Experimental and computational investigation of the stabilisation of drug molecules in their amorphous state by mesoporous polymers

The formulation and delivery of poorly soluble drugs has always been a challenge with estimated 70-90% of molecules in the development pipeline suffering from poor solubility and bioavailability. One way forward is to use an amorphous form of the drug, since this exists in a higher energy state and is more soluble than crystalline forms of the same compound. Amorphous small-molecule drugs, however, are intrinsically unstable and will spontaneously convert to lower-energy crystalline forms with lower aqueous solubility. A current popular approach to attempt to stabilise drugs in amorphous forms is to load them in the cavities of a mesoporous polymer which is then used as the delivery vehicle. Therein, with correct choice of pore size, the dynamic reorganisational requirements for crystallisation are unfulfilled. At present, the precise mechanism(s) for such amorphous state stabilisation is under debate. Computational evidence from our group at Aston indicates that, in addition to the accepted view of the size constraint (spatial confinement) of the pore preventing crystal nucleation, it is also highly influenced by non-covalent interactions between the drug molecules and the pore walls.

This project will comprise a combination of advanced laboratory-based experimental work and computer-based molecular modelling. The aim of this project is to develop a predictive computational approach that will allow the matching of individual poorly soluble drugs to mesoporous materials that will stabilise the drugs in their amorphous state and prevent crystallisation. This will be achieved by building upon the experimental and computational successes in this area achieved by the Aston groups of Dr Dan Rathbone and Dr Ali Al-Khattawi. The behaviour of selected drug molecules and their modes of aggregation in mesoporous materials (cellulose-based and cellulose derivative-based in the first instance) will be modelled using molecular dynamics simulations under a range of conditions (solvents, concentration, temperature). The observed outcomes will be benchmarked against experiments including DSC thermal analysis, HPLC quantification and nitrogen porosimetry.

Supervisors: 

Dr Dan Rathbone, Dr Ali Al-Khattawi

PhD programmes are for those who are seeking to develop greater in-depth knowledge in a specific area. Completing this level of study is about making an original contribution to knowledge, making new discoveries, and developing lifelong skills. 

At Aston University, our Engineering and Physical Sciences PhD programmes will provide all the support and facilities you will need to develop into a leading researcher in your chosen field. You will be welcomed into a supportive community with a shared enthusiasm for original research, where diversity and multidisciplinary is championed.

Person Specification

Candidates should have been awarded, or expect to achieve, EITHER:

• A Bachelors degree in a relevant subject with an award of First Class or 2.1. 

OR 

• A Bachelors degree in a relevant subject with an award of First Class or 2.1, and a Masters degree in a relevant subject with an award of Merit or higher.

Qualifications from other countries which are considered by Aston University to be equivalent to that described above will be eligible to apply.

Submitting an application

We can only consider applications that are complete and have all supporting documents. Applications that do not provide all the relevant documents will be automatically rejected. Your application must include: 

1. English language copies of the transcripts and certificates for all your higher education degrees, including any Bachelor's degrees.
    
2. A Research Statement detailing your understanding of the research area, how you would approach the project, and a brief review of relevant literature. Be sure to use the title of the research project you are applying for. There is no set format or word count. 
    
3. A personal statement which outlines any further information which you think is relevant to your application, such as your personal suitability for research, career aspirations, possible future research interests, and further description of relevant employment experience. 
    
4. Two academic referees who can discuss your suitability for independent research. References must be on headed paper, signed and dated no more than 2 years old. At least one reference should be from your most recent University. You can submit your references at a later date if necessary. 
    
5. Evidence that you meet the English Language requirements. If you do not currently meet the language requirements, you can submit this at a later stage. 
    
6. A copy of your passport. Where relevant, include evidence of settled or pre-settled status.

Interviews

Interviews will be conducted online via Microsoft Teams. If you are shortlisted, you will be contacted directly with details of the interview.  

Studying a PhD is great route into academia and industries that are centred on research and innovation. Areas with a demand for very high level and specialised research skills often demand PhDs.

In addition to this specialist knowledge, PhD education will help you to develop a set of valuable transferrable skills. The very nature of studying an intensive research degree will enable you to become a team player, develop problem-solving skills, analytical thinking, and advanced presentation and communication skills.

The variety of PhD project topics at Aston means that the destinations of our graduates vary substantially. Some choose to continue into academia, at either Aston or other leading institutions, while others go onto use their newly acquired skills in a range of research, healthcare, industry or charitable fields. When selecting your chosen PhD path at Aston, your supervisor will be able to provide you with relevant career opportunities that could be available to you in your specialist area.