Interaction of Valdecoxib with Beta Cyclodextrin: Experimental and Molecular Modeling Studies

Jadhav, Ganesh S., Patel, Ashok R., Vavia, Pradeep R., Malde, Alpeshkumar K. and Coutinho, Evans C. (2005). Interaction of Valdecoxib with Beta Cyclodextrin: Experimental and Molecular Modeling Studies. In: Journal of Inclusion Phenomenon and Macrocyclic Chemistry: Proceedings of the 3rd Asian Cyclodextrin Conference (ACC2005). 3rd Asian Cyclodextrin Conference (ACC2005), Tianjin, China, (261-273). 8-12 May, 2005. doi:10.1007/s10847-006-9093-2


Author Jadhav, Ganesh S.
Patel, Ashok R.
Vavia, Pradeep R.
Malde, Alpeshkumar K.
Coutinho, Evans C.
Title of paper Interaction of Valdecoxib with Beta Cyclodextrin: Experimental and Molecular Modeling Studies
Conference name 3rd Asian Cyclodextrin Conference (ACC2005)
Conference location Tianjin, China
Conference dates 8-12 May, 2005
Proceedings title Journal of Inclusion Phenomenon and Macrocyclic Chemistry: Proceedings of the 3rd Asian Cyclodextrin Conference (ACC2005)   Check publisher's open access policy
Journal name Journal of Inclusion Phenomena and Macrocyclic Chemistry   Check publisher's open access policy
Place of Publication Dordrecht ; Boston
Publisher Kluwer Academic Publishers
Publication Year 2005
Sub-type Fully published paper
DOI 10.1007/s10847-006-9093-2
ISSN 0923-0750
Volume 56
Issue 1-2
Start page 261
End page 273
Total pages 13
Language eng
Abstract/Summary This study aimed to investigate the effect of β-cyclodextrin on aqueous solubility and dissolution rate of valdecoxib and also to get an insight of molecular interactions involved in formation of valdecoxib‐β-cyclodextrin inclusion complex. Phase solubility analysis indicated complex with possible stoichiometry of 1:1 and a stability constant of 234.01 M−1. Thermodynamic studies in water indicated exothermic nature of inclusion complexation.␣Valdecoxib‐β-cyclodextrin complexes (1:1 M) were prepared by kneading method, solution method and␣freeze–drying method. The complex was characterized by differential scanning calorimetry (DSC), powder X-ray diffractometry (P-XRD), Fourier transform infrared (FTIR) spectroscopy and nuclear magnetic resonance␣(1H-NMR) spectroscopy. Molecular modeling was used to help establish the mode of interaction of β-cyclodextrin with valdecoxib. 1H-NMR analysis suggested that the unsubstituted phenyl ring of valdecoxib display favorable interaction with the hydrophobic cavity of β-cyclodextrin, which was confirmed by molecular dynamic simulations. An inclusion complex model has been established for explaining the observed enhancement of solubility of valdecoxib in water by β-cyclodextrin. Dissolution studies in water showed that the valdecoxib in freeze-dried complex dissolved much faster than the uncomplexed drug and physical mixture. This improvement in dissolution rate is attributed to the increased solubility and wettability due to encapsulation along with decreased crystallanity caused by complex formation, which is evident by DSC and P-XRD studies.
Subjects 030499 Medicinal and Biomolecular Chemistry not elsewhere classified
030799 Theoretical and Computational Chemistry not elsewhere classified
Keyword β-cyclodextrin
complexation
dissolution studies
molecular modeling
solubility
valdecoxib
Q-Index Code EX

 
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