Preparation and characterization of amorphous ciprofloxacin-amino acid salts

The amorphization of the poorly soluble drug ciprofloxacin (CIP) may be facilitated by the use of a suitable stabilizer. In this study seven amino acids, with various side chain properties, were evaluated in this regard. Solid dispersions were prepared by ball milling 1:1 molar ratios of CIP with the amino acids, and their solid-state and pharmaceutical properties were then examined. Fully X-ray amorphous solid dispersions were obtained with aspartic acid, glutamic acid, cysteine and arginine. In each case, evidence of salt formation between the drug and amino acids was found via Fourier transform infrared spectroscopy and solid-state nuclear magnetic resonance. In contrast, semi-crystalline solid dispersions were obtained with serine, alanine and glycine. The glass transition temperatures of the amorphous salts were significantly higher than those of the starting materials, and they remained fully X-ray amorphous during long-term stability studies. Significant improvements in the solubility of CIP were also observed with the amorphous salts in water and simulated biological fluids, over and above that of the corresponding physical mixtures. In permeability studies on the other hand, the amorphous aspartate and glutamate salts were found to be less permeable than the pure drug, whereas formulation as an amorphous salt containing cysteine or arginine increased the permeability of CIP. Therefore, while amorphous salt formation with amino acids appears to be a suitable means of improving the thermal stability and solubility of CIP, in some cases this is associated with a decrease in permeability.