Engineering Downstream Processes to Enhance Processability of Crystallized Products

What is the PhD Project About?

This project, performed in collaboration with AstraZeneca, will address one of the key challenges in processing pharmaceutical products. In the production chain of active pharmaceutical ingredients (API), a crystallization step is an integral part for separation and purification purposes. A typical solution crystallization step is followed by the so-called downstream processing steps. These correspond to a solid-liquid separation step, i.e. filtration, a washing step to remove the mother liquor from the filter cake, and finally a drying step to evaporate the wash solvent. The dried powder is eventually blended with excipients and in some cases formulated as tablets or granules to obtain the final solid product. The performance of these steps is often dictated by the crystallization step, namely through the particle size and shape distribution (PSSD), the moisture content, the surface properties (e.g. cohesive/adhesive interactions), to name a few, of the crystallized product. The aforementioned downstream steps have been studied both experimentally and computationally in detail for many different applications. Experimental and modeling studies that aim to provide an empirical relationship between the PS(S)D (mostly on size and rarely on shape) and the final filter cake porosity have been reported. Despite the significance of PSSD, washing and drying have been scarcely explored over the years, especially in an integrated framework with the upstream crystallization step.

How Will this Challenge be Addressed?

To address the challenge related to engineering downstream processes, we will develop an innovative multiscale research campaign. We will capitalize on the state-of-the-art experimental (microscopic and multiprojection imaging devices, agitated filter-dryer, tomographic devices) and computational tools (population balance equation solvers, parameter estimators, molecular modeling, packed bed models), readily available at the University of Manchester. In particular, we will develop predictive microscopic and macroscopic models backed by experimental data for all the three aforementioned downstream steps (filtration, washing and drying) to improve our understanding and in turn develop efficient processes. These models will pave way to integrate the entire process chain, where given a PSSD one could quantitatively gauge the processability of the crystallized product in terms of both processing time and energy consumption.

Supervisory Arrangements for the PhD Student and the Environment

The PhD student will be jointly supervised by Dr. Ashwin Kumar Rajagopalan, Lecturer and Dr. Carlos Avendaño, Senior Lecturer, both in the Department of Chemical Engineering at the University of Manchester. The project is an industrial CASE studentship, hence the PhD student will also work closely with our industrial project, AstraZeneca with the student spending 3 months at the company site to get exposed to industrial research. The PhD student will also work in a tight collaboration with PhD students and postdoctoral research associates from both the groups. The student will have access to the laboratory facilities of the group in the newly opened Engineering Building (part of the MECD program) at the University of Manchester. The student will also have access to the computational shared facility, a 10000 node cluster and one of the best in the world, to tackle the computational aspects of this project.

What can the PhD Student Expect?

• Disseminate results obtained over the course of the PhD program through prestigious peer-reviewed journals (e.g. Chemical Engineering Science, Chemical Engineering Journal, Crystal Growth & Design, Powder Technology, Separation and Purification Technology, etc.,)
• Attend national (British Associate of Crystal Growth) and international (International Symposium on Industrial Crystallization, American Institute of Chemical Engineering Annual Meeting etc.,) scientific conferences and workshops (EFCE summer schools on crystallization) across the globe to present research findings and network with peers from academia and industry
• Work with a young and growing research group at the birthplace of chemical engineering
• Have the opportunity to collaborate with other research groups working on relevant topics at the University of Manchester
• Have access to several one-of-a-kind experimental and computational tools in the UK, that has the potential to be transferred to an industrial setting in the near future
• Get direct exposure to industrial partners through this project and indirect exposure through projects of other PhD students in the research group
• Obtain a PhD degree on solving classical chemical engineering problems and learn and hone 21st century experimental and computational skills that can be readily transferrable to both an academic and an industrial setting

Entry Requirements

Applicants should have or expect to achieve a first-class honours degree in Chemical Engineering or Process Engineering. Under exceptional circumstances, high 2.1 applicants will be considered.

Application Information

Information about the application process and a link to the online application form can be found at https://www.manchester.ac.uk/study/postgraduate-research/admissions/how-to-apply/.

You MUST make contact with the lead project supervisor before submitting an application.

When completing the application include the name of the lead project supervisor as the potential supervisor.

Enquiries about this project can be sent to Dr Ashwin Kumar Rajagopalan - [Email Address Removed] as the lead project supervisor. Applicants can also visit ash23win.github.io for further information regarding Dr Rajagopalan’s research group. The Admissions team in Chemical Engineering can be contacted at [Email Address Removed] with any queries you may have regarding the application process.

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. We know that diversity strengthens our research community, leading to enhanced research creativity, productivity and quality, and societal and economic impact. We actively encourage applicants from diverse career paths and backgrounds and from all sections of the community, regardless of age, disability, ethnicity, gender, gender expression, sexual orientation and transgender status.

We also support applications from those returning from a career break or other roles. We consider offering flexible study arrangements (including part-time: 50%, 60% or 80%, depending on the project/funder).