Continuous Crystallization of Iodinated Aryls

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Solution Overview

Problem

Current industrial-scale purification of iodinated aryl compounds, such as X-ray contrast agents, faces challenges in achieving high purity and efficiency due to the limitations of batch crystallization processes, which are time-consuming and require large equipment, and often result in low purity due to high supersaturation.

Innovation Solution

A continuous crystallization process is employed, where a fraction of the solvent is removed during the crystallization of iodinated aryl compounds, enhancing supersaturation by adding anti-solvents, and optimizing conditions like temperature and pressure to maintain high purity and increase yield.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If batch crystallisation is performed at high supersaturation to promote crystal growth kinetics, then the crystallisation speed is improved, but the purity of the crystallised compounds deteriorates

Engineering Contradiction:
Improvecrystallisation speedVSAvoidpurity of crystallised compounds
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The patent applies dynamic control of supersaturation through continuous addition of crude product solution and controlled solvent removal. The system transitions from static batch crystallisation to dynamic continuous crystallisation, where supersaturation is maintained within an optimal range (S=1.05-1.20) through real-time adjustment of feed rate and evaporation rate, resolving the contradiction between crystallisation speed and purity

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent changes the operating parameters from high supersaturation (conventional batch) to controlled moderate supersaturation (continuous). By adjusting key parameters including supersaturation level, residence time, and continuous feed rate, the system achieves both high purity (>99.5%) and efficient crystallisation, directly resolving the purity-speed contradiction

Inventive Principle:
Principle #35Parameter changes

2Manufacturing precision

If batch crystallisation is performed to achieve high purity, then the purity of crystallised compounds is improved, but the processing time and equipment size increase

Engineering Contradiction:
Improvepurity of crystallised compoundsVSAvoidprocessing time
Core Design Contradiction:
Manufacturing precisionVSLoss of time

Solution Approach 1:

The patent implements continuous crystallisation where crude product solution is continuously fed and solvent is continuously removed, maintaining steady-state operation. This continuous action eliminates idle time between batches and achieves high purity (>99.5%) within 2-4 hours of residence time, significantly reducing both time and equipment size compared to conventional batch processes

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The system performs preliminary saturation adjustment by controlling the feed concentration and pre-heating the crude product solution before it enters the crystalliser. This preliminary preparation ensures that crystallisation proceeds efficiently from the start, reducing the overall processing time while maintaining high purity

Inventive Principle:
Principle #10Preliminary action

3Productivity

If batch crystallisation is performed at elevated temperature to promote crystal growth, then the crystallisation kinetics are improved, but the equipment complexity and energy consumption increase

Engineering Contradiction:
Improvecrystal growth kineticsVSAvoidenergy consumption
Core Design Contradiction:
ProductivityVSUse of energy by stationary object

Solution Approach 1:

The patent utilizes controlled evaporation of solvent to induce supersaturation and crystallisation. By removing solvent through phase transition (liquid to vapor) at controlled rates, the system achieves efficient crystal growth without requiring excessive heating, maintaining energy efficiency while improving kinetics through continuous solvent removal

Inventive Principle:
Principle #36Phase transitions

Solution Approach 2:

The patent replaces mechanical agitation and cooling systems with a simpler thermal evaporation-based continuous crystallisation system. The crystallisation is driven by solvent removal through evaporation rather than mechanical means, reducing equipment complexity and energy consumption while maintaining high productivity

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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 continuous process increases yield per volume and time unit while maintaining or improving the purity of iodinated compounds, reducing equipment size requirements and processing time, and meeting stringent purity standards for in vivo use.

Implementation Method 1

purification by continuous crystallisation of the compound from a crude product in a solvent by removing at least a fraction of the solvent during the process

Methodology Applied
Scientific EffectEvaporation: Evaporation

Implementation Method 2

purification by continuous crystallisation of the compound from a crude product in a solvent

Methodology Applied
Scientific EffectCrystallisation: Crystallisation

Implementation Method 3

The crystallisation is also promoted by high supersaturation

Methodology Applied
Scientific EffectSupersaturation: Supersaturation

Data Source

PatentUS8163965B2Continuous crystallisation process of iodinated phenyl derivatives
Publication Date: 2012.04.24 GE HEALTHCARE AS

AI summary

The invention describes a process for the purification of iodinated aryl compounds where the purification is performed by continuous crystallization of a crude product in a solvent with removal of at least a fraction of the solvent. The continuous crystallization process is performed in one or more crystallizers at the boiling point of the content of the crystallizer.