Abstract:
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.