(47a) Agglomerates - Structures and Their Dissolution Behaviour

A computer modelling approach to simulating dissolution behaviour of granular microstructures is presented. It is a hybrid of three mesoscale models, which provides a self-contained and extendable modelling framework to look at the relationship between granular microstructure the dissolution behaviour. The dissolution model is essentially a finite difference solver of the convection-diffusion equation with Noyes-Whitney equation being used as boundary conditions at solid/solvent interfaces. To provide structural input to the dissolution model, a digital particle packing algorithm, called DigiPac, which is capable of generating packing structures of particles of arbitrary shapes and sizes, is employed. Alternatively, X-ray microtomography can be used to obtain 3D structures of real granules. The flow model, needed to provide input for convection, is based on the Lattice Boltzmann Method. It is adopted mainly for its convenience of incorporating digitally specified 3D complex structures, as provided by both DigiPac and X-ray tomographic imaging. Dissolution in the context of drug release has been investigated over the years both experimentally and theoretically at testing apparatus level, where flow conditions have been the main focus, and at single particle level, where often a simple geometrical shape is assumed. The influence of complex microstructures on dissolution is, however, less extensively studied. Work reported here represents an attempt to make use of real or more realistic particle shapes. Our simulation results suggest that how fast particles in a given granular structure dissolve is more strongly influenced by their spatial arrangement within the granule than by the flow. Some benchmark tests are presented, which show that the model behaves as expected. Examples are given to demonstrate the theoretical capabilities of the hybrid model. The ultimate goal is to develop a computer software design aide for formulation development of drugs.