percent of dissolved VALD at 15 min) was 10.5% for the pure drug and 50, 91 and 93% for VALD-betaCd, VALD-HPbetaCd and VALD-SBE7betaCd complexes, respectively. Moreover, it was found that in the, the cyclodextrin complexes of drug showed significant improvement in the anti-inflammatory activity.
Rajendrakumar
Kale
K
Department of Pharmaceutics, Bombay college of Pharmacy, Kalina, Santacruz (E), Mumbai, India.
Madhusudan
Saraf
S
Pralhad
Tayade
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000737:chemistry / Q000494:pharmacology*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002942:Circular Dichroism; D003505:Cyclodextrins / Q000737:chemistry*; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005079:Excipients; D007555:Isoxazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D051381:Rats; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013449:Sulfonamides / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D014961:X-Ray Diffraction; D000096926:Benzenesulfonamides
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003505:Cyclodextrins; D005079:Excipients; D007555:Isoxazoles; D013449:Sulfonamides; C406224:valdecoxib; D000096926:Benzenesulfonamides