University of Bath URSA project: Ultrasound Computed Tomography for Advanced Pharmaceutical Manufacturing

This project is one of a number that are in competition for funding from the University of Bath URSA competition.

Project

This PhD project aims at establishing Ultrasound Computed Tomography (USCT) as an in-line process analytical technology, capable of monitoring, controlling, and studying the crystallization of active pharmaceutical ingredients (APIs) formulated for dry-powder inhalers (DPIs).

Why DPIs? These devices that can transform the way we deliver vaccines, peptides, and other therapies. Additionally, unlike conventional inhalers, DPIs do not use propellants - a major source of greenhouse gas emissions. However, they are unsuitable for advanced applications, due to the wide variability of deposited drug in the lungs caused by the wide particle size distribution of crystals found in formulations.

Why USCT? This robust, non-invasive, non-intrusive technology is based on using acoustic impedance which allows characterizing and producing images of the acoustical distributions. In other words, USCT allows us to listen how pharmaceuticals agglomerate (nucleate), crystallize and grow.

Leveraging USCT’s capabilities, we will monitor and control the manufacture of particles, to generate crystals with controlled polymorphic structures, pre-determined size (2-5µm range) and particle size distribution. In this manner, we will demonstrate that challenging treatments (e.g., antibiotics, antifungals, etc) can be delivered as powder formulations in Dry Powder Inhalers (DPIs)

To initiate the development of this vision and fulfil the aim of this PhD project, the following objectives will be completed:

1.    Implement USCT in a batch cooling crystallization unit and deploy it for digital twin development

2.    Benchmark USCT’s measurements against conventional analytical technologies (microscopy, mastersizer)

3.    Develop artificial intelligence/machine learning (AI/ML) models that integrates the USCT signals with chemoinformatics, enabling the detection of impurities, crystal morphologies and polymorphs.

4.    Produce high-dose antibiotics powders, while exploring their crystallization, isolation, particle formation and product formulation

5.    Estimate the aerodynamic particle size distribution of these formulations when aerosolised from suitable high-dose inhalers

This project is highly interdisciplinary and contains innovations in supramolecular chemistry, chemical engineering, analytical technologies, Artificial Intelligence, and drug delivery; and it will contain the following research activities:

• Develop design of experiment (DOE) protocols for crystallization campaigns.
• Explore crystallization processing, design and control.
• Implement advanced materials characterization techniques (PXRD, DSC, microscopy, NIR, Raman, USCT)
• Develop AI/ML models
• Establish a process assurance and then full process control with USCT imaging data.

Candidate Requirements

Applicants should hold, or expect to receive, a First Class or good Upper Second Class Honours degree (or the equivalent). A master’s level qualification would also be advantageous.

Non-UK applicants must meet our English language entry requirement by February 2023 in order to be considered.

Enquiries and Applications

Informal enquiries are encouraged! Direct these to Dr Bernardo Castro Dominguez - [Email Address Removed]

Please make a formal application should via the University of Bath’s online application form for a PhD in Chemical Engineering

When completing the form, please identify your application as being for the URSA studentship competition in Section 3 Finance (question 2) and quote the project title and lead supervisor’s name in the ‘Your research interests’ section. 

More information about applying for a PhD at Bath may be found on our website.

Funding Eligibility

To be eligible for funding, you must qualify as a Home student. The eligibility criteria for Home fee status are detailed and too complex to be summarised here in full; however, as a general guide, the following applicants will normally qualify subject to meeting residency requirements:

• UK nationals (living in the UK or EEA/Switzerland)
• Irish nationals (living in the UK or EEA/Switzerland)
• Those with Indefinite Leave to Remain
• EU nationals with pre-settled or settled status in the UK under the EU Settlement Scheme.

This is not intended to be an exhaustive list. Additional information may be found on our fee status guidance webpage, on the GOV.UK website and on the UKCISA website.

Equality, Diversity and Inclusion

We value a diverse research environment and strive to be an inclusive university, where difference is celebrated and respected. We encourage applications from under-represented groups. In particular, we are welcoming applications from candidates with Refugee, Asylum Seeker, or Humanitarian Protection in the UK to our Doctoral Sanctuary Studentship in Engineering and Design.

If you have circumstances that you feel we should be aware of that have affected your educational attainment, then please feel free to tell us about it in your application form. The best way to do this is a short paragraph at the end of your personal statement.

The Disability Service ensures that individuals with disabilities are provided the support that they need. If you state if your application that you have a disability, the Disability Service will contact you as part of this process to discuss your needs.

Keywords: Applied Chemistry; Chemical Engineering; Electrical Engineering; Electronic Engineering; Machine Learning; Pharmaceutical Chemistry; Pharmacology; Physical Chemistry; Solid State Physics; Structural Chemistry