Crystallization Workshop in Torino, Italy

Presentation abstract:
This presentation will dive into topics such as how to measure solubility, metastable zones, induction times and more.

Speaker bio:
After a long career in academia (TU Delft, University of Strathclyde, University of Rouen), Joop H. ter Horst crossed over to industry. He currently works at Tiofarma, a small pharmaceutical company in the Netherlands. He leads a small research group that translates formulations into Tiofarma's manufacturing processes. 

Presentation abstract:
Crystallization processes, challenges and opportunities will be highlighted with focus on the pharmaceutical industry demands and on the scale-up and downstream stages.

Speaker bio:
Ana Cruz joined Hovione’s Process Chemistry Development team in 2009 to work on the development of chemical processes for manufacturing Active Pharmaceutical Ingredients (APIs). She graduated in Applied Chemistry from the Facultity of Science and Technology of Lisbon (FCT-UNL) in 2004, followed by a PhD in Organic Chemistry at the University of Bath with Professor Michael Willis sponsored by EPSRC and GSK. Her current main interests are related with the development of innovative and robust processes for API manufacture, focusing on green chemistry, catalysis and modelling approaches.

Presentation abstract:
This presentation will delve into the intricate world of pharmaceutical crystallisation, where the scarcity of material poses a significant challenge. Our journey begins with small-scale experiments designed to yield valuable thermodynamic and kinetic data despite limited resources. We then explore how this valuable data, coupled with modeling tools, pave the way for scaling up experiments. The essence of our discussion will explore the strategic integration of this data into scalable crystallisation processes, ultimately leading to practical solutions in commercial pharmaceutical manufacturing.

Speaker bio:
Dr. Kirstie Milne is a senior scientist within the Particle Engineering Community at AstraZeneca. Following a PhD specialising in zeolite crystallisation for application in oxidation catalysis, has gained 4.5 years of experience within late-stage crystallisation development for small molecules, API scale-up and manufacture, and specializing in working at the drug product interface. They actively pursue sustainability initiatives in their work, reflecting a passion for environmentally conscious R&D and manufacturing.

Presentation abstract:
Particle morphology can be a real challenge for mixing, filtration, and downstream processes, like milling or formulation. Spherical crystallization can enhance bulk properties to overcome these issues. Spherical crystallization occurs by addition of an immiscible solvent (bridging liquid) to the process solvent(s), which induces aggregation of the crystals into spherical agglomerates. The choice of the bridging liquid is preponderant in the success of spherical crystallization, i.a. miscibility, solubility and wetting ability towards the crystals, toxicity. A workflow has been developed to identify a suitable bridging liquid and assess the liquid-liquid phase diagram at mL scale prior to any scale-up investigation.

Speaker bio:
Manuel Henry received his engineer’s diploma in chemistry and chemical engineering from the engineering School CPE in Lyon, France in 2002. Then, he completed a PhD on the application of PAT to industrial crystallization at LAGEP (University Lyon I, France) in collaboration with Sanofi-Aventis in 2006. After a Post-Doc on in-line spectroscopy applied to different chemical processes (drying, polymerization…) in an analytic lab of the CNRS (French research organisation), he joined Boehringer Ingelheim in 2009 in the chemical development department in Biberach (Germany) to improve crystallization knowledge at early stage. Manuel is now leading a laboratory with 3 coworkers with as main activities: solubility measurement, form screening, crystallization optimization and troubleshooting for intermediates and final APIs.

Presentation abstract:
Multiphase systems such as emulsions and foams are commonly used to tailor food functional properties such as texture, mouthfeel and taste. These systems can be stabilized with surfactants or, as recently demonstrated, by solid particles through the so called Pickering effect. In my talk I will describe how crystal engineering principles and tools, both computational and experimental, can be used in the design of optimal Pickering crystals and multiphase systems.

Speaker bio:
Dr Elena Simone obtained her BSc and MSc in chemical engineering from the University of Pisa (Italy). After a short period as research assistant in Unilever R&D (Colworth, UK), in 2012 she started her PhD in Chemical Engineering at Loughborough University (UK). She graduated in 2015, and after a short postdoc between Loughborough and Purdue University (US), in 2016 she joined the school of Food Science and Nutrition at the University of Leeds (UK), as lecturer in Food Crystal Engineering. Since 2021 she has been associate professor and then professor (from 2024) in chemical engineering and European Research Council fellow at Politecnico di Torino (Italy).

Presentation abstract:
When thinking about APIs solid forms, our mind always goes to their impact on the API bioavailability or, looking at the Generics market, to their use to circumvent the Originators’ patents. However, solid forms can often give access to easy solutions to complex problems. Indeed, old molecules still have a lot to tell concerning their solid form landscape, and “old”, overlooked solid forms too may regain fame by solving current issues. We’ll discuss case studies where recent and less recent APIs solid forms can ease manufacturing operations and solve purity issues, going from new solid forms of “new” drugs, new solid forms of old drugs, and old solid forms of old drugs.

Speaker bio:
Michele Baldrighi obtained his PhD in Politecnico di Milano, Italy, working on pharmaceutical cocrystals. After a few years as Post-Doc both in Politecnico di Milano and at the Italian Institute of Technology, he moved to the API manufacturing Industry field. Since 2018 he is responsible for R&D solid state activities in Industriale Chimica (Chemo group). From 2022 he is coordinator for solid state and particle properties teams for Industriale Chimica and ChemoBiosynthesis, the two Italian Chemo Group’s API manufacturing Companies.

Speaker bio:
Philippe Fernandes is an accomplished Associate Director at The Janssen Pharmaceutical Companies of Johnson & Johnson, with over 20 years of experience. Based in Belgium, he leads small molecule drug development, covering areas such as Cardiovascular & Metabolism, Immunology, Infectious Diseases, Neuroscience, Oncology, and Pulmonary Hypertension. He excels in developability assessment, solid-state control, extending to crystallization development. Philippe oversees a team of 16 employees, guiding over 50 projects. He is an innovation leader in solid-state informatics and collaborates with academic institutions to advance pharmaceutical research.

Presentation abstract:
This presentation will cover several top-level examples of industrial crystallization processes and how Crystal16 is used as tool for this purpose. It will showcase how Crystal16 data are used in combination with other, e.g. thermo analytical data, and speak about the importance of solubility profiles during process development.

Speaker bio:
Marco Rudolf von Rohr started his chemical career 2009 as a lab technician, taking care of synthesis of small molecules and peptides. Some years later, he studied industrial chemistry at the university of applied sciences in Zurich and got his bachelor’s degree in the field of physical chemistry. His first employer after graduation was Switzerland-based CARBOGEN AMICS AG, where he still works, now in his ninth year. Marco started in production department learned a lot about hands-on chemical production, up to 630 L pilot scale. After this short-term production period he moved to the R&D department, where he was most of the time occupied with process familiarization and up-scaling questions. 5 years ago, Marco moved from daily business small molecule R&D to CARBOGEN AMCIS’ specialists team. He started to intensively work on crystallization development and the profound characterization of solid phases. The most common challenges during his time in this team, became evident during up-scaling. So, Marco's work is, unsurprisingly, strongly associated with technical questions. He would describe himself as some sort of chemical engineer in the field of solid state chemistry.

Presentation abstract:
We are used to thinking of crystallization as a process involving a the solid-liquid interface, being the liquid a solution or a melt. But we also know that crystallization can occur and be stimulated in a soft medium like a gel, via sintering in the case of hard particles, as the result of a chemical vapour deposition process, and so on. In our molecular crystal engineering field we crystallize our systems directly in the solid state, via controlled mechanochemistry with or without appropriate small amounts of solvent, slurry and vapour digestion (i.e., solvent mediated methods), cooling/heating, even photo-irradiation. Our goal is that of obtaining crystalline solids, within the frame of a more sustainable chemistry.

In this presentation, a few selected examples will be shown of crystalline materials obtained via solid state techniques.

Speaker bio:

• Fabrizia Grepioni is Full Professor of General and Inorganic Chemistry at the University of Bologna.
• Scientific interests : molecular crystal engineering (design, synthesis, investigation and applications of molecular crystalline materials).
• Scientific activity: more than 400 papers in peer-reviewed international journals and books; more than 70 communications and lectures at national and international meetings and schools.
• Co-organization of 12 International Workshops on Crystal Forms. The latest edition was held in Bologna in September 2023, and involved 130 scientists from universities and pharmaceutical companies from all around the world.
• Co-founder (2005) of the company PolyCrystalLine S.p.A., which is specialized in solid-state problems involving polymorphs, solvates/hydrates, co-crystals and salts, especially concerning APIs.