Overcoming the complexities of agrochemical crystallization: Insights from industry experts
In agrochemical manufacturing, isolating the crystal form that provides the desired activity for the product’s purpose is essential to achieving high product quality, yield, and cost efficiency. However, understanding the mechanisms of crystallization and controlling the outcome is challenging, especially during scale-up.
In our past webinar, we gathered industry experts from Malvern Panalytical, Syngenta, and Siemens to discuss critical challenges and share practical solutions. They highlighted the use of advanced characterization and modeling tools to overcome these challenges.
Dr. Alan Collier (Syngenta), Dr. Niall Mitchell (Siemens), and Dr. Jenny Burt (Malvern Panalytical) each shared expert insights on using particle characterization and crystallization modeling to address common pain points in the process. By integrating experimental data with sophisticated models, they offered methods to better predict and control crystallization outcomes.
Key takeaways
- Wrong enantiomers can reduce yields but can also be removed or reduced
Some enantiomers have reduced or even adverse biological effects and therefore need to be removed or reduced from the product. However, they have similar properties so isolating them can be difficult. By reacting with other enantiomers to form diastereomers with different properties, they can be selectively crystallized and removed from the mother liquor. Thereby improving yield.
- Measurement challenges in crystallization
Needles are bad! Particles shaped like needles form dense agglomerated mats that clog up filters and prolong the production process. Image analysis can be used to quantify needle formation. However, high solid loadings and complex binary mixtures make in-situ analysis challenging. Hence, ex-situ techniques are often preferred.
- Modeling and optimization
Using the gPROMS Formulated Products software, manufacturers can create predictive models that consider particle morphology, enabling efficient design and scale-up of crystallization processes. This approach helps in exploring and optimizing conditions to achieve the desired particle characteristics and enhance production efficiency.
Over the past couple of years, we’ve been collaborating with experts in process engineering, modeling, and material characterization to understand crystallization control mechanisms, and we have an excellent example to share.
Robert Taylor, Marketing Segment Manager, Malvern Panalytical
The complexity of measuring agrochemical crystallization
In industrial crystallization, measuring particle characteristics accurately is vital for ensuring a consistent end product. However, measurement challenges are significant because the systems often have high solids loading, complex multiphase compositions, and non-homogeneous conditions, which create unique difficulties in imaging and measuring particles.
Malvern Panalytical’s Morphologi range for advanced static image analysis and the Hydro Insight dynamic image analysis systems are designed to tackle these issues:
- Static image analysis on the Morphologi allows for detailed measurements of particles from sub-micron levels to over a millimeter in size. This method is particularly beneficial when measuring particles with high aspect ratios – like needle-shaped crystals – commonly found in agrochemical processes.
- Dynamic image analysis, enabled by the Hydro Insight accessory, provides a more dynamic characterization of particles within a flowing medium. This setup collects both laser diffraction and image data simultaneously, allowing for particle size distribution information alongside shape analysis.
The Morphologi system is also capable of performing morphologically directed Raman spectroscopy (MDRS); a combination of image analysis and chemical identification that helps differentiate polymorphs in mixed crystal populations. By identifying the different components, scientists can learn which polymorph is forming which shape to better understand the mechanisms of crystal growth.
The challenge of enantiomers and impurities
Managing enantiomers and impurities in agrochemical crystallization is particularly challenging. Enantiomers, or mirror-image molecules, can impact a product’s effectiveness and safety, as each mirror image may have different biological activities. This characteristic poses difficulties in achieving purity, as separating enantiomers at an industrial scale is both technically complex and resource intensive.
Impurities pose additional challenges. In high solids loading environments, impurities may form solid solutions with the intended crystal or even crystallize separately, affecting the crystal morphology and potentially the efficacy of the final product. Impurities can significantly influence the crystal’s formation and stability, sometimes requiring further filtration or purification steps to isolate the desired form.
These challenges underscore the importance of advanced characterization and modeling techniques that enable the identification and differentiation of crystal types, as these tools allow for more targeted and effective separation processes.
Enantiomers are mirror-image molecules that can have significant differences in biological activity. While the chemical formula remains the same, the mirror-image structures cannot be superimposed. This often means both forms will have the same physical properties, making separation difficult.
Alan Collier, Syngenta
Optimizing through modeling
Effective crystallization in agrochemicals relies on accurate measurement and predictive modeling. Siemens’ gPROMS FormulatedProducts software enables researchers to simulate and optimize crystallization processes, creating predictive models that allow researchers to simulate changes in particle shape, size, and distribution.
This approach is vital for scaling up from lab-scale experiments to large industrial crystallizers, allowing researchers to validate the model with small-batch data before applying it on a larger scale to explore the process design space.
Using advanced characterization techniques alongside modeling software like gPROMS, manufacturers can better understand and control the crystallization process, improving product quality and efficiency. This holistic approach offers a clear path to addressing the complex demands of agrochemical manufacturing.
You can watch the webinar recording here – and if you’d like to learn more, why not book a demo of the Morphologi range?