Effect of acidic ternary compounds on the formation of miconazole/cyclodextrin inclusion complexes by means of supercritical carbon dioxide.
OBJECTIVE
The aim of the study is to evaluate the effect of different acidic compounds on the inclusion of miconazole (MICO) in several cyclodextrins (CDs) using supercritical carbon dioxide (SCCO(2) ) processing.


METHODS
Physical mixtures were processed by SCCO(2) at 30 MPa, 125 degrees C during 60 minutes in a static mode to produce inclusion complexes. The inclusion complexes were characterized by differential solubility, Fourier transform infrared spectroscopy (FT-IR) and dissolution test.


RESULTS
The best inclusion yields were achieved with the combination of MICO base and HPgammaCD with or without acids. Maleic and fumaric acids influenced the MICO inclusion differently in function of their conformation. During the process, a miconazole salt was observed with maleic acid and characterized by thermal analysis and mass spectrometry. The kinetics inclusion followed a saturation-type shape curve. FT-IR confirmed the presence of genuine inclusion complexes. The complexes MICO base/HPgammaCD/(L-tartaric acid) enhanced the dissolution rates of MICO more than the corresponding physical mixtures did. Lastly, the stability study revealed that the complexes were stable.


CONCLUSIONS
The formation of stable complexes between MICO and CDs is possible using SCCO(2). Moreover an acidic ternary compound is able to modify the formation of the complex. The inclusion complexes, which show better dissolution profiles than those with the corresponding physical mixtures, could lead to an increase of the oral bioavailability of MICO.
Barillaro
Valéry
V
Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Liège, CHU-Tour 4, Bat. B36, Avenue de l'Hôpital, 1, 4000 Liège 1, Belgium. v.barillaro@ulg.ac.be <v.barillaro@ulg.ac.be>
Bertholet
Pascal
P
Henry de Hassonville
Sandrine
S
Ziemon
Eric
E
Evrard
Brigette
B
Delattre
Luc
L
Piel
Géraldine
G
D002245:Carbon Dioxide / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003505:Cyclodextrins / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008825:Miconazole / Q000737:chemistry*
D003505:Cyclodextrins; D002245:Carbon Dioxide; D008825:Miconazole