MICROBIOLOGICAL AND PHYSICOCHEMICAL STUDIES OF KETOKONAZOLE:b-CYCLODEXTRIN:CITRIC ACID MULTICOMPONENT INCLUSION COMPOUNDS

ZOPPI A; AIASSA V; BRUNO A; LONGHI MR

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

SAFE

Candida is an opportunistic yeast that causes severediseases in immunocompromised individuals. Ketoconazole (KET)is an antifungal agent suitable for the treatment of candidiasis andother systemic fungal infections, classified as a class II drug in theBiopharmaceutics Classification System because of its low solubilityand high permeability. Cyclodextrins (CD) multicomponent complexationis used to improve the poor aqueous solubility of differentdrugs. As citric acid (CA) is a pH-modifier used to increase solubilityof weakly basic compounds, the aim of this work was to assess theeffect of KET:βCD:CA multicomponent complexation in the solubilityand antifungal activity of KET.The effects of complexation on drug solubility, was determined inwater, by means of phase-solubility studies. In solid state, the multicomponentsystems, prepared by physical mixture (PM) or kneading(K), were studied by Fourier-transform infrared spectroscopy, thermalanalysis and scanning electron microscopy. The microbiologicalactivity was evaluated by the agar diffusion test.The presence of βCD and CA caused a significantly increase inKET solubility with S0 of 0.542 μg/ml in water, 2.6 mg/ml in presenceof CA (10 mM) and Smax of 3.8 mg/ml with CA and βCD (13.2 mM).Taking into account the results obtained by the different techniquesin solid state, it is possible to confirm the formation of inclusion complexbetween KET and βCD in presence of CA, in systems preparedby K. The PM shows a behaviour comparable with the pure compounds.Furthermore, the antifungal activity against Candida albicansy C.parapsilosis was significantly improved (p