Patent ID: 9636427
Date: 2017-05-02
CPC Classifications: A61K,A61P,G01N

Claim:
1. An industrial process for preparing a liquid pharmaceutical formulation containing a complex of macrocyclic chelate with a lanthanide and a mol/mol amount of free macrocyclic chelate between 0.002% and 0.4%, said process comprising the following successive steps: b) preparing a liquid pharmaceutical formulation containing a complex of macrocyclic chelate with a lanthanide, and: free macrocyclic chelate, and optionally free lanthanide; c1) adjusting the pH of a sample of the liquid pharmaceutical formulation obtained in step b) so that the concentration of free lanthanide C c2) measuring, in the sample of the liquid pharmaceutical formulation obtained in step c1), the concentration of free macrocyclic chelate C d) adjusting C wherein the amount of free macrocyclic chelate in the final liquid pharmaceutical formulation corresponds to the proportion of free macrocyclic chelate relative to the amount of complexed macrocyclic chelate DOTA-Gd in the final liquid pharmaceutical formulation in mol/mol, wherein the macrocyclic chelate is DOTA and the lanthanide is gadolinium, and wherein steps b) and d) of the process occur in the same reactor, and wherein the liquid pharmaceutical formulation is an injectable solution.