Cyclodextrin Inclusion Complexes of the Central Analgesic Drug Nefopam

ABSTRACT

Inclusion complexes of nefopam base (NEF) with various β‐cyclodextrins (βCDs) were investigated. All tested βCDs increased the apparent solubility of NEF according to a Higuchi A_L type plot (except βCD: A_N 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.

KEYWORDS:

• Nefopam
• Cyclodextrins
• Solubility diagram
• MNR
• ROESY