Production-scale particle design of a pharmaceutical intermediate

Product requirements within the pharmaceutical and life sciences sector change rapidly due to new drug developments and applications linked to new formulations. This paper presents recent developments in designing an optimal crystallization process incorporating, at the design stage, customer demands regarding the physical properties of the crystalline product, notably particle size and particle size distribution. Simple laboratory-scale batch crystallization experiments were performed to extract the relevant kinetic parameters of nucleation, growth, and aggregation and to identify further mechanisms such as disaggregation and attrition. Aggregation, considering also nucleation and growth, was simulated via population balance modeling whereas disaggregation was considered by quantitative determination of the interparticle forces. Using this new design route, a production-scale crystallization process comprising a continuously operated air-jet crystallizer with an integrated clarification zone was successfully commissioned.