Francesca Cascella successfully defended her PhD thesis

Research focused on chiral molecules at the solid state and the design of crystallisation processes.

November 13, 2021

Francesca Cascella one of our researchers, successfully defended her PhD thesis on October 1, 2021. She joined the IMPRS in May 2017 working in the group "Physical and Chemical Foundations of Process Engineering" under the supervision of apl. Prof. Dr. Heike Lorenz and Prof. Andreas Seidel-Morgenstern. The title of her thesis is  "Resolution of enantiomers of chiral compounds using crystallization processes: from fundamental studies to process development".

Her research was focused on the experimental determination of fundamental properties of chiral molecules at the solid-state and the design of crystallisation processes to isolate their enantiomers. Chirality is an important concept in life science. Small chiral molecules such as amino acids and sugars are the building blocks of biomolecules of living systems and therefore, many properties related to the interaction of drugs, agrochemicals as well as natural chiral compounds with the biological environment exhibit a marked enantioselectivity. Due to the potential different pharmacokinetics, side effects, toxicology, pharmacodynamics of enantiomers of medicinal chiral molecules, chiral drugs are almost exclusively marketed and applied as single enantiomers The thesis of Francesca Cascella provides a comprehensive experimental study on the applicability of crystallization processes for the production of pure enantiomers of pharmaceutically relevant compounds.

Three chiral model compounds which find application in the pharmaceutical industry were objects of investigation. The study includes the experimental determination of the solid-liquid equilibria of the studied systems, such as binary melt phase diagrams and ternary solubility phase diagrams, along with investigations on the solid-state properties of the model compounds as well as the design and evaluation of the crystallization processes.

The results have demonstrated how the thermodynamic and kinetic properties of the substances have profound implications on the performances of the resolution runs. Together with the feasibility study of crystallization-based resolution techniques the thesis has addressed one of the decisive aspects for the process development, i.e. the performance assessment of the crystallization processes, by determining chosen key performance indicators of the resolution runs such as purity, productivity, and yield.

Overall, this thesis has provided important tools to efficiently apply resolution techniques based on the preferential crystallization principle on two substances that are relevant for the pharmaceutical industry. Advantages and limits of the single batch and the coupled crystallizer configuration have been demonstrated for the two studied systems, through evaluation of chosen key performance indicators of the processes. The applicability of the fluidized bed crystallizer in continuous operation mode has been studied for the API guaifenesin, hence paving the way to further development of this promising method for the resolution of the enantiomers of other chiral systems.

Congratulations on your successful defence and we wish you all the best!

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