Insights into surface structural dynamics for particle property control

Interactions between organic particles leads to a phenomenon known as aggregation. Aggregation of proteins and peptides in vivo result in diseases, or in pharmaceutical formulations make products highly unstable during processing and storage. On the flip side, aggregation can also be used to improve properties of small molecule crystals that adopt an undesirable morphologies and to facilitate microencapsulation of drugs into biodegradable polymers. Empirical studies of aggregation have so far enabled a degree of control of the phenomenon. However, a better fundamental understanding of the chemical nature and structural dynamics at the surface of these particles will aid predictive process control and improve our general understanding of diseases.
This can be achieved by using a combination of techniques that provide information on the shape and size of the particles, the chemical functional groups that are present at the particle surfaces and those that are active at interfaces between two media or materials such as in mixed-solvents or in the presence of polymers in the media; as well as the statistically-relevant local structural dynamics at surfaces and interfaces.
Aim: To understand the effect of surface functionalisation on particle aggregation and properties, through state-of-the-art analytical method development.
Objectives:
- To carry out in situ small angle X-ray scattering and polarised Raman spectroscopy to study aggregation.
- To develop methodology to establish the nature and orientation of surface functional groups on particles on immobilised surfaces and in solution using polarised Raman spectroscopy.
- To develop a methodology for the use of electron pair distribution function analysis for the study of organic (bio-) active pharmaceutical ingredients (API) in organic solvents.
The project will develop methodologies for in situ aggregation studies using polarised Raman spectroscopy and small angle X-ray scattering. Although this project requires relatively complicated mathematical modelling of Raman scattering data, method development to enable this technique to be used in situ will help realise its potential as a routine process analytical technology. It will also explore the use of electron pair distribution function analysis for the study of cryo-frozen aggregates. Methods developed here will mitigate effects of radiolysis and beam drag that usually makes organic materials challenging to study under an electron beam.
The proposed project lies within the remit of the EPSRC's portfolio 'Manufacturing The Future' and more specifically 'Particle technologies' and, goes hand-in-hand with EPSRC's prosperity outcomes of a 'Productive Nation' as well as a 'Healthy Nation', having direct implications to pharmaceutical manufacturing and their interactions under in vivo conditions.