Iodixanol Purification Using 1-Methoxy-2-Propanol Crystallization
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Solution Overview
Problem
The existing methods for manufacturing iodixanol, a non-ionic X-ray contrast agent, face challenges such as low yield, expensive and time-consuming purification processes, particularly due to the reliance on preparative liquid chromatography and the use of corrosive reagents, as well as inefficient energy input and solvent usage in crystallization processes.
Innovation Solution
A purification process utilizing 1-metoxy-2-propanol as a solvent for crystallization of crude iodixanol, which allows for a maximum of two crystallization steps, reduces energy input, and shortens the total crystallization time to no more than four days, achieving higher purity and efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If preparative liquid chromatography is used for purification, then purity of iodixanol is improved, but cost and time consumption increase significantly
Solution Approach 1:
The invention changes the purification parameters by using a specific solvent system (1-methoxy-2-propanol/water) and controlling crystallization conditions (temperature, pH, concentration) to achieve high purity through crystallization instead of chromatography, thereby reducing time and cost while maintaining purity
Solution Approach 2:
The invention utilizes phase transition from dissolved state to crystalline state during the crystallization process. By controlling temperature and solvent composition, iodixanol transitions from solution to solid crystals, enabling separation and purification without requiring chromatographic techniques
2Manufacturing precision
If multiple crystallization steps are performed, then purity is improved, but energy input and time consumption increase
Solution Approach 1:
The invention optimizes crystallization parameters including solvent composition (1-methoxy-2-propanol/water ratio), temperature profile, and pH control to achieve high purity in a single crystallization step, eliminating the need for multiple sequential crystallizations and thereby reducing energy consumption
3Manufacturing precision
If conventional crystallization methods are used, then purification is achieved, but handling of viscous solutions becomes difficult
Solution Approach 1:
The invention changes the solvent system to 1-methoxy-2-propanol/water mixture, which maintains appropriate viscosity and solubility characteristics throughout the crystallization process, making the solution easy to handle while still achieving high purity crystallization
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This process enhances the yield and purity of iodixanol, reduces energy consumption, and simplifies the handling of viscous solutions, achieving a higher output per reactor volume while meeting US Pharmacopea specifications.
Implementation Method 1
A purification process utilizing 1-metoxy-2-propanol as a solvent for crystallization of crude iodixanol
Implementation Method 2
crystallization of crude iodixanol
Data Source
AI summary
A process for the manufacture of iodixanol by performing a purification process of the crude product in a solvent comprising 1-methoxy-2-propanol. The crude product may be obtained in aqueous solution from dimerization of 5-acetamido-N,N′-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-isophthalamide (“Compound A”).