PMID- 16527440
OWN - NLM
STAT- MEDLINE
DCOM- 20060801
LR  - 20151119
IS  - 0731-7085 (Print)
IS  - 0731-7085 (Linking)
VI  - 41
IP  - 3
DP  - 2006 Jun 7
TI  - Sildenafil/cyclodextrin complexation: stability constants, thermodynamics, and 
      guest-host interactions probed by 1H NMR and molecular modeling studies.
PG  - 857-65
AB  - Guest-host interactions of sildenafil (Sild) with cyclodextrins (CyDs) have been 
      investigated using several techniques including phase solubility diagrams (PSD), 
      differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), 
      proton nuclear magnetic resonance (1H NMR) and molecular mechanical modeling 
      (MM+). Estimates of the complex formation constant (K11) show that the tendency 
      of Sild to complex with CyDs follows the order: beta-CyD>HP-beta-CyD>gamma-CyD, 
      alpha-CyD, where K11 values at pH 8.7 and 30 degrees C were 150, 68 and 46, 43 
      M-1, respectively. Ionization of Sild reduces its tendency to complex with 
      beta-CyD, where protonated (at pH 3.6) and anionic Sild (at pH 12.1) species have 
      K11 values of 17 and 42 M-1, respectively, compared with 150 M-1 for neutral Sild 
      (at pH 8.7). The hydrophobic character of Sild was found to provide 39% of the 
      driving force for complex stability, while other factors including specific 
      interactions contribute -7.9 kJ/mol. Complex formation of Sild with beta-CyD 
      (DeltaG degrees=-22.9 kJ/mol) is largely driven by enthalpy (DeltaH degrees=-19.8 
      kJ/mol) and slight entropy (DeltaS degrees=10.3 J/molK) changes. 1H NMR and MM+ 
      studies indicate formation of two isomeric 1:1 complexes: one involving complete 
      inclusion of the phenyl-moiety into the beta-CyD cavity while the other 
      pertaining to partial inclusion of the pyrimidinone moiety. The dominant driving 
      force for complexation is evidently van der Waals with very little electrostatic 
      contribution. DSC, XRPD and 1H NMR studies proved the formation of inclusion 
      complex in solution and the solid state.
FAU - Al Omari, Mahmoud M
AU  - Al Omari MM
AD  - The Jordanian Pharmaceutical Manufacturing Company, Naor, Jordan. 
      momari@jpm.com.jo
FAU - Zughul, Mohammad B
AU  - Zughul MB
FAU - Davies, J Eric D
AU  - Davies JE
FAU - Badwan, Adnan A
AU  - Badwan AA
LA  - eng
PT  - Journal Article
DEP - 20060309
PL  - England
TA  - J Pharm Biomed Anal
JT  - Journal of pharmaceutical and biomedical analysis
JID - 8309336
RN  - 0 (Cyclodextrins)
RN  - 0 (Piperazines)
RN  - 0 (Protons)
RN  - 0 (Purines)
RN  - 0 (Sulfones)
RN  - BW9B0ZE037 (Sildenafil Citrate)
SB  - IM
MH  - Calorimetry, Differential Scanning
MH  - Cyclodextrins/*chemistry
MH  - Magnetic Resonance Spectroscopy/*methods
MH  - *Models, Molecular
MH  - Piperazines/*chemistry
MH  - Protons
MH  - Purines
MH  - Sildenafil Citrate
MH  - Spectrophotometry, Ultraviolet
MH  - Sulfones
MH  - Thermodynamics
MH  - X-Ray Diffraction
EDAT- 2006/03/11 09:00
MHDA- 2006/08/02 09:00
CRDT- 2006/03/11 09:00
PHST- 2005/08/24 00:00 [received]
PHST- 2006/01/26 00:00 [revised]
PHST- 2006/01/29 00:00 [accepted]
PHST- 2006/03/11 09:00 [pubmed]
PHST- 2006/08/02 09:00 [medline]
PHST- 2006/03/11 09:00 [entrez]
AID - S0731-7085(06)00128-2 [pii]
AID - 10.1016/j.jpba.2006.01.055 [doi]
PST - ppublish
SO  - J Pharm Biomed Anal. 2006 Jun 7;41(3):857-65. doi: 10.1016/j.jpba.2006.01.055. 
      Epub 2006 Mar 9.