Recent Progress in Continuous Crystallization

Dear Colleagues,

The recent SARS-CoV-2 pandemic underlines the need for rapid, scalable, and robust operation of pharmaceutical manufacturing systems that permits flexible production of lifesaving drugs quickly and safely when needed. Continuous pharmaceutical manufacturing is encouraged by the world-leading regulatory agencies due to several advantages over batch manufacturing. Potential advantages include a more consistent product quality, improved safety, easier scalability and the resilience of a fully automated end-to-end production system. In contrast, batch-wise production is characterized by intermittent operation and often intercontinental shipping of intermediates. Crystallization not only separates and purifies the intermediates/final drug substance in each synthesis step, but also constitutes the bridge between the synthesis of the drug substance and the final product formulation in terms of polymorphs, particle size distribution, shape, and so on. Therefore, it has an indispensable role in a fully continuous, integrated pharmaceutical manufacturing system. The increasing number of industrial applications and journal publications underlines the high attention on this topic, which motivates the current Special Issue.

The aim of this Special Issue is to capture the most recent advances and innovations in the area of continuous pharmaceutical crystallization. Industrial applications involving process development for real APIs at any scale is the main focus. Furthermore, work on fundamental advancements is also warmly welcomed. Topics of interest include, but are not limited to:

• Fundamentals of crystallization kinetics and thermodynamics, impurity rejection, phase diagrams, and liquid–liquid phase separation;
• Development and application of process analytical technology (PAT) and innovative monitoring strategies;
• Multivariable data analysis and machine learning in complex monitoring systems;
• Advanced control methods;
• On-line fault diagnosis, troubleshooting and predictive maintenance with particular focus on fouling issues and antifouling strategies;
• Integration with upstream (e.g. reaction) and downstream (e.g. filtration and drying) processes;
• Application of quality by design (QbD) and quality by control (QbC) approaches for the design of innovative crystallization systems;
• Integration with particle size and shape manipulating steps, including ultrasound, wet-milling and spherical agglomeration;
• CFD simulations for process scale-up;
• High throughout crystallization screening, solvent selection, and design;
• Techno-economic optimizations, environmental impacts;
• Industrial case studies of integrated continuous pharmaceutical processes.

We are pleased to invite you to contribute to this Special Issue in form of a review paper or original research article.

Dr. Botond Szilágyi
Dr. Qinglin Su
Dr. Richard Lakerveld
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. ChemEngineering is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• innovative pharmaceutical crystallizers
• advanced monitoring systems
• risk assessment
• fault diagnosis
• predictive maintenance
• model-based crystallization engineering
• nucleation control
• miniaturized technologies
• system integration