Crystallization Cooling Control for Metastable Zone Stability

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Solution Overview

Problem

Current crystallization processes in the pharmaceutical and chemical industries face challenges in accurately controlling cooling rates and maintaining metastable zones, leading to inconsistencies in particle size, morphology, and regulatory compliance due to unaccounted process disturbances and inadequate temperature control.

Innovation Solution

A method and system that capture and predict process parameters using sensing units, including temperature sensors and flow meters, to compute and control the cooling rate and utility flow, employing a smart positioner and control system to maintain precise cooling control within the metastable zone, thereby ensuring desired crystal morphology and yield.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If manual or traditional PID control is used for crystallization, then operation simplicity is maintained, but temperature control precision deteriorates leading to inconsistent particle size and morphology

Engineering Contradiction:
Improveparticle size controlVSAvoidcontrol system complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The system implements a closed-loop feedback control mechanism where temperature sensors continuously monitor the crystallization mass temperature, and the control system adjusts utility flow based on the difference between actual and desired temperature profiles. This feedback loop maintains precise temperature control within the metastable zone, ensuring consistent particle size and morphology without requiring overly complex manual intervention.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The system pre-calculates and stores desired temperature profiles and utility flow rates before the crystallization process begins. These predetermined profiles are based on the specific crystallization requirements and metastable zone characteristics. During operation, the system follows these pre-planned trajectories, allowing precise particle size control while simplifying real-time decision-making.

Inventive Principle:
Principle #10Preliminary action

2Productivity

If cooling rate is increased to reduce batch cycle time, then productivity improves, but temperature control stability deteriorates causing overshoot and non-compliance with regulatory standards

Engineering Contradiction:
Improvebatch cycle timeVSAvoidtemperature control stability
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The control system dynamically adjusts the cooling rate based on real-time temperature measurements and process stage. During different phases of crystallization (nucleation, growth, maturation), the system optimizes the cooling rate to maintain stability while progressing through the batch cycle. This dynamic adaptation allows faster overall cycle times without sacrificing temperature control stability or regulatory compliance.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The system changes multiple parameters simultaneously including utility flow rate, cooling jacket temperature, and agitation speed to maintain optimal cooling rates. By coordinating these parameter changes, the system achieves faster batch cycles while preventing temperature overshoot and maintaining stability throughout the crystallization process.

Inventive Principle:
Principle #35Parameter changes

3Adaptability or versatility

If multiple cooling utilities are used to cater to multiple reactors, then system versatility improves, but process control precision deteriorates due to inadequate cooling system capacity and unaccounted disturbances

Engineering Contradiction:
Improveutility management flexibilityVSAvoidcooling rate control
Core Design Contradiction:
Adaptability or versatilityVSManufacturing precision

Solution Approach 1:

The system independently controls and monitors each cooling utility and reactor combination, allowing tailored cooling profiles for different reactors based on their specific requirements. Each reactor-utility pairing has dedicated control parameters and disturbance compensation, ensuring precise cooling rate control even when multiple utilities are simultaneously operating with different capacities and characteristics.

Inventive Principle:
Principle #3Local quality

4Reliability

If cooling rate is reduced to maintain stability, then temperature control reliability improves, but particle size distribution deteriorates leading to filter screen passage and yield loss

Engineering Contradiction:
Improvetemperature control stabilityVSAvoidcrystal yield
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The system employs periodic or pulsed cooling action during specific stages of crystallization to maintain supersaturation levels that promote crystal growth while preventing excessive nucleation. By applying cooling in controlled intervals rather than continuously, the system achieves both temperature stability and optimal particle size distribution, maximizing crystal yield that can be efficiently filtered and recovered.

Inventive Principle:
Principle #19Periodic action

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 approach enables precise control of nucleation and crystal growth, improving particle size distribution, reducing energy consumption, and ensuring compliance with regulatory standards by accurately managing cooling rates and utility flow, thus enhancing the consistency and efficiency of the crystallization process.

Implementation Method 1

The one or more sensing unit comprises one or more temperature sensors external to the operating reactor unit for measuring utility jacket inlet temperature and jacket outlet temperature, one or more temperature sensor deployed internal to the operating reactor unit for measuring crystallization mass temperature

Methodology Applied
Scientific EffectTemperature measurement:

Implementation Method 2

one or more flow meters for measuring utility flow rate

Methodology Applied
Scientific EffectFlow measurement:

Implementation Method 3

The process of cooling involves use of different utilities for cooling purpose. These utilities are circulated in a jacket / coils of reactor

Methodology Applied
Scientific EffectHeat removal:

Implementation Method 4

These utilities are circulated in a jacket / coils of reactor

Methodology Applied
Scientific EffectHeat transfer: Heat Exchanger

Implementation Method 5

Cooling type crystallization is a thermal separation and purification process which yields a solid product from a solution

Methodology Applied
Scientific EffectCrystallization: Crystallisation

Implementation Method 6

Cooling type crystallization is a thermal separation and purification process

Methodology Applied
Scientific EffectThermal separation:

Implementation Method 7

To establish this non equilibrium conditions, evaporation of solvent or temperature reduction (cooling) methods are more frequently employed in the process control industry

Methodology Applied
Scientific EffectEvaporation: Evaporation

Data Source

PatentEP4045980B1System and method for managing crystallization process in process control plant
Publication Date: 2023.12.27 SIEMENS AG
  • EP4045980B1 patent drawingFigure 1
  • EP4045980B1 patent drawingFigure 2
  • EP4045980B1 patent drawingFigure 3

AI summary

The present invention provides a method for managing crystallization process in a process control plant. The method comprises capturing process parameters of an operating reactor unit (102) in a process control plant (100). The method comprises predicting desired process parameters based on first set of parameters and the captured process parameters. The first set of parameters comprises information related to process dynamics and process disturbances associated with the operating reactor unit (102). Furthermore, the method comprises controlling process control loop associated with the operating reactor unit (102) based on the desired process parameters and the first set of parameters.