James Elliott
Department of Materials Science and Metallurgy, University of Cambridge, Pembroke Street, Cambridge, CB2 3QZ, United Kingdom
The optimisation of solid dosage form (i.e. tablet) performance is crucially dependent on a detailed understanding of the relationship between the size, shape and mechanical properties of the constituent powders and the characteristics of the final compact. In this lecture, I will describe a programme of work undertaken in Cambridge over the last decade studying the relationship between the size, shape and mechanical properties of the constituent powders and the characteristics of the final compact. The approach is to use a combination of experimental compaction simulation and discrete element models to parameterise appropriate constitutive equations (e.g. the density-dependent Drucker-Prager cap model[1]) for the powders, which can then be used in finite element simulations of the tablet compaction process. The discrete element models incorporate well-defined elastic module and contact force models, including friction to couple the rotational and translational degrees of freedom of the particles.[2] The framework can be extended to model frangible granules of arbitrary shape undergoing uniaxial or triaxial compression and simple shear. The finite element simulations encompass process parameters, such as punch shape, die geometry and compaction speed.[3,4] The overall aim is to link the molecular scale properties of the constituents to the mesoscale powder properties, and ultimately to predict the stress and density distributions in the final compact. This modelling work is validated by studies of generic APIs (paracetamol and acetazolamide) and excipients (microcrystalline cellulose and lactose) using compaction simulators and novel imaging techniques, such as X-ray tomography and strain-mapping using small-angle X-ray scattering. Understanding such compaction behaviour may be relevant to predicting performance of tablets with embossed features or compacted artefacts of more complex shape.
[1] Han, L.H., Elliott, J.A., Bentham, A.C., Mills, A., Amidon, G. and Hancock, B.C. , Int. J. Solids Struct., 45, 3088-3106 (2008).
[2] Fu, X., Dutt, M., Bentham, A.C., Hancock, B.C., Cameron, R.E. and Elliott, J.A., Powder Tech., 167, 134-140 (2006).
[3] Wu, C.-Y., Ruddy, O.M., Bentham, A.C., Hancock, B.C., Best S.M. and Elliott, J.A. “Modelling the mechanical behaviour of powders during compaction”, Powder Technology, 152, 107-117 (2005); Wu, C.-Y., Hancock, B.C., Mills, A., Bentham, A.C., Best S.M. and Elliott, J.A. “Numerical and experimental investigation of capping mechanisms during pharmaceutical tablet compaction”, Powder Technology, 181, 121-129, (2008).