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Wednesday 01 February 2006

Griseofulvin and ketoconazole solubilization by bile salts studied using fluorescence spectroscopy.

By: Calafato NR, Pico G.

Colloids Surf B Biointerfaces 2006 Feb 1;47(2):198-204

The capacity of solubilization of the five physiological bile salts: cholate, deoxicholate, hiocholate, quenodeoxicholate and taurocholate were assayed on two low aqueous soluble antimicotic agents: griseofulvin and ketoconazole. The fluorescence emission of these antimicotic agents was used as tool to study their solubilization in bile salts micelle. Griseofulvin enhanced its fluorescence and shifted to the blue in the presence of bile salts micelles. The shift was dependent of the polarizability of the micelle zone where the antimicotic is located. Cholate and deoxicholate showed a good solubilization capacity for griseofulvin: 321 mol and 394 mol surfactant per mol of antimicotic, respectively. These values decreased in the presence of NaCl in agreement with a compactness of the micelle due to an electrostatic repulsion decreasing between the bile salts monomer negatively charged. The imidazole and piperazine rings present in the ketoconazole molecule give to this the capacity of fluorescence emission with two vibronic bands at 364 nm and 382 nm, respectively. The solubilization in cholate micelle induced an increase in the band at 382 nm, while deoxicholate induced the opposite effect, suggesting a strong intercation between the polar groups of ketoconazole molecule (imidazole and piperazine rings) and the (-)OH of these bile salts. The solubilization capacities were 47 mol and 117 mol surfactant per ketoconazole mol for cholate and deoxicholate, respectively. The other bile salts assayed did not show any appreciable solubilization capacity. Ketoconazole and griseofulvin solubilized in micelles of cholate and deoxicholate were stable during the thermal recycling treatment for over 100 days.

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