Applications > Crystallization

Improve Your Crystallization Process with Advanced Particle Analysis

Various crystalline products including pharmaceutical API, food products and chemicals

Crystallization is a critical purification and separation process used in industries such as pharmaceuticals, chemicals, and food production to achieve high-purity products and control particle properties. Precise monitoring of the crystallization process is essential for ensuring product quality and optimizing process efficiency. Advanced image-based particle analysis provides detailed insights into key crystallization parameters, enabling better process control and optimization.

Challenges in Crystallization

Crystallization pathways
Figure 1: Particle formation during crystallization can follow different morphological pathways dependent on the process parameters.

Crystallization is a complex process influenced by multiple factors, including temperature, supersaturation levels, mixing conditions, and impurities. To achieve high-quality and consistent crystals, precise control over the three key crystallization phenomena — nucleation, growth, and agglomeration — is essential. Even small variations in process conditions can significantly impact process kinetics, affecting downstream efficiency, overall yield, and final product quality.

Without proper monitoring and optimization, crystallization processes can lead to inconsistent purification and suboptimal product properties. Some of the most common operational challenges include:

  1. Inconsistent crystal size distribution: Leads to varying downstream performance (filtration and drying efficiency) and product variability (dissolution rates and product performance).
  2. Variations of crystal shape, morphology and polymorphism: Affect product flowability, compaction, and bioavailability in pharmaceutical applications.
  3. Unwanted agglomeration: Uncontrolled agglomeration leads to broader particle distributions, affecting product purity, yield, and causes batch-to-batch variations.
  4. Suboptimal throughput: Conservative operation at low supersaturation levels to prevent secondary nucleation can lead to unnecessarily slow crystal growth rates, reducing overall process efficiency and extending batch times.

Solving the Challenges with 3D Scanning and Advanced Image Analysis

Figure 2: Example of a crystal width size distribution for a crystal slurry sample
Figure 3: Particle mosaic from the ParticleTech Analyzer Software

Effective monitoring of the crystallization process is key to overcoming common operational challenges. It enhances control over crystallization conditions and improves process robustness, making operations less sensitive to disturbances. This leads to higher product consistency, improved yield, and reduced waste.

Our advanced particle analysis technology, powered by 3D scanning and state-of-the-art image analysis algorithms, provides an instant, detailed overview of the crystallization process. In a single analysis, you gain critical insights into:

  1. Crystal size distribution (CSD): Ensures uniform crystal growth and optimized downstream processing
  2. Crystal shape and morphology analysis: Detects variations that may impact product performance and stability
  3. Agglomerate detection: Identifies unwanted clustering that can affect filtration and purity
  4. Secondary nucleation detection: Monitors excessive nucleation that may lead to reduced crystal sizes and .
  5. Seed slurry analysis: Provides quantification of seed crystal concentration (crystal count per volume of slurry) alongside seed crystal size distribution, ensuring better nucleation and growth kinetics control.

The key advantages of this are:

  • Real-time process optimization: Enables immediate adjustments for tighter process control and improved product consistency.
  • Better control of seeded crystallizations: Accurate seed slurry analysis allows for optimized seeding strategies, leading to more reproducible batch outcomes.
  • No calibration: Eliminates downtime due to product-specific calibration steps.
  • Hands cleaning: No manual cleaning is needed, allowing for uninterrupted analysis.
  • Rapid results: Get a full analysis in under 2 minutes, significantly reducing reaction time.

Our analysis technology provides detailed characterization at the individual crystal level, measuring the physical properties of each crystal to generate precise population metrics such as size and shape distributions. This enables advanced classification of crystals, allowing for the detection of agglomerates and conglomerates, as shown in Figure 4. By leveraging this data, operators can proactively adjust process parameters to enhance crystallization efficiency and product purity.

Figure 4: Advanced classification of single and agglomerated crystals, to optimize processing conditions to reduce agglomeration