Crystallisation & Precipitation

Crystallisation and precipitation processes are commonly used in the pharmaceuticals, chemicals, and in the food and food supplements producing industries to separate, purify and recover solid products. Such processes are generally difficult to develop and control, in particular when stringent product specifications are set by the customer for end-use. The product characteristics specified vary from particle size distribution, shape and purity of the crystals, to a particular crystalline form with consistent and well-characterized physical properties such as solubility and dissolution rate. The course uniquely covers the principal factors that influence effective crystallisation, the selection of an appropriate crystallisation method and its mode of operation, and also the control and monitoring of solid state characteristics. This latter aspect includes the identification and classification of polymorphs and alternative solid forms that may be developed to tailor the physical properties.

Target group

The course is designed for professional engineers and scientists in industry and academia who need to understand the principles that underlie crystallisation and precipitation, the ways in which suitable processes can be selected, and how to characterize the solid form and properties of the solids obtained.

Programme

The course will give an overview of the principles by which suitable crystallisation and precipitation processes can be identified and developed, and also the ways of characterizing solid products both in terms of particle size related properties and solid state characteristics. You will gain a deeper understanding of the relationship between operating conditions and product characteristics.  

First two days at TU Delft, Delft:

• Physical characterisation of products: particle size distribution, shape and size of crystals, purity and relation to product and process features. 
• Methods of crystallisation: melt, evaporative, cooling, anti-solvent, mechano crystallisation and precipitation; supersaturation, solubility and solution speciation.
• Kinetics of crystallisation: nucleation, growth and agglomeration.
• Process modeling: population balance equation, crystallizer configuration and control in evaporative and cooling crystallisation.
• Batch crystallisation: cooling curves, preparation and use of seeds.
• Precipitation and anti-solvent crystallisation: mixing, nozzle design.
• Process measuring techniques: particle size distribution, concentration, solubility, supersaturation.
• Polymorphism: stable and metastable forms, monotropy and enantiotropy, preparation and screening of polymorphs.
• Alternative solid forms: salts and co-crystals, methods of preparation.
• Supercritical crystallisation: Ress, Gas, nano-particles, intimate mixtures.
• Crystallisation of chiral compounds; enantiomer resolution. 

Third day at Avantium Technologies, Amsterdam:

• Introduction - Crystallisation, solid form and experimental design.
• Interactive group sessions (max. 10 in each group):   Practical on solubility measurement; Solubility models; Design of solid form screens;  Crystallisation development; nucleation and metastable zone width. Practical on crystallisation in Crystal16™;  Laboratory tour. Practical on evaporative and cooling crystallisation and analysis of outcomes.
• Characterisation of solid forms: X-ray Diffraction, thermal analysis, IR/Raman. Example (tiotropium fumarate).
• Case Study Exercise: solid form assignment from analytical data.

The course lecturers and Avantium personnel will be available during the day for discussions and free consultancies.

Costs

Programme fee: € 2.250
Costs of accommodation: about € 240 (excluding Dutch VAT) Staying overnight: € 120 p.p.p.n. (excluding Dutch VAT)
The programme fee is exempt from Dutch VAT. Prices cover all costs involved in the programme, i.e. compulsory literature. The costs of accommodation and lodging will be charged separately.

If you want, we can reserve a hotel room for you for the nights between the course days and the night before the course starts. After application, you will be asked for further details.