Marie Sklodowska- Curie Actions Postdoctoral Fellowship- Drug Form Technology

Wroclaw Medical University is looking for candidates for the MSCA Fellowships 2021, which are due to become available as part of the Horizon Europe Programme. At this stage, we invite experienced researchers with a PhD (up to 8 years research experience after PhD), who are willing to come to Poland for 2 years, to send us an expression of interest. As soon as the details of the call are announced, we will begin a collaboration with you to draft a winning proposal.

Supervisor: Professor Karol Nartowski, Department of Drug Form Technology

Topic: “Single step synthesis and formulation of pharmaceutical cocrystals via continuous and scalable processes using QbD approach.”

Short description of the project: General Importance: Pharmaceutical cocrystals are promising materials composed of two or more different molecules with at least one drug in the structure. In 2018 The US Food and Drug Administration (FDA) Guidance on Pharmaceutical cocrystals classified cocrystals as APIs, indicating cocrystals as equivalent to polymorphs. This has amplified the commercial interest in cocrystals as it potentially enables to use previous safety and efficacy data in FDA application and registration processes for medicines with new indications, API substitutions or changes in the solid form. Furthermore, this opens new intellectual property opportunities, as the development of novel solid forms of an API may be used to overcome patent protection of commercialised medicines. The increasing interest in the cocrystal research is mirrored in the almost exponential growth of publications and patent applications involving cocrystals in last 20 years. Pharmaceutical cocrystals can improve and modify the physicochemical properties of APIs without compromising their therapeutic benefit, providing an opportunity to control the properties of the pharmaceutical solid through careful selection of their composition (e.g. coformer) and crystal packing. Cocrystals enable to modify important pharmaceutical properties of the materials i.e. stability, compressibility, taste or solubility which can in turn improve drug absorption in the human body. These modifications are attractive from both academic and industrial perspective in designing novel, improved therapies as they do not comprise therapeutic of medicines. Up to date several experimental methods have been developed to synthesise cocrystals with little consistency in the application of proposed experimental protocols. Available research describes experimental pathways of finding new cocrystals with very little attention in selection and development of low energy industrially scalable methods enabling both synthesis and formulation of pharmaceutical cocrystals. For example, extensively used low scale grinding methods for cocrystals synthesis and screening (e.g. liquid or polymer assisted grinding) could potentially be replaced with industrially scalable methods utilising hot melt extrusion (e.g. matrix assisted cocrystallisation) while solvent based crystallisation methods can be developed towards fluid bed granulation or spray drying techniques. Change of paradigm in cocrystal synthesis towards scalable and industrially acceptable methods can facilitate industrial development of novel pharmaceutical materials and shift highly promising pharmaceutical cocrystals from laboratory bench to bedside. Aims and outlook: The proposed project aims at development general approach for continuous and single step processes enabling to synthesise and formulate pharmaceutical cocrystals as ‘ready to use’ raw materials (e.g. granules and blends) for direct compression or to be packed in capsules or sachets with aid of Quality by Design methods. This will be achieved via systematic investigation of model cocrystal systems for which industrially scalable single step processes (hot melt extrusion, fluid bed granulation and spray drying) will be developed (all facilities available for the applicant at Department of Drug Forms Technology, Wroclaw Medical University). The main focus will be on the interplay between physicochemical parameters of model cocrystals (i.e. solubility in water and pharmaceutically acceptable organic solvents, melting temperature), selection of excipients (e.g. polymers and additives) and processing parameters enabling for successful synthesis and formulation of pharmaceutical cocrystals as raw materials for large scale pharmaceutical processes (e.g. tabletting). Both structure of obtained materials and their pharmaceutical performance will be thoroughly evaluated using state-of-the-art complementary analytical techniques. These include X-ray diffraction, spectroscopic analysis (IR, NMR), calorimetric measurements, dissolution testing and compressibility. More specifically, the applicant aims to establish general protocols for continuous and single step synthesis and formulation of pharmaceutical cocrystals using mechanochemical (hot melt extrusion) and solvent based methods (fluid bed granulation, spray drying). These include (i) selection of technological processes that enables successful cocrystal synthesis based on properties of drug and coformer (e.g. melting point and solubility); (ii) establishing critical process parameters (e.g. process time and temperature, mixing speed, solvent flow) of importance for robust synthesis and formulation of the high quality cocrystals using QbD approach, (iii) providing analytical toolbox (including PAT methods) for characterisation of cocrystal based formulations obtained via continuous and single step processes.Value of proposed research and fit for the project: Development of continuous and single step methods for synthesis and formulation of pharmaceutical cocrystals pose a significant technological and analytical challenge as it requires unique combination of expertise in crystallography and materials science as well as extensive knowledge in pharmaceutical formulations and processes. With formulation expertise and available infrastructure (hot melt extruder, fluid bed granulator, spray drier) Department of Drug Forms Technology at Wroclaw Medical University (PI, dr hab. Karol Nartowski) is unequally placed for successful advancement in scalable technologies enabling for continuous and single step cocrystals synthesis and formulation, allowing to investigate critical aspects of both cocrystals formation and formulation in a single research project and how these scalable processes affect pharmaceutical performance of the final product. The proposed project will established multidisciplinary training platform for two early career researchers in the extensively advancing field of continuous and single step pharmaceutical processes using novel and highly promising pharmaceutical materials enabling them to grow as next-generation scientists. This will support the pharmaceutical formulation science as major strength of European. With extensive international collaborative links of the Department of Drug Forms Technology (PI has long lasting collaboration with University of Innsbruck and University of East Anglia) both early career research scientists will have opportunity to interact with international group of scientists with different expertise in pharmaceutical research from materials science and crystallography to solid state spectroscopy and formulation science providing both candidates with transferrable skills in pharmaceutical formulations.

Send your expression of interest along with your CV to: karol.nartowski@umed.wroc.pl

If you have any questions, please contact the programme coordinator at: maria.wolkowinska@umed.wroc.pl