Investigation and physicochemical characterization of clarithromycin-citric acid-cyclodextrins ternary complexes

The purpose of this study was to investigate the effect of citric acid (CA) on the complexation of clarithromycin (CLM) with beta-cyclodextrin (betaCD) in aqueous solutions and in the solid state. A phase solubility study revealed a positive effect of CA on the drug solubility. A B(s)-type solubility with an apparent stability constant (K(c)) of 102.4 M(-1) was obtained for CLM in betaCD solution and 161.2 M(-1) for CLM in 6 mM betaCD solution. Solid ternary complexes were prepared by coevaporation and lyophilization. CLM-betaCD-CA interactions were studied in the solid state by differential scanning calorimetry (DSC), infrared spectroscopy, scanning electron microscopy and X-ray diffractometry. A part of the guest molecule was located in the betaCD host cavity. The results obtained suggest that the lyophilization method yields a higher degree of amorphous entity than coevaporation.