Progressive Emulsion Crystallization for Organic Purification

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Solution Overview

Problem

Current emulsion crystallization methods face challenges in achieving high yields, efficient separation of related impurities, and large-scale production of pure organic molecules, especially when dealing with crude materials containing impurities with similar structures, due to issues like low emulsion stability, long crystallization times, and high surfactant content.

Innovation Solution

The Progressive Emulsion Crystallization (PEC) process, which involves forming emulsions with a Gibbs free energy of droplet formation ΔG > 0, using a homogenization system to control suspension, and optimizing cooling ramps for crystallization, allows for efficient purification of organic molecules by seeding at higher temperatures and controlling the crystallization temperature to produce large particles with good filtration properties.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If emulsion crystallization is used to purify organic molecules, then separation of impurities is achieved, but crystallization time becomes excessively long

Engineering Contradiction:
Improvepurity of productVSAvoidcrystallization time
Core Design Contradiction:
Manufacturing precisionVSLoss of time

Solution Approach 1:

The patent applies preliminary action by pre-forming stable emulsion droplets with controlled size distribution before the crystallization process. The emulsion is prepared with optimal surfactant concentration and droplet size (0.1-10 μm) in advance, which provides a ready-made template for crystal formation. This preliminary preparation eliminates the need for slow in-situ emulsion formation during crystallization, thereby reducing overall process time while maintaining high purity separation.

Inventive Principle:
Principle #10Preliminary action

2Stability of the object's composition

If surfactant is added to form stable emulsion, then emulsion stability is improved, but amount of surfactant required increases

Engineering Contradiction:
Improveemulsion stabilityVSAvoidamount of surfactant
Core Design Contradiction:
Stability of the object's compositionVSQuantity of substance

Solution Approach 1:

The patent applies parameter changes by optimizing the surfactant concentration to a specific range (0.1-5% w/v) and controlling droplet size (0.1-10 μm) to achieve maximum emulsion stability with minimal surfactant. The invention identifies critical parameters such as surfactant type (ionic vs. nonionic), concentration, and droplet size distribution, and adjusts these parameters to find the optimal balance between stability and surfactant usage. This allows achieving stable emulsion with lower surfactant amounts compared to conventional methods.

Inventive Principle:
Principle #35Parameter changes

3Manufacturing precision

If emulsion is cooled to low temperature for crystallization, then purity of crystals is improved, but filtration difficulty increases due to small particle size

Engineering Contradiction:
Improvepurity of crystalsVSAvoidfiltration ease
Core Design Contradiction:
Manufacturing precisionVSEase of manufacture

Solution Approach 1:

The patent applies preliminary action by pre-establishing a stable emulsion matrix with controlled droplet size before crystallization. The emulsion droplets act as pre-formed templates that guide crystal growth, ensuring that crystals form within or on the surface of droplets of optimal size. This preliminary structuring prevents the formation of excessively fine crystals that would be difficult to filter, while still allowing high purity separation through the emulsion matrix.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent applies flexible shells and thin films by utilizing the emulsion droplet interface (stabilized by surfactant) as a flexible template for crystal growth. The surfactant film at the droplet interface provides a controlled environment that guides crystal nucleation and growth, allowing crystals to form with optimal size and morphology. This interface acts as a flexible template that can accommodate different crystal sizes while maintaining the benefits of emulsion crystallization.

Inventive Principle:
Principle #30Flexible shells and thin films

4Productivity

If seeding is performed at low temperature to promote crystallization, then crystallization speed is improved, but risk of impurity crystallization increases

Engineering Contradiction:
Improvecrystallization speedVSAvoidselectivity of crystallization
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The patent applies local quality by creating different local environments within the emulsion system. The emulsion droplets provide localized zones with controlled composition, size, and surface properties that favor selective crystallization of the desired compound. By controlling droplet size distribution and surfactant type, the invention creates local conditions that promote preferential nucleation and growth of target crystals over impurity crystals, even at temperatures where both might otherwise crystallize.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent applies intermediary (mediator) by using the emulsion droplet interface and surfactant molecules as intermediaries that mediate between the bulk solution and the crystallizing molecules. The surfactant at the droplet interface acts as a mediator that selectively interacts with the target compound, promoting its crystallization while excluding impurities. This intermediary layer provides selectivity that prevents impurity crystallization even at lower temperatures where seeding is performed.

Inventive Principle:
Principle #24Intermediary (Mediator)

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

PEC achieves high yields and effective separation of impurities, suitable for large-scale industrial production with minimal surfactant use, producing highly pure products with improved filtration properties.

Implementation Method 1

emulsions with a Gibbs free energy of droplet formation ΔG > 0

Methodology Applied
Scientific EffectGibbs free energy:

Implementation Method 2

dissolving the aggregate mixture at higher temperatures, cooling the emulsion to lower temperature and gaining a high level of super saturation

Methodology Applied
Scientific EffectSuper saturation: Supersaturation

Implementation Method 3

seeding is used to promote crystallization

Methodology Applied
Scientific EffectCrystallization: Crystallisation

Implementation Method 4

seeding with crystals of the pure substance is carried out at a higher temperature than the temperature at which the crystallization is completed

Methodology Applied
Scientific EffectNucleation: Nucleation

Data Source

PatentEP2413911B1Progressive emulsion crystallization
Publication Date: 2014.02.19 KRKA D D NOVO MESTO
  • EP2413911B1 patent drawingFigure 1
  • EP2413911B1 patent drawingFigure 2
  • EP2413911B1 patent drawingFigure 3

AI summary

The invention described herein is in the field of separation processes, more particularly, in the field of selective crystallization methods for purification of organic substances.