Meyer, Dominique,Corot, Claire,Port, Marc,Barbotin, Vincent,Bonnemain, Bruno
申请号：
ES14165006
公开号：
ES2597782T3
申请日:
2009.02.18
申请国别(地区):
ES
年份:
2017
代理人:
摘要：
Process for preparing a liquid pharmaceutical formulation containing a complex of macrocyclic chelate with a lanthanide and mol / mol amount of free macrocyclic chelate of between 0.002% and 0.4%, said process comprising the following successive steps: b) preparation of a liquid pharmaceutical composition containing the complex of macrocyclic chelate with a lanthanide, and chelate free macrocyclic that is not in the form of an X excipient [X , L] in which L is the macrocyclic chelate and X and X are a metal ion, in particular chosen independently from calcium, sodium, zinc and magnesium and / or free lanthanide mixing a solution of free DOTA as free macrocyclic chelate and of free gadolinium and free lanthanide, for complexation lanthanide by macrocyclic chelate, the amounts of free macrocyclic lanthanide chelate and free such that all the lanthanide is complexed and Cch l> Ct ch l, representing Cch l concentration macrocyclic chelate and of free Ct ch l representing the target concentration of free macrocyclic chelate in the final liquid pharmaceutical formulation, wherein Ct ch l selected in the range of between 0.002% and 0.4% mol / mol c) measurement in the pharmaceutical formulation obtained in step b) of Cch l the concentration of free lanthanide Clan l equal to 0 d) setting Cch l of Clan l removing free macrocyclic chelate and / or adding lanthanide free and / or changing the pH of the formulation obtained in step b) to obtain Cch l> = Ct ch l Clan l> = 0 wherein Ct ch l is the target concentration of free macrocyclic chelate in the final liquid pharmaceutical formulation and is selected in the range of between 0.002% and 0.4% mol / mol, wherein the amount of macrocyclic chelate free in the final liquid pharmaceutical formulation corresponds to the proportion of free macrocyclic chelate relative to the amount of macrocyclic chelate DOTA-Gd uncomplexed in the final liquid pharmaceutical formulation mol / mol, wherein the macrocyclic chelate is DOTA and the la
