Seeding has become one of the most critical steps in optimizing crystallization behavior, process efficiency, and product quality. Inconsistent filtration rates, drying times, yields, bulk density, flow properties, and particle size distributions can often be traced back to inconsistent seeding and nucleation. Many parameters must be taken into consideration when designing a seeding strategy such as seed size, seed loading (mass) and seed addition temperature. These parameters are generally optimized based on process kinetics and the desired final particle properties and must remain consistent during scale-up and technology transfer.
Monitoring the seed behavior in situ, during the crystallization itself, provides a significant advantage during the design and scale-up of the seeding strategy. The 15-30 minutes following seed addition are generally the most critical period in ensuring the effectiveness of the seed. Mapping the seed behavior inline is often critical to ensure the batch proceeds as expected, and understanding seeding parameters means less experiments are necessary to optimize a crystallization.
More recently advanced seeding techniques have been investigated as possible alternatives to the traditional approach. One such method is to create the seed bed in-process through nucleation and growth while controlling the particle size using inline particle characterization – such as with FBRM® technology. This approach can offer significant advantages for processes where safety is a primary concern.
In the white paper – Recent Advances For Seeding A Crystallization Process, Brian O’Sullivan describes a best practice approach for designing a seeding strategy and discusses recent publications on advanced seeding techniques with real time feedback control of the particle size distribution.