BACKGROUND AND IMPORTANCE
Pharmaceuticals contribute £6b annually to the UK economy and most of the products concerned are manufactured in the UK. Pharmaceutical formulations are fixed early during product and process development when only a small quantity of the active ingredient is available. Adhesion of fine powders to metal surfaces creates a currently unpredictable problem which manifests at full-scale production, when it is too late to make changes to formulations and processes for regulatory reasons.
Research of adhesion includes visual observation (Reed et al. 2015, Bakar et al. 2007, Simmons and Gierer 2012) or weighing the material adhered to the punches (Mullarney et al. 2012). Mechanical characterisation methods were proposed, ranging from instrumented punches for the adhesion force with tablets (Waimer et al. 1999) to measurements using a compaction simulator (Wang et al. 2004); and adhesion was also related to high radial stress in the die (Hamid and Betz 2012). At particle level atomic force microscopy has provided insights (Bunker et al. 2011, Wang et al. 2003). Adhesion was usually correlated with the roughness of tablets and mitigated by lubrication (Toyoshima et al. 1988 Roberts et al. 2004, McDermott et al. 2011, Wang et al. 2015, Uchimoto et al. 2013). A KTP project involving punch manufacturer iHolland (I Holland 2014) identified adhesion mechanisms due to Van der Waals forces, capillary action, morphology (surface roughness), deformation mechanics of the granules, environment and the chemistry of the surfaces and developed a model for adhesion based on statistical data fitting.
The literature review above illustrates the complex nature of the problem of adhesion. Various hypotheses have been proposed and examined, however, a sufficient level of understanding of the underlying mechanisms has not yet been achieved.
Previous research at Leicester used characterization methods available in the Department of Engineering and proposed a classification of adhesion of Mannitol (a pharmaceutical excipient) to punch surfaces. This study led to identifying a new hypothesis which is proposed for PhD as follows.
Powder compaction involves mechanisms such as particle rearrangement, elastic deformation, followed by plastic deformation and/or breakage, which in turn lead to further rearrangement etc. Relevant to adhesion are the detailed processes occurring at the interface between particles and tooling, which is usually made of stainless steel. The interaction between particles and tooling requires consideration of friction and adhesion. Powder compaction involves dissipative processes that generate heat. At the interface heat is also generated due to friction. The hypothesis proposed involves considering the fully coupled thermo-mechanical behavior between powder and tooling leading to changes of material and surface properties and gradual deposition of the material.
The methodology involves experimental characterization of material properties and surfaces using nano-indentation and atomic force microscopy, respectively. This provides characterization of physical and mechanical properties of the particles. Thermo-mechanical analysis will be carried out to obtain conductivity and heat capacity. The existing friction measurements systems in the department will be modified to accommodate sub-millimeter sized particles. The data collected for materials prone to adhere to metal surfaces will be used as input for numerical analysis using continuum mechanics and finite element analysis.
For UK Students: Fully funded College of Science and Engineering studentship available, 3 year duration.
For EU Students: Fully funded College of Science and Engineering studentship available, 3 year duration
For International (Non-EU) Students: Stipend and Home/EU level fee waiver available, 3 years duration. International students will need to provide additional funds for remainder of tuition fees.
Please direct informal enquiries to the project supervisor.
If you wish to apply formally, please do so via: https://www2.le.ac.uk/colleges/scieng/research/pgr and selecting the project from the list.
Bakar et al, 2007. Powder Technology, 176, 137-147.
Bunker et al 2011. Drug Development and Industrial Pharmacy, 1–11.
I Holland Limited, 2014. Pharmatech. September 23.
McDermott et al, 2011. Powder Technology, 212(1), 240-252.
Mullarney et al, 2012. Pharmaceutical Technology, 36(1), 57-62.
Reed et al, 2015. Powder Technology, 285, 103-109.
Roberts et al 2004. Journal of Pharmacy and Pharmacology, 56(3), 299-305.
Simmons et al, 2012. Drug Development and Industrial Pharmacy, 38(9), 1054–1060.
Toyoshima et al, 1988. International Journal of Pharmaceutics, 46, 211-215.
Waimer et al, 1999 Pharmaceutical Development and Technology, 4(3), 359-367.
Wang et al, 2004. Journal of Pharmaceutical Sciences, 93 (2), 407-417.
Wang et al 2003. Journal of Pharmaceutical Sciences, 92(4), 798-814.