EPSRC EngD in Granulation of pharmaceutical formulations

Centre for Formulation Engineering, Dept of Chemical Engineering

University of Birmingham

Granulation of pharmaceutical formulations

EPSRC sponsored Engineering Doctorate project.

Bristol Myers Squibb ( Wirral )

Dr Phil Robbins ( Chemical Engineering, University of Birmingham )

Fees paid plus a tax free bursary of £ 19,600 p.a.

Bristol-Myers Squibb is a leading global Pharmaceutical Company. It is active in developing and marketing novel therapies in the areas of cardiovascular health, cancer, antiviral treatment and mental illness, amongst others. In the past few years it has had eight approvals for new medicines and has an active pipeline, with expectations for several more approvals. Last year it had a research budget of $2.2 billion. The majority of medicines under development at Bristol-Myers Squibb are intended for oral administration. It is necessary in the development of most oral dosage forms (tablets or capsules) to perform a granulation, an intervention which increases particle size. This improves the homogeneity of the system, and facilitates further processing (e.g. tableting) by improving the flow and processability of the formulation.

During the past decade granulation preferences have moved from ‘wet’ granulation, the multiple steps of which require solvents and/or large amounts of energy (which, in addition to increasing cost and adding to the environmental footprint of the system, can contribute to formulation instability), to ‘dry’ granulation, whereby the formulation is processed using ‘roller compaction’ to form a compressed ‘ribbon’ of material followed by subsequent size reduction to produce the granules for further processing.

This project will investigate scalable roller compaction processes, including material input parameters, ribbon quality, granule strength following granulation and tablet properties. The project will also look at the development of scalable analytical processes, i.e. analytical systems that can be applied at scale and operate under the conditions of ‘full’ manufacture, to study these parameters and the possibility for feedback mechanisms to improve or control quality. The formation of the ribbon in the roller compaction process requires an even flow of powder into the ‘nip’ between the rollers and rapid particle rearrangement in the compaction region. It is also necessary to ensure that there is no adhesion of powder to the rollers. These processes influence the scalability of the material and interchangeability of equipment.

In many formulations a lubricant material is added to the dry mix prior to roller compaction. The choice, and level, of material for this process is normally an empirical process, without an investigation of the overall effects the choice will have throughout the lifetime of the formulation, and without reference to the ‘scalability’ of the addition process.

The project will involve:

• The development of analytical techniques to study roller compaction which can provide understanding of the fundamental processes involved, and their relevance to active projects.
• The development and implementation of PAT (Process Analytical Technology) techniques, including multivariate processing models, which will identify those formulations with the optimum characteristics for processing. Acoustics technique will be investigated in the first instance
• Identify techniques which may offer opportunity for feedback control of ribbon quality
• Identify which materials in the formulation armamentarium are best suited to lubrication of roller compaction processes, as opposed to those which are better suited to tablet lubrication
• Investigate the above at scales from 10g to, potentially, tens of kilos.

In order to be eligible for EPSRC funding candidates must have at least a 2(1) in a relevant science or engineering discipline plus is a U.K. national. Applications from candidates with 2(2) and a MSc or substantial relevant industrial experience are also welcome. Applications from EU nationals are welcome provided they have been working / studying in the UK for three years and have a relevant equivalent degree. Applicants should email their c.v. to r.w.greenwood@bham.ac.uk