Gadobenate Dimeglumine 0.5 M Solution for Injection (MultiHance®): Pharmaceutical Formulation and Physicochemical Properties of a New Magnetic Resonance Imaging Contrast Medium

Abstract

To characterize the proton-magnetic relaxation properties and complexation equilibria of gadobenate dimeglumine and to develop a pharmaceutical formulation for injection. Proton-magnetic relaxivities were determined at 20 MHz and 39°C. Metal complexation was studied potentiometrically. Degradation pathways were identified through prolonged exposure to elevated temperature. Because of its size and very weak interaction with serum albumin, gadobenate dimeglumine has proton-magnetic relaxivities that are larger than those of gadopentetate dimeglumine in both water and biological fluids. With regard to metal complexation, the two products are indistinguishable. The metal complexation behavior and thermal stability of the product allowed a pharmaceutical formulation for injection containing 0.5 M gadobenate dimeglumine without excipients. The physicochemical properties of the formulated product were determined. Gadobenate dimeglumine has an elevated T1-relaxivity, especially in blood plasma. The high stability of the complex guarantees a negligible release of gadolinium ion. Gadobenate dimeglumine 0.5 M solution for injection has a shelf life of three years.