Spherical agglomeration is a size enlargement technique which is highly suited to high value products with problematic morphologies. The addition of a partially immiscible bridging liquid to a suspension allows the formation of dense, spherical agglomerates with superior properties, i.e. flowability and compressibility. These products reduce further downstream processing requirements, and thus, the associated energy, time, and cost.
Currently, the mechanistic understanding of the process is limited, and few studies specifically investigate and elucidate these mechanisms to further a wider understanding as a whole. Conversely, the current literature provides a detailed account of the influence of process and formulation parameters on the final agglomerate properties. One such parameter is the bridging liquid-solid ratio, of which an optimal range can be found. Within the range, superior agglomerates are formed. However, these are specific and change for each system under consideration, due to failure to account for bridging liquid miscibility.
To address this, a new parameter is defined – the true bridging liquid-solid ratio (TBSR), which is defined as the volume of the bridging liquid rich phase divided by the volume of solid product. To evaluate miscibility between the bridging liquid and solvent, a ternary phase diagram is required. Here the phase diagram is determined through a novel combined approach using both experimental and computational studies. Analysis of these diagrams and computation allows the volume of the bridging liquid-rich phase to be calculated. This dimensionless parameter allows easy comparison across a variety of systems. The new definition has been partially validated through a rigorous experimental plan. The extent of agglomeration, and agglomerate size distribution is measured for salicylic acid (crystals) in several acetone-water solvent systems with three different bridging liquids at a solids loading of 3%. The results showed much closer alignment between the agglomerate profiles across different systems when TBSR is used to measure the required amount of bridging liquid.
A kinetic study of spherical agglomeration of paracetamol using immersion nucleation was performed. An optimal TBSR range of 0.7 – 0.8 was found. Five distinct operational zones were found: Zone A, insufficient bridging liquid for complete agglomeration; Zone B and C, high quality, well controlled agglomerates were formed; Zone D and E, poorer quality agglomerates were formed and the time to paste was short. These zones were found to be independent of the solid loading used. Experimental results were compared to a previously developed mathematical model, which correctly predicts the experimental trends. The model predicts results which are quantitatively very different in timescale, compared to experimental observations.
