Crystallization Scale-up Strategy Development
During this webinar, two case studies are presented to illustrate how to understand and manage the interactions between hydrodynamics and the kinetics of a crystallization in order to deliver appropriate scale-up solutions.
The successful design of a crystallization process intended for operation at scale is dependent on having a good understanding of the implications that mixing has on the final crystal product quality, including:
- Particle Size Distribution
- Polymorphic Form
In a batch cooling crystallization, these mixing effects have influence over supersaturation, particle attrition and agglomeration which need to be effectively controlled; particularly as the process is scaled-up from a small scale lab environment to a manufacturing facility. In the case of a reactive or anti-solvent crystallization, these mixing effects become even more crucial as they involve the blending of different solvents, reagents etc and achieving homogeneity is not straightforward. As a result, strategies need to be developed and deployed that ensures the successful scale-up of a crystallization process that produces drug product of consistent quality. The use of Process Analytical Technology (PAT) and modelling strategies are powerful technologies to enable the development of fundamental process understanding at the laboratory scale in order to deliver a right-first-time crystallization scale-up.
This on-demand webinar includes:
- Crystallization Scale-up Overview
- Mixing Implications and Criteria for Crystallization Processes
- Classical Engineering Calculations Approach
- Case Study 1: Classical cooling crystallization whereby a process is delivering variable PSD at both lab and plant scale reactors. Requirement to identify the most suitable scale-up criteria for improved process robustness.
- Case Study 2: pH-adjusted crystallization whereby HCI.IPA was added to a solution of freebase in IPA over a three stage addition profile. Variable output PSD. Evidence of undesired form precipitating prior to form conversion over a short time scale.
- Concluding Remarks
Damian Duffy is a team lead in small molecule process development at APC Ltd in Dublin, Ireland where he has been working on crystallization/organic process research and development, continuous crystallization and process modelling. Having obtained a degree in Chemical Engineering from University College Dublin (UCD), he went on to earn a PhD in Control of Crystallization Processes under Professor Brian Glennon at UCD. He has publications on crystallization control and significant interest in crystallization process scale-up using Process Analytical Technology (PAT) and modelling.