Nucleation and binder dispersion in wet granulation

The primary objective of this thesis was to develop a nucleation regime map to determine the controlling nucleation mechanism as a function of material properties and operating parameters. Two distinct regimes of nucleation were identified. The drop controlled nucleation regime occurs when nucleation conditions are ideal and one drop produces one nucleus granule and the controlling property is the droplet size. The nuclei formation kinetics are fast and the binder droplets penetrate into the powder bed pores almost immediately. In this region, the nuclei distribution reflects the drop size distribution as one drop tends to form one granule provided that (a) drops hitting the powder surface do not overlap - low spray flux Ya and (b) the drop must wet into the bed completely before bed mixing brings it into contact with another partially absorbed drop on the bed surface - low penetration time tp. If either criterion is not met, powder mixing characteristics will dominate. In the mechanical dispersion regime, the viscous or poorly wetting binder is slow to flow through the powder pores and form nuclei and good mixing is required for binder dispersion. The kinetics of nuclei formation were characterised using a simple drop penetration time test. A single drop of binder fluid was placed on a loosely packed powder bed and the time taken for the fluid to penetrate completely was measured for a range of powder and binder combinations. Loosely packed powder beds contain large macrovoids which are included in the existing Kozeny approach to estimating pore size. However it was found that these pores do not participate in liquid flow. A new two phase model was proposed where the total volume of the macrovoids was assumed to be the difference between the bed porosity and the tap porosity. A new parameter, the effective porosity eeff, was defined as the tap porosity multiplied by the estimated fraction of pores that terminate at a macrovoid and are effectively blocked pores. The pore sizes and drop penetration times were recalculated using the effective porosity and the predicted tp values were generally within an order of magnitude of the experimental results for all powders. The drop penetration time is reduced by small drops, low viscosity fluids, porous powders (but without macrovoids), large powder pores, high surface tension, low contact angle and pre-wetting of the powder bed. A new dimensionless group, the dimensionless spray flux Ya was defined to characterise the three most important operating variables in binder dispersion: liquid binder flowrate, drop size and powder flux through the spray zone. At low Ya, the majority of drops land on the powder sufficiently well separated to allow ideal drop controlled nucleation where one drop forms one granule. As Ya increases, the probability of drop footprints overlapping to give larger agglomerate nuclei increases. Monte-Carlo simulations were performed to validate the spray flux theory. The proportion of nuclei formed from single drops falls exponentially as Ya increases and to remain in the drop controlled regime Ya must be kept below 0.1. Analytical solutions based on the Poisson distribution for the fraction of single drop nuclei as a function of Ya were an excellent match with the Monte-Carlo data. Further validation experiments in carefully designed ex-granulator experiments and in an industrial granulator were performed. The results matched the theoretical solutions and demonstrated the ability of Ya to describe the nucleation zone in a real granulator. The proposed nucleation regime map demonstrated the interaction between drop penetration time and spray flux in nucleation. At short penetration times, such as the water and lactose system, decreasing Ya causes a shift towards the drop controlled regime and a narrower nuclei distribution. When penetration time is long, the nuclei size distribution is always larger and broader. Granulation may still be successful if the mechanical dispersion forces are able to break up the binder clumps and distribute the binder through the powder. The nucleation regime map should prove to be a useful tool for maintaining effective liquid distribution during scale-up as well as a useful trouble-shooting tool. It allows the dominant mechanism controlling the nucleation process to be easily identified using relatively simple parameters and a rational approach can then be used to control the properties of the nuclei