Crystallization plays a key role in the development and production of APIs. It directly influences the purity, particle size distribution, and processability of the final product. In addition to producing chemically pure APIs, the crystallization process also determines the crystal form and particle size distribution, which in turn affects the dissolution rate.
From Purity to Performance: Why Crystallization Matters
The quality of crystallization process affects the homogeneity and consistency of the API. Uniform crystal form and PSD ensure that the drug behaves predictably during formulation. Because crystal structures are selective toward specific molecular arrangements, incorporating crystallization into the manufacturing process offers a highly effective route to achieving chemical purity.
Modern Approaches to Crystallization
Though crystallization is a long-established technique, recent advances have improved how it’s studied and controlled. At Fermion, development begins with a deep understanding of solubility and solvent behavior. Tools like solubility testing, metastable zone mapping, and supersaturation control guide process design.
Process Analytical Technology (PAT) tools have transformed crystallization development. These tools allow real-time monitoring of quality parameters such as crystal form, particle size, and supersaturation. This enhances process understanding, repeatability and control, which are especially important when scaling up from lab to production.
From Laboratory to Production
Crystallization methods are developed with scalability in mind. Parameters such as mixing, seeding, cooling profiles, and solvent ratios are optimized to ensure consistent performance at production scale. The aim is to achieve high yield, good filterability, minimal waste generation, and consistent product quality throughout scale-up, while supporting cost-efficient manufacturing.
A critical part of this process is selecting the right solvent or solvent combination. Solvents are chosen not only for their ability to dissolve the API and influence crystal form, but also for their effectiveness in purification. In addition to technical performance, environmental impact, worker safety, and energy efficiency are important considerations. The objective is to identify a solvent system that balances product quality with sustainable and safe manufacturing practices.
Looking Ahead: The Future of Crystallization
“Crystallization is a central part of post-reaction downstream processing, significantly affecting the final product’s properties.”
— Hannu Alatalo, Senior Scientist
Crystallization will remain a cornerstone of API manufacturing. The use of PAT tools is expected to expand, particularly in continuous processing and advanced development. As standards evolve, crystallization will continue to enable safe, effective, and high-quality pharmaceuticals.
Crystallization is not just a technical step. It is a strategic capability that underpins the quality, safety, and performance of pharmaceutical products. At Fermion, it is treated as a core competence, essential to delivering reliable and effective medicines.