INCLUSION OF MICONAZOLE INTO CYCLODEXTRINS BY MEANS OF SUPERCRITICAL CARBON DIOXIDE: INFLUENCE OF THE ADDITION OF AN ACIDIC TERNARY COMPOUND

摘要

By means of supercritical carbon dioxide, inclusion complexes can be obtained at the solid state. In this paper, inclusion complexes formed between miconazole, an antifungal drug with a basic character and a poor aqueous solubility, and several cyclodextrins are studied. The experiments were performed with both miconazole base and nitrate. The physical mixture was processed with supercritical carbon dioxide at 125℃ and 30 MPa during 60 minutes. The influence of the addition of an acidic ternary compound (citric acid, fumaric acid, maleic acid and malic acid) has been evaluated. The inclusion yields are measured by the differential solubility method and by an HPLC method. The results show that miconazole base gives better inclusion yields than miconazole nitrate. The use of both an hydroxypropyl cyclodextrin derivatives and an acidic ternary compound enhances the inclusion yield.