Investigation into the characteristics of crystal dissolution and growth through surface chemistry and mass transfer in the boundary layer

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


The performance of a drug is dependent on the bioavailability of the API (Active Pharmaceutical Ingredient). In the case of many oral drugs, this is influenced by its dissolution characteristics. Indeed, dissolution is usually tested throughout a drug's development lifetime. Currently, the Noyes-Whitney model is used in most cases, which only considers the difference in the bulk concentration and the concentration at the solid-liquid interface. This model makes several assumptions about the concentrations involved and fails to consider the surface chemistry. It would therefore be useful to make more accurate predictions about a substance's solubility based on its material characteristics to expedite the drug development process. For instance, it may help influence decisions on the dosage composition. This will require gaining a better understanding of the kinetics of dissolution on a fundamental level.

Ideally, a material's dissolution characteristics would be determinable using only knowledge of its surface chemistry (including how this varies between different faces) and how its interaction with the solvent molecules. Though this may not be entirely achievable, it is still worth exploring new ways of predicting a substance's dissolution behavior.

A key aspect in this research is gaining a better understanding of the face specific dissolution rates of single crystals, so that theories regarding surface energy interactions can be validated. To achieve this, it will be necessary to employ various techniques, such as Mach-Zehnder and Michelson interferometry, as well as optical microscopy to observe any changes in the crystal morphology. Additionally, it is also worth looking at differences in dissolution between different crystal structures (e.g., form I and II of Paracetamol), to determine how this may influence the overall efficacy of drug formulations.

Planned Impact

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.


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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/S022473/1 01/04/2019 30/09/2027
2746217 Studentship EP/S022473/1 01/10/2022 30/09/2026 Thomas Barker