Preparation and characterization of amorphous ciprofloxacin-amino acid salts

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.

Fluoroquinolone Amorphous Polymeric Salts and Dispersions for Veterinary Uses

“…Amorphous salts of CIP containing succinic acid or amino acids as counterions have also been prepared. While these formulations were far more soluble than the CIP ASDs, they were less stable when exposed to high humidity and in most cases decreased the permeability of the drug [10,11].…”

Permeability of glibenclamide through a PAMPA membrane: The effect of co-amorphization

“…The permeability properties of a drug compound through artificial or cell membranes are generally determined by dissolving the drug into the testing medium at a predetermined concentration and then measuring the Papp, i.e. the apparent permeability coefficient [10][11][12]. However, this experimental setup does not determine the interplay between drug (or formulation) dissolution properties and permeation.…”

Sacharides and their derivatives as pharmaceutical additives

“…pozytywne wyniki badań dotyczące istotnego wpływu substancji pomocniczych na stabilność różnych preparatów zaobserwowano również dla związków powierzchniowo czynnych, cukrów oraz makrocząsteczek, takich jak peptydy i liposomy czy cyklodekstryny [4,5,6,7]. W technologii postaci leku wykorzystuje się różne związki chemiczne jako substancje pomocnicze, jednak od dawna szeroko rozpowszechnione są cukry i pochodne cukrowe.…”