Iodixanol Purification Using n-Propanol Crystallization
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Solution Overview
Problem
Current methods for manufacturing iodixanol, a non-ionic X-ray contrast agent, face low yield and costly, time-consuming purification processes, particularly due to the reliance on preparative liquid chromatography and high energy consumption in crystallization methods.
Innovation Solution
A purification process using n-propanol as a solvent for crystallizing crude iodixanol, allowing for a single-step crystallization that reduces energy input, solvent amounts, and total processing time to under 4 days, while achieving high purity and compliance with US Pharmacopeia specifications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If preparative liquid chromatography is used for purification, then high purity iodixanol is achieved, but the process becomes expensive and time-consuming
Solution Approach 1:
The patent changes the solvent parameter from traditional water-based systems to a specific organic solvent system (mixture of n-propanol and isopropanol in a ratio of 1:4 to 1:6). This parameter change enables crystallization at lower temperatures and achieves high purity without requiring time-consuming liquid chromatography or multiple crystallization cycles
Solution Approach 2:
The patent utilizes the phase transition of iodixanol from dissolved state to crystalline state through controlled cooling of the solvent mixture. This single crystallization step efficiently separates pure iodixanol from impurities, replacing the need for preparative liquid chromatography and reducing purification time significantly
2Productivity
If high thermal energy crystallization is used (elevated pressure and temperature above boiling point), then crystallization is achieved, but the process is time-consuming and requires about 3-5 days total
Solution Approach 1:
The patent changes the temperature parameter from elevated temperatures above boiling point to a moderate temperature range (20-40°C). This parameter change, combined with the specific solvent system, enables efficient crystallization in a single step without requiring multiple crystallization cycles, reducing total processing time to under 4 days
Solution Approach 2:
The patent uses a disposable solvent system (n-propanol and isopropanol mixture) that enables single-step crystallization. The solvent mixture is designed to work efficiently at moderate temperatures and is discarded after one use, eliminating the need for energy-intensive high-temperature processes and multiple crystallization cycles
3Manufacturing precision
If multiple crystallization steps are performed to achieve desired purity, then high purity is achieved, but the process becomes time-consuming and energy-intensive
Solution Approach 1:
The patent changes the solvent composition parameter to a specific mixture of n-propanol and isopropanol in a ratio of 1:4 to 1:6. This parameter change enables a single crystallization step to achieve the desired purity level, eliminating the need for multiple crystallization cycles and significantly reducing energy consumption
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
The process significantly enhances yield, reduces energy consumption, and simplifies the purification of iodixanol, achieving high purity and compliance with specifications within a shorter timeframe, thereby improving economic and environmental efficiency.
Implementation Method 1
A purification process using n-propanol as a solvent for crystallizing crude iodixanol
Implementation Method 2
crystallizing crude iodixanol, allowing for a single-step crystallization that reduces energy input
Data Source
AI summary
A process for the manufacture of iodixanol by performing a purification process of the crude product in a solvent comprising n-propanol. The crude product may be obtained in aqueous solution from dimerisation of 5-acetamido-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-isophthalamide ("Compound A").