(6ba) Understanding Nucleation and Crystal Growth of Organic Molecular Materials with Application to Pharmaceutical Manufacturing

Crystallization plays a major role in the production of commodity chemicals, fine chemicals, and pharmaceuticals. In the latter, crystallization is heavily used as a purification method and as a means to isolate Active Pharmaceutical Ingredients (APIs) with the desired structure, habit, and particle size distribution. Despite the widespread use of crystallization processes and the increased research interest within the pharmaceutical sector, the lack of fundamental understanding of nucleation and crystal growth leads to the use of tedious and hardly generalizable process design methodologies.

Pharmaceutical crystallization processes frequently encounter a large number of development challenges. Some of the challenges are system-related, like the presence of structurally similar or toxic impurities, the appearance of new polymorphs, or the inhibition of crystallization by foreign species. Other challenges are related to the industrial setting, either as process requirements or as a short availability of development time and raw materials. In a process where small variations in solution composition will impact both thermodynamics and kinetics, and where the incorporation of impurities follows a wide variety of mechanisms, it is almost mandatory to take process development shortcuts like assuming a negligible impact of solvents and impurities on crystallization kinetics, or predicting impurity incorporation based on system-specific phenomenological models.

Research Interests:

My research interests are in understanding the mechanisms of nucleation and crystal growth, with initial focus on their interplay with foreign species and solvents. This research will lead to the development of novel mechanistic models for crystallization kinetics and impurity incorporation, ultimately assisting the automation of crystallization process development through systematic methods. A better understanding of the mechanisms of nucleation and growth will also contribute to the development of novel crystallization strategies for the control of crystal quality attributes, including the use of additives to control kinetics, impurity incorporation, and polymorphism.

Teaching Interests:

Most of my teaching experience is in undergraduate courses on Unit Operations at the pilot scale (crystallization, drum filtration, ultrafiltration, heat transfer, and reverse osmosis), and graduate courses on Good Manufacturing Practice (GMP) and quality in food, pharmaceutical, and biotech industries. As a teacher, I will develop a graduate course on industrial crystallization and a graduate course on solid state analysis of pharmaceuticals. Both courses include skills that are highly sought after in pharmaceutical research and manufacturing, but rarely offered in chemical engineering departments. My teaching methods involve a fair combination of traditional lectures and active learning, as I believe that student involvement, practical applications and spaced learning facilitate the understanding and long term retention of the taught concepts. I also strive to provide an environment where students are motivated to learn and have access to sufficient resources that meet their learning needs.