Functionalized Materials for Continuous API Manufacturing

The goal of this project is to allow the applicant to develop the qualification as a professor in the field of "Pharmaceutical Engineering" with special focus on heterogeneous catalysis, separation and continuous manufacturing of pharmaceutical ingredients. Active pharmaceutical ingredients (APIs) are the active components of drugs, which are mixed with excipients that modify the behavior of the drug. APIs are classified as small molecules (with molecular weights greater 1000) and large molecules, such as polypeptides, proteins and other large biological molecules. While small molecules are often made via synthetic or semi-synthetic pathways, large-molecule drugs are exclusively manufactured using genetically modified organisms or mammalian cell lines. The syntheses of small-molecule drugs are usually multistep reactions where often more than 97% of all reactants go to waste and must be deposited or recovered, using expensive separation and rework processes. Therefore, there exists a trend to synthesize APIs via highly selective processes. Thus, selective, active and stable catalysts play an important role in pharmaceutical manufacturing, effectively replacing stoichiometric routes of synthesis. In this context there is an increasing interest using heterogeneous functionalized materials because they have many advantages, such as ease of separation, reusability, etc. After the synthesis the APIs have to be purified. In the case of small-molecule drugs this is often done via crystallization. The purification and recovery of larger molecules, such as biosynthetic products, is carried out by downstream processing, involving several purification and recovery steps. Downstream processing is a significant cost factor and may become a bottleneck for the industrial implementation. In order to develop effective and costefficient chromatographic processes, again functionalized materials are needed. Thus, the rational design and tailoring of functional surfaces is a key step for many applications in the pharmaceutical and fine chemical industry. Another aspect of modern pharmaceutical manufacturing is the implementation of continuous processes, which - in contrast to current batch technology - may offer significant benefits. Therefore, the goals of this project are the development, the characterization and the computational analysis of various new functionalized surfaces and materials that can be used for the synthesis and purification of APIs in continuous operation mode. In particular, the applicant will focus on: 1. The synthesis and development of novel chiral titanocenes and Pd-complexes. 2. The covalent immobilization of the catalytic active compounds on a. H-terminated Si-particles b. Functionalized silica-gel and cellulose particles c. H-terminated and cellulose-functionalized wafers 3. The preparation of functionalized silica-based monolithic materials and 4. The implementation of the novel functional materials for continuous manufacturing. All in all, by combination of experimental and computational approaches the outcomes of this project will help to prepare and purify APIs easier, more cost effective, and more environmentally friendly.