Approximately 60% of oral drug candidates face bioavailability risks. The metastable amorphous state or amorphous solid dispersion (ASD) can enhance bioavailability, however introduces a heightened risk of physical instability.

Current methods for identifying a suitable amorphous form for bioenhancement rely heavily on trial and error and characterisation only identifies failure after the fact, rather than being able to design a formulation to be predictably stable. Standard characterization techniques (XRPD, thermal analysis, Polarised Light Microscopy) offer limited structural insights and only confirm issues after crystallization has occurred. Alternative spectroscopic and scattering techniques can provide structural information and earlier identification of instability, though confirmation of their value to accelerating the drug development process is yet to be confirmed.
Here, the combination of high throughput experimentation and advanced characterisation to increase the speed of identifying and assessing the stability of amorphous solid formulations for clinical development will be explored.

Research questions

The key research questions are as follows:

• can characterisation techniques such as low frequency Raman/terahertz spectroscopy, ss-NMR and X-Ray Pair Distribution Function give improved sensitivity to detection of amorphous instability and understanding of long term stability?
• can high throughput and materials sparing analysis of amorphous solid forms result in the faster identification of a bioavailable formulation?
• can the data and fundamental learnings be used to computationally predict a stable and bioavailable formulation?
• does the extra characterisation drive further understanding of variability seen in bioavailability of amorphous materials (such as batch to batch variability; impact of different routes to amorphisation?)
• how does the manufacturing route to form the amorphous solid dispersion impact the stability and performance.

The exploration of spectroscopic and scattering characteristation, combined with high throughput automation, on amorphous forms is currently underexplored. These techniques and therefore this collaboration is required to adequately explore these research areas. 

Outline of activities

You will learn strategies to generate amorphous pharmaceutical materials and characterise them. You will use different approaches to generate amorphous materials (such as spray drying, hot melt extrusion, solvent evaporation approaches) and generate a fundamental understanding of differences in stability and physical properties as a function of these approaches.

You will explore a range of characterisation which can reveal the structural nature of amorphous materials and their interaction with polymers (as relevant). This work will be set within the context of accelerating the assessment of the long term stability of these materials for pharmaceutical development. As appropriate, models will be used to understand the structural nature of these materials.

Finally, you will explore the impact of formulating these materials and whether the methods developed can be extrapolated to stability assessment of the final formulated product.

You will be trained in practical and theoretical aspects of structural characterisation, pharmaceutical solid form development and formulation.

Further information

Further funding will be required for international applicants.