Reverse anti-solvent membrane crystallisation can produce the submicron sized drug particles required for long-acting injectable formulations through the unparalleled control of solvent mixing that is both precise and scalable. This disruptive technology mitigates the solid-state changes and particle size variability associated with historic drug production approaches to catalyse the development and manufacture of long-acting injectable medicines that are critically important to a wide range of treatments. The PhD candidate will work closely with the industrial sponsor (GlaxoSmithKline, GSK) and academic partners to develop this technology, including secondment into GSK, which may include on-site testing of the developed membrane crystallisation process at GSKs campus. The candidate will receive an attractive financial package (£17.7K/annum (tax free) bursary; UK fees paid*) from sponsors EPSRC and GSK.
Submicron sized drug particles with narrow size distributions are a prerequisite of long acting injectables, influencing the pharmacokinetic profile and inflammatory response. Achieving this particle size by first intent through traditional batch crystallisation processes is inherently difficult due to a tendency towards growth dominated kinetics. “Bottom-up” methods can be employed to produce submicron particles by first intent but the techniques (e.g. spray drying, or supercritical fluid precipitation) are difficult to scale or incredibly costly to operate. Therefore, manufacturability is a substantial barrier to the production of drug particles within this specific particle size range, which can impede progression of long-acting injectable medicines.
Precipitative approaches provide a much simpler method to “bottom-up” submicron particle production by driving through incredibly high supersaturation during crystallisation. A “reverse” addition of active pharmaceutical ingredient (API) dissolved in solvent is added to excess anti-solvent resulting in a nucleation dominated crystallisation. Fast and uniform mixing is critical to delivering narrow particle size distributions. However, current technological approaches are often characterised by poor control of mixing between the solvent and anti-solvent phases, which makes dosing rate challenging to regulate and leads to poor control over the supersaturation profile. This regularly results in agglomeration of solids or amorphous products.
Membrane crystallisation introduces a microporous membrane that separates the antisolvent from the API containing solvent. The membrane incorporates well defined interfacial area with a high porosity, enabling the rate of solvent transfer across the membrane to be precisely controlled. This advances the regulation of supersaturation, thereby improving control over the crystallisation kinetics. The size and size distribution of sub-micron drug particles can therefore be tailored within a well-defined hydrodynamic environment, that can be easily reproduced when scaling up the technology, due to a consistent geometry, and the use of fluid-dynamics that can be well described through existing phenomenological approaches.
By the end of the project, the successful candidate will have helped to develop reverse antisolvent membrane crystallisation (RAMC) as a platform technology to eliminate existing barriers in the production of sub-micron particle size APIs, to enable progression of critically dependent API assets. The combination of science and engineering skills that the candidate will develop, will foster a unique and highly versatile skillset, together with building expertise in a rapidly emerging platform technology. The researcher will be based at Cranfield University to take advantage of their world class experimental research facilities, complete with specialist facilities for the development of membrane crystallisation systems, while working closely with GSK partners, which may include on-site demonstration of RAMC. Both UK and international travel are expected to build professional networks through dissemination of scientific progress to industry and academic audiences.
In addition to an extensive transferrable skills programme on offer at Cranfield, the candidate will work with their academic supervisors to tailor a personal development plan based on experience, and career aspirations. Specific laboratory skills training will be provided. Our aspiration is to train leading research talent, with advanced analytical and communication skills, that will differentiate our finishing candidates from their peers to maximise their success in academia or industry.
Supervisor: Professor Ewan McAdam
Applicants should have a first or second class UK honours degree in chemical engineering, chemistry, pharmacy, pharmacology, environmental engineering, environmental science or a related discipline.
How to apply
For further information please contact:
Name: Professor Ewan McAdam
T: (0) 1234 750111 Ext: 4546
If you are eligible to apply for this studentship, please complete the online application formstating the reference No. SWEE0212