Cyclodextrin inclusion complexes of the central analgesic drug nefopam.
Inclusion complexes of nefopam base (NEF) with various beta-cyclodextrins (betaCDs) were investigated. All tested betaCDs increased the apparent solubility of NEF according to a Higuchi AL type plot (except betaCD: AN type plot), which indicates the formation of 1:1 stoichiometry inclusion complexes. 1H-NMR and 13C-NMR experiments showed that complexation by CDs allowed an easy separation of the R and S enantiomers. Based on spectral data obtained from the two-dimensional rotating frame nuclear Overhauser effect spectroscopy (2D-ROESY), a reasonable geometry for the complexes could be proposed implicating the insertion of the benzoxazocine ring into the wide end of the torus cavity.
Brun
H
H
Laboratoire de Pharmacotechnie, Service de Pharmacie, Hôpital Henri Mondor, Créteil, France.
Paul
M
M
Razzouq
N
N
Binhas
M
M
Gibaud
S
S
Astier
A
A
D000286:Administration, Sublingual; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001682:Biological Availability; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008958:Models, Molecular; D009340:Nefopam / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D019906:Nuclear Magnetic Resonance, Biomolecular; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism; D014867:Water; D047392:beta-Cyclodextrins / Q000008:administration & dosage*
D018712:Analgesics, Non-Narcotic; D046911:Macromolecular Substances; D047392:beta-Cyclodextrins; D014867:Water; D009340:Nefopam