Gadobenate dimeglumine 0.5 M solution for injection (MultiHance (R)): Pharmaceutical formulation and physicochemical properties of a new magnetic resonance imaging contrast medium

Objective: To characterize the proton-magnetic relaxation properties and co mplexation equilibria of gadobenate dimeglumine and to develop a pharmaceut ical formulation for injection. Methods: Proton-magnetic relaxivities were determined at 20 MHz and 39 degr ees C. Metal complexation was studied potentiometrically. Degradation pathw ays were identified through prolonged exposure to elevated temperature. Results: Because of its size and very weak interaction with serum albumin, gadobenate dimeglumine has proton-magnetic relaxivities that are larger tha n those of gadopentetate dimeglumine in both water and biological fluids. W ith regard to metal complexation, the two products are indistinguishable. T he metal complexation behavior and thermal stability of the product allowed a pharmaceutical formulation for injection containing 0.5 M gadobenate dim eglumine without excipients. The physicochemical properties of the formulat ed product were determined. Conclusion: Gadobenate dimeglumine has an elevated T-1-relaxivity, especial ly in blood plasma. The high stability of the complex guarantees a negligib le release of gadolinium ion. Gadobenate dimeglumine 0.5 Mi solution for in jection has a shelf life of three years.