Process for producing a contrast agent
AssigneeSanochemia Pharmazeutika AG
InventorsStefan Welzig, Beate Kälz, József Gungl, Klaus Gerdes, Roswitha Braunrath, Christina Abrahamsberg
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Abstract
Disclosed is a process for producing a contrast agent-containing pharmaceutical preparation, which contains as the contrast agent a complex of a lanthanide, in particular gadolinium, and a macrocyclic chelate, in particular DOTA.
Claims15
A method for producing an aqueous liquid preparation containing, as contrast agent for magnetic resonance, a complex of a lanthanide and a macrocyclic chelate, the preparation containing free macrocyclic chelate, the method comprising:
- a) dissolving a macrocyclic chelate in water,
- b) adding a lanthanide,
- c) adding meglumine,
- d) carrying out the complexing of the lanthanide with the macrocyclic chelate, in the presence of the meglumine, at a pH between 6.5 and 8.0, wherein the lanthanide is present in molar excess to meglumine and wherein meglumine is present in molar excess to the macrocyclic chelate,
- e) adjusting the pH of the solution obtained after step d) to a target pH value below 5.0 by stepwise adding an acid in increments,
- e1) after the target pH value has been reached, adding a final amount of the acid,
- f) after step e1), adjusting the pH to a value above 6.5, and
- g) diluting the solution obtained after step f) to the specified final volume,
- wherein the method is performed in a single vessel;
- and
- wherein the method is further defined as an industrial-scale method.
A method for producing an aqueous liquid preparation containing, as contrast agent for magnetic resonance, a complex of gadolinium and DOTA, the preparation containing free DOTA, the method comprising:
- a) dissolving DOTA in water,
- b) adding gadolinium,
- c) adding meglumine,
- d) carrying out the complexing of gadolinium with DOTA, in the presence of the meglumine, at a pH between 6.5 and 8.0, wherein gadolinium is present in molar excess to meglumine and wherein meglumine is present in molar excess to DOTA,
- e) adjusting the pH of the solution obtained after step d) to a target pH value below 5.0 by stepwise adding further DOTA in increments,
- e1) after the target pH value has been reached, adding a final amount of DOTA,
- f) after step e1), adjusting the pH to a value above 6.5, and
- g) diluting the solution obtained after step f) to the specified final volume,
- wherein the method is performed in a single vessel;
- and
- wherein the method is further defined as an industrial-scale method.
A method for producing an aqueous liquid preparation containing, as contrast agent for magnetic resonance, a complex of gadolinium and DOTA, the preparation containing free DOTA, the method comprising:
- a) dissolving DOTA in water,
- b) adding gadolinium,
- c) adding meglumine,
- d) carrying out the complexing of gadolinium with DOTA, in the presence of the meglumine, at a pH between 6.5 and 8.0, wherein gadolinium is present in molar excess to meglumine and wherein meglumine is present in molar excess to DOTA,
- e) adjusting the pH of the solution obtained after step d) to a target pH value below 5.0 by stepwise adding further DOTA in increments,
- e1) after the target pH value has been reached, adding a final amount of DOTA,
- f) after step e1), adjusting the pH to a value above 6.5 by adding further meglumine, and
- g) diluting the solution obtained after step f) to the specified final volume, wherein the solution contains free DOTA, wherein the free DOTA in the solution is up to 2000 ppm;
- wherein the method is performed in a single vessel;
- wherein at least both of the following in-process checks are performed when performing the method:
- endotoxin check and total bacterial count, and
- wherein the method is further defined as an industrial-scale method.
Dependencies are inferred from the claim text.