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Journal of Biomaterials Applications
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Preparation and Characterization of the Inclusion Complex of Furosemide with Hydroxypropyl-ß-Cyclodextrin

Marilena Vlachou

Department of Pharmaceutical Technology, School of Pharmacy, University of Athens, Panepistimiopolis, 15771 Zografou, Athens, Greecevlachou{at}pharm.uoa.gr

George Papaïoannou

Department of Pharmaceutical Technology, School of Pharmacy, University of Athens, Panepistimiopolis, 15771 Zografou, Athens, Greece

A highly hydrophobic drug, furosemide, was treated with 2-Hydroxypropyl-ß-Cyclodextrin in an attempt to produce modified compounds with increased water solubility. Following a freeze-drying process, the interactions of furosemide and cyclodextrin led to the formation of an inclusion complex, whose dissolution rate in water was studied by the solubility method. Furthermore, mechanical mixtures of furosemide and cyclodextrin were also prepared and tested for their solubility. The reaction products were characterized in the solid state by differential scanning calorimetry (DSC), which provided some evidence about complexation. Additional evidence was obtained by recording the 1HNMR spectra of aqueous solutions of these same products. The study of phase solubility was based on the Higuchi & Connors method and showed an impressive enhancement of the miscibility of furosemide with water. In fact, a 11 fold increase of the drug solubility was recorded for the inclusion complex, in the first stages of dissolution. The experimental results of this work show that 2-Hydroxypropyl-ß-Cyclodextrin isan efficient complexation agent for furosemide. Combination of those two substances can be carried out by simple techniques, providing easy control and the obtained inclusion complex is characterized by acceptable water solubility and increased dissolution rate.

Key Words: furosemide • 2-Hydroxypropyl–ß–Cyclodextrin • complexation • dissolution • characterization • freeze-drying process

Journal of Biomaterials Applications, Vol. 17, No. 3, 197-206 (2003)
DOI: 10.1177/0885328203017003557
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