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Application of Fluorescence Emission for Characterization of Albendazole and Ricobendazole Micellar Systems: Elucidation of the Molecular Mechanism of Drug Solubilization Process

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Abstract

Albendazole (ABZ) and ricobendazole (RBZ) are referred to as class II compounds in the Biopharmaceutical Classification System. These drugs exhibit poor solubility, which profoundly affects their oral bioavailability. Micellar systems are excellent pharmaceutical tools to enhance solubilization and absorption of poorly soluble compounds. Polysorbate 80 (P80), poloxamer 407 (P407), sodium cholate (Na-C), and sodium deoxycholate (Na-DC) have been selected as surfactants to study the solubilization process of these drugs. Fluorescence emission was applied in order to obtain surfactant/fluorophore (S/F) ratio, critical micellar concentration, protection efficiency of micelles, and thermodynamic parameters. Systems were characterized by their size and zeta potential. A blue shift from 350 to 345 nm was observed when ABZ was included in P80, Na-DC, and Na-C micelles, while RBZ showed a slight change in the fluorescence band. P80 showed a significant solubilization capacity: S/F values were 688 for ABZ at pH 4 and 656 for RBZ at pH 6. Additionally, P80 micellar systems presented the smallest size (10 nm) and their size was not affected by pH change. S/F ratio for bile salts was tenfold higher than for the other surfactants. Quenching plots were linear and their constant values (2.17/M for ABZ and 2.29/M for RBZ) decreased with the addition of the surfactants, indicating a protective effect of the micelles. Na-DC showed better protective efficacy for ABZ and RBZ than the other surfactants (constant values 0.54 and 1.57/M, respectively), showing the drug inclusion into the micelles. Entropic parameters were negative in agreement with micelle formation.

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Acknowledgements

J.P. is grateful to the CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas) for a Doctoral Fellowship. This work was supported by the Universidad Nacional de Rosario, CONICET (Project No. PIP 112-201001-00194) and Agencia Nacional de Promoción Científica y Tecnológica (Project No. PICT 2006-1126). The authors would like to thank Laura Gutierrez and Antonella Giorello from Facultad de Ingeniería Química, Universidad Nacional del Litoral, for Malvern Zetasizer Nano ZS90. We would like to thank the staff from the English Department (Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario) for the language correction of the manuscript.

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Correspondence to María C. Lamas.

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Priotti, J., Leonardi, D., Pico, G. et al. Application of Fluorescence Emission for Characterization of Albendazole and Ricobendazole Micellar Systems: Elucidation of the Molecular Mechanism of Drug Solubilization Process. AAPS PharmSciTech 19, 1152–1159 (2018). https://doi.org/10.1208/s12249-017-0927-6

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