The CORE Network has made excellent progress to overcome the identified technological challenges in Enabling, Hybrid and Continuous Resolution.
Enabling Resolution.
Crystallization-enabled Resolution can be highly effective and efficient due to the near-perfect selectivity of the solid phase, even in chiral systems. However, there was a lack of underlying fundamental knowledge on solid state, crystallization behaviour and in situ process analysis. The CORE Network ESRs have achieved to 1. Apply in situ Process Analytical Tools to monitor resolution processes, 2. Determine and explain phase diagram and crystallization behaviour in complex multicomponent chiral systems, 3. Uncover scientific relations for forming conglomerates and racemic compounds.
Hybrid Resolution.
The discovery of the far-reaching deracemization process of Viedma Ripening has markedly increased the scientific interest in crystal chirality. Deracemization is a Hybrid Resolution which combines reaction and crystallization steps to transform the unwanted to the preferred enantiomer and in principle reach 100% rather than 50% yield. It is a technological challenge to apply Hybrid Resolution and to fully exploit its innovative opportunity potential. The CORE Network ESRs have explored the synergistic combination of reaction and crystallization towards increased yields and productivities while the library of racemization and non-selective reversible reactions is extended. For instance, a deracemization method for the network model compound praziquantel, which is an essential medicine for schistosomiasis (bilharzia or snail fever) in developing countries, was developed.
Continuous Resolution.
We are on the verge of a paradigm shift from batch to continuous manufacturing in pharmaceutical, specialty chemicals and other industries. This shift is necessary to cope with increased molecular size & complexity, quality & purity specifications and sustainability demands of future manufacturing processes in these industries. Industry now recognizes that it is faced with technological challenges enabling the translation of the conventionally performed batch-wise crystallization processes to continuous crystallization processes. The CORE Network ESRs have created various continuous and semi-continuous resolution process configurations while short-cut and elaborate continuous process models were constructed to allow knowledge-based optimization and control of these processes.
The 15 CORE ESRs have received academic, industrial and transferable skills training in webinars, at network-wide workshops and during open summer schools. All ESRs had a 1 month visit to an academic network partner getting to know fellow ESRs and get training on a relevant research topic. Many peer reviewed papers of ESRs appeared in print while a further number is submitted and in preparation.
