In vitro and in vivo evaluation of clarithromycin-urea solid dispersions prepared by solvent evaporation, electrospraying and freeze drying methods

Abstract

Clarithromycin, a poorly water soluble drug, is a new broad spectrum macrolide antibiotic, used in many infections. The objective of the present study was to prepare clarithromycin-urea solid dispersions, with a view to improve the drug dissolution rate and oral bioavailability. The solid dispersions were prepared by solvent evaporation, electrospraying and freeze drying methods in 3 different ratios of drug to urea. Physicochemical properties of the prepared solid dispersions were evaluated as well. Scanning electron microscopic images showed that the microscale size crystals were obtained by freeze drying method. All the solid dispersions showed faster drug release in comparison with pure clarithromycin. Differential scanning calorimetry as well as X-ray powder diffractions showed reduced drug crystallinity in the solid dispersions. Fourier-transform infrared spectroscopy demonstrated hydrogenic bond between - NH and C=O groups of urea with - OH, -O- and C=O groups of clarithromycin. Oral pharmacokinetic studies in the rabbits revealed an improved bioavailability of the solid dispersions in comparison with that of pure clarithromycin powder. Moreover, pharmacokinetic study showed a decrease in inter-individual variation of the oral bioavailability. (C) 2014 Elsevier B.V. All rights reserved.