Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

Humans are rhythmic beings, with daily sleep/wake cycles affecting almost every aspect of physiology and behaviour. Our master circadian clock is known to reside in the suprachiasmatic nuclei (SCN) of the hypothalamus. Via multiple pathways, output from the SCN synchronizes peripheral oscillators throughout the body. The discovery of the molecular components of the core clock has provided new insight into the link between circadian biology and chronic diseases, but has not been exploited for drug discovery. With this work we will prepare chemical probes for the clock proteins REV-ERBalpha and RORalpha, characterise their activity in models of inflammation, and deliver lead optimised molecules for clinical development.

Solid dose forms are the backbone of many manufacturing industries. In pharmaceutical therapeutics, tablets, capsules, dry powder inhalers and powders for re-suspension cover the vast majority of the £5.6Bn sales by this industry in the UK. Food (sales £67Bn) is the single largest industry of the UK manufacturing sector which totalled £365Bn sales in 2014 (Office of National Statistics). In all these manufacturing processes and in final use, the physical behaviour of the powder is at least as important as the chemistry. Stability, weight and content uniformity, manufacturing difficulties and variable performance are determined by decisions made during the formulation process Manufacturing problems are ubiquitous; the Rand report (by E.W. Merrow, 1981) examined powder processes and found on average 2 year over-runs to get to full productivity, and development costs 210% of estimates, due to incompatibility between powder behaviour and process design. In the intervening years, plant engineering techniques have developed, but the rationalisation of formulation decisions has never received more than cursory, empirical study. This project proposes to develop a Virtual Formulation Laboratory (VFL), a software tool for prediction and optimisation of manufacturability and stability of advanced solids-based formulations. The team has established expertise in powder flow, mixing and compaction which will be brought together for the first time to link formulation variables with manufacturability predictions. The OVERALL AIMS of the project are (a) to develop the science base for understanding of surfaces, particulate structures and bulk behaviour to address physical, chemical and mechanical stability during processing and storage and (b) to incorporate these into a software tool (VFL) which accounts for a wide range of material types, particle structures and blend systems to enable the formulator to test the effects of formulation changes in virtual space and check for potential problems covering the majority of manufacturing difficulties experienced in production plants. The VISION for VFL is to be employed widely in the development process of every new formulated powder product in food, pharmaceuticals and fine chemicals within five years of the completion of this project. VFL will consider four processes: powder flow, mixing, compaction and storage; and will predict four manufacturability problems: poor flow/flooding, segregation/heterogeneity, powder caking and strength/breakage of compacts These account for the majority of practical problems in the processing of solid particulate materials The OVERALL OBJECTIVES of the project are: (a) to fill the gaps in formulation science to link molecule to manufacturability, which will be achieved through experimental characterisation and numerical modelling, and (b) establish methodologies to deal with new materials, so that the virtual lab could make predictions for formulations with new materials without extensive experimental characterisation or numerical modelling. This will be achieved through developing functional relationships based on the scientific outcomes of the above investigations, while identifying the limits and uncertainties of these relationships.

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.