Crystallization is a key unit operation in the pharmaceutical industry. Control of crystallization processes can be challenging when undesirable phenomena such as particle attrition and breakage occur. This thesis describes the controlled crystallization of pharmaceuticals and amino acids for more efficient manufacturing processes and better efficacy of products. Crystallization equipment is de...

Crystallization processes in the pharmaceutical industry are usually designed to obtain crystals with controlled size, shape, purity, and polymorphic form. Knowledge of the process conditions required to fabricate crystals with controlled characteristics is critical during process development. In this work, continuous crystallization of Ketoconazole, Flufenamic Acid, and L-Glutamic Acid in a no...

The population balance equation is used to describe the dynamics of a continuous crystallizer. A simple condition to guarantee the stability of a mixed suspended mixed product removal crystallizer is derived based on the population balance. A novel discretization scheme solves the population balance and the resulting discretized population balance is shown to be equivalent to the original popul...

This work investigates the effects of different seeding strategies and residence time characteristics on the dynamics of a Mixed Suspension Mixed Product Removal (MSMPR) crystallizer equipped with a fines dissolution unit and applied to continuous preferential enantioselective crystallization. The fines dissolution is included as recycle streams around the MSMPR crystallizer. Moreover, primary ...

During crystallization the control and effective distribution of heat transfer from the solution to the heat exchanger (HE) plays an important role. Inhomogeneity in temperature on the HEsurface limits the production capacity and increases the tendency of an isolating scale layer formation. To avoid scaling, scraper blades on the HE are commonly used. In a typical axi-symmetric geometry the sca...

In this paper, we propose a concept of knowledge management “Knowledge Liquidization and Crystallization”, and a system “Knowledge Nebula Crystallizer” to support the process. “Exhibition designing” was chosen as an application of our methodology to a real work place in cooperation with a Japanese advertising company, as it is an example of the tasks that highly depend on implicit knowledge of ...

Computational fluid dynamics (CFD), micromixing modeling, and the population balance equation (PBE) are coupled to simulate the crystal size distribution in a confined impinging jet crystallizer. For the antisolvent crystallization of lovastatin in confined impinging jets, the simulation results show varying degrees of inhomogeneity in the supersaturation and the nucleation and growth rates in ...

A novel continuous heterogeneous crystallization process is developed in which the active pharmaceutical ingredient (API) is crystallized directly on the surface of an excipient within the crystallizer. The product is subsequently dried and formed into tablets without the need for complex downstream processing steps, such as milling, sieving, granulation, and blending. The aim is to eliminate m...

The separation of enantiomers is of great importance due to their possible differences in therapeutic properties. Preferential crystallization in various configurations of coupled batch crystallizers is used as an attractive means to separate the conglomerate-forming enantiomers from racemic mixtures. However, the productivity of such batch processes can be limited by the nucleation of the coun...