Production of pharmaceutical products: development, optimisation, and scaling-up of crystallisation processes

The Crysforma team develops regular methods for clients according to their solid-state property requirements

Crysforma, the unit specialised in solid-state development at the Institute of Chemical Research of Catalonia (ICIQ-CERCA), creates and refines processes to make crystals that meet specific needs in their properties, with a primary focus on creating key components for pharmaceutical drugs.

The development of a crystallisation process involves a series of steps from a small scale of millilitre range, up to a scale-up in a 6-litre reactor:

• Design of the crystallisation method: the crystallisation method is developed at a low scale, by screening different solvents and crystallisation methodologies.
• Optimisation of the method: this step focuses on finding the best conditions for making crystals in a way that is reliable and consistent, especially to avoid any setbacks when applying the process on a large scale in industries. They use statistical data from a ‘design of experiments (DoE)’ and analyse it with software. This helps them to figure out the key factors that influence the process and the best values for these factors. The goal is to create a reliable method that gives the product the properties they are aiming for.
• Scale-up of the process: the optimised method can be scaled up in a fully controlled reactor, simulating the large industrial production conditions. In this process, the crystallisation parameters can also be fine-tuned to achieve the best possible result.

The experienced scientists of Crysforma-ICIQ specialised in crystallisation screenings and characterisation of the solid state offer high-quality studies to improve and meet the different property requirements, such as those related to purity profile, polymorphism, particle size distribution, particle morphology and performance.

To achieve these goals, they have access to specific equipment, including screening crystallisation systems from 1 mL to 100 mL, equipment for solubility and metastable zone width determination, and automated scale-up reactors from 0.5 L to 6 L.

The evaluation of the suitability of the process is carried out using state-of-the-art analytical techniques available at ICIQ, with a focus on X-Ray diffraction (PXRD), thermal analysis (DSC and TGA), particle size distribution (PSD), microscopy and chromatography.