Within the framework of this project we are working on the establishment of a continuous crystallizer for active pharmaceutical ingredients (APIs). More than 90% of all APIs are processed in the crystalline state and therefore the development of a high-throughput facility including tailoring of the compound’s particle properties is pursued. Important quality attributes of the final products used in the pharmaceutical industry include the dissolution and disintegration rate, the stability and the flowability as well as the compactibility and tabletability. All of these are closely dependent on crystal properties such as crystal shape, size and size distribution. As a model system, the crystallization of acetylsalicylic acid (ASA) from an ASA-ethanol solution was chosen. By continuously seeding the feed solution and installing a slug flow for a narrow residence time distribution, we already succeeded in influencing the product properties according to our requests. Because of the large surface-to-volume ratio of the system heat of crystallization can be removed immediately, thereby avoiding uncontrolled growth conditions caused by temperature oscillations.
In future work we will focus on modelling of the crystallization process by means of population balance equations (PBE) coupled with mass and energy balances. These simulations will be used to optimize the overall process, especially with respect to cooling trajectories. Moreover we will evaluate the system for the capability of controlling polymorphism and solvate formation, and by implementing a feed forward and a feedback control an even tighter regulation of the CSD should be achieved.
Sponsored By
Austrian Science Foundation (FWF)
