Ultramicroscopy of complex materials - IDPC STEM

Lead Research Organisation: University of Leeds
Department Name: Chemical and Process Engineering

Abstract

One of the key challenges currently faced by pharmaceutical product development is the ability to link structure to performance in order to realise the full potential of a drug. At present there are very few techniques available that enable the nanostructure of a medicine to be described at the small length scales involved while accounting for pharmaceutically unusual elements and structures, and also the unknown role of functional excipients.

Our goal in this project is to provide a complete physical description of complex pharmaceutical materials using specialist electron microscopy techniques. We will use electron microscopy (both scanning and transmission EM) to measure and understand the distribution of product components, size of pores and layers etc., then we will utilise the emerging capabilities of integrated differential phase contrast in scanning transmission electron microscopy (iDPC STEM) to investigate the key interfaces in a product at atomic resolution, mapping both light and heavy atoms. Analysis at this ground-breaking scale will enable structure-property relationships to be developed for performance control.

Research in the project fits within the School of Chemical and Process Engineering's expertise in Advanced Engineering Materials, and specifically within the Electron Microscopy and Nanoscale Characterisation research group.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/S513829/1 01/10/2018 30/09/2023
2182593 Studentship EP/S513829/1 01/01/2019 31/03/2023 Natalia Koniuch
 
Description 1) The low-dose transmission electron microscopy (TEM) techniques were developed to directly and indirectly image the crystal lattice of the organic pharmaceutical materials. These findings will help to understand the effect of different crystallisation methods on the presence of crystal defects and to link the structure to the performance.

2) The work has demonstrated the possibility to observe and understand hydration and dehydration of a model channel hydrate, theophylline. For the first time, the metastable unhydrate form of theophylline was imaged and its structure was identified.

3) The multi-modal cryogenic scanning electron microscopy (cryo-STEM) approach was developed to characterise the novel self-assembled polymeric nanoparticles at the single particle level in its native state. We have identified the multi-layered structure of different composition and density.
Exploitation Route Our findings can be used to establish the link between the product structure and performance to provide appropriate physical parameters for mathematical modelling of the diffusion barrier controlling the drug release in the nanoparticles formulation in the future work.
Sectors Agriculture, Food and Drink,Chemicals,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description Our findings have been used to provide a complex physical and chemical characterisation of the novel polymeric nanoparticles system at the single particle level unobtainable by other bulk techniques.
First Year Of Impact 2023
Sector Agriculture, Food and Drink,Chemicals,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Societal