Theoretical and experimental investigations of organic acids/cyclodextrin complexes and their consequences upon the formation of miconazole/cyclodextrin/acid ternary inclusion complexes.
(1)H NMR spectrometry, FT-IR spectroscopy, as well as molecular modeling at the AM1 level and normal mode analysis were used to characterise the interactions and the formation of inclusion complexes between three organic acids: maleic, fumaric, L-tartaric acids and betaCD. In aqueous medium, the complexation was confirmed by (1)H NMR spectroscopy using two-dimensional technique. The stable geometries of the complexes were determined by molecular modeling. Experimental infrared frequencies were assigned on the base of the vibrational normal mode calculation at the fully optimized geometry for the inclusion complexes. All the results point out the presence of stable inclusion complexes between acids and betaCD at the solid state. These results show the double role of the acid. Correlated with the theoretical and experimental data previously obtained for the miconazole/CD/acids complexes, in function of both acids and CDs structures, the acids can either stabilize the complexes by formation of a multicomponent complex or form acid/CD inclusion complexes, hindering the guest inclusion.
Barillaro
Valéry
V
Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Liege, B-4000 Liège, Belgium. v.barillaro@gmail.com
Dive
Georges
G
Bertholet
Pascal
P
Evrard
Brigitte
B
Delattre
Luc
L
Frederich
Michel
M
Ziémons
Eric
E
Piel
Geraldine
G
D003998:Dicarboxylic Acids / Q000737:chemistry*; D005650:Fumarates / Q000737:chemistry; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008298:Maleates / Q000737:chemistry; D008825:Miconazole / Q000737:chemistry*; D008958:Models, Molecular; D014677:Pharmaceutical Vehicles / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013644:Tartrates / Q000737:chemistry; D013816:Thermodynamics; D047392:beta-Cyclodextrins / Q000737:chemistry*
D003998:Dicarboxylic Acids; D005650:Fumarates; D008298:Maleates; D014677:Pharmaceutical Vehicles; D013644:Tartrates; D047392:beta-Cyclodextrins; D008825:Miconazole; C032005:fumaric acid; C030272:maleic acid; C031215:betadex; C029768:tartaric acid