Understanding process effects on the stability of amorphous form products (recrystallization of amorphous form products)

Aims:
The aim of the project is to understand how various processes influence the stability of drug delivery amorphous form products, in order to limit their recrystallisation. These objectives could roughly be divided into three aspects:
Characterisation of model drug delivery systems, prepared via two different routes, and stored in a range of conditions

Identification of the key molecular factors that affect the stability of the model systems (e.g. designing of experiments)

Development of more general predictive models and molecular fingerprints.

Methodology:
Characterisation of the drug delivery systems is the key aspect of the project. Techniques such as electron microscopy and X-ray diffraction will be used to identify nano-sized crystalline regions within the amorphous state that may initiate re-structuring of the material, and thus lead to product instability. This will allow determination of the size, morphology and structure allowing a tempero-spatial assessment of crystalline areas within the sample. Not only is this process time-dependent but is affected by the type of formulation and processes used to generate the amorphous form. Once reliable methods are developed, a correlation with samples that are developed from different production methods can be developed. The project will also look at simulations and models developed from the characterisation, as they can be utilised to predict formulation properties prior to testing. Predictive models with the established data, would be crucial for predicting the crystallisation of active ingredients and drug delivery systems.
Potential Impact:
The impact of this project will be in areas where an amorphous product is desired, such as with many drugs within medicine. In this instance, if the products are unstable, and crystallise, this may affect the efficacy. In developing methods to identify, then understand and ultimately predict this crystallisation, we will be able to consider the effects of processing and storage conditions.

The CDT in Molecules to Product has the potential to make a real impact as a consequence of the transformative nature of the underpinning 'design and supply' paradigm. Through the exploitation of the generated scientific knowledge, a new approach to the product development lifecycle will be developed. This know-how will impact significantly on productivity, consistency and performance within the speciality chemicals, home and personal care (HPC), fast moving consumer goods (FMCG), food and beverage, and pharma/biopharma sectors.
UK manufacturing is facing a major challenge from competitor countries such as China that are not constrained by fixed manufacturing assets, consequently they can make products more efficiently and at significantly lower operational costs. For example, the biggest competition for some well recognised 'high-end' brands is from 'own-brand' products (simple formulations that are significantly cheaper). For UK companies to compete in the global market, there is a real need to differentiate themselves from the low-cost competition, hence the need for uncopiable or IP protected, enhanced product performance, higher productivity and greater consistency. The CDT is well placed to contribute to addressing this shift in focus though its research activities, with the PGR students serving as ambassadors for this change. The CDT will thus contribute to the sustainability of UK manufacturing and economic prosperity.
The route to ensuring industry will benefit from the 'paradigm' is through the PGR students who will be highly employable as a result of their unique skills-set. This is a result of the CDT research and training programme addressing a major gap identified by industry during the co-creation of the CDT. Resulting absorptive capacity is thus significant. In addition to their core skills, the PGR students will learn new ones enabling them to work across disciplinary boundaries with a detailed understanding of the chemicals-continuum. Importantly, they will also be trained in innovation and enterprise enabling them to challenge the current status quo of 'development and manufacture' and become future leaders.
The outputs of the research projects will be collated into a structured database. This will significantly increase the impact and reach of the research, as well as ensuring the CDT outputs have a long-term transformative effect. Through this route, the industrial partners will benefit from the knowledge generated from across the totality of the product development lifecycle. The database will additionally provide the foundations from which 'benchmark processes' are tackled demonstrating the benefits of the new approach to transitioning from molecules to product.
The impact of the CDT training will be significantly wider than the CDT itself. By offering modules as Continuing Professional Development courses to industry, current employees in chemical-related sectors will have the opportunity to up-skill in new and emerging areas. The modules will also be made available to other CDTs, will serve as part of company graduate programmes and contribute to further learning opportunities for those seeking professional accreditation as Chartered Chemical Engineers.
The CDT, through public engagement activities, will serve as a platform to raise awareness of the scientific and technical challenges that underpin many of the items they rely on in daily life. For example, fast moving consumer goods including laundry products, toiletries, greener herbicides, over-the-counter drugs and processed foods. Activities will include public debates and local and national STEM events. All events will have two-way engagement to encourage the general public to think what the research could mean for them. Additionally these activities will provide the opportunity to dispel the myths around STEM in terms of career opportunities and to promote it as an activity to be embraced by all thereby contributing to the ED&I agenda.