Studies on the fluidised bed granulation process.
This study is an evaluation of the process of fluidised bed granulation with the objectives of elucidating the mechanism of granule formation and identifying the fundamental parameters affecting granule quality thereby enabling the true benefits of the process to be realised. Initially the effect of seven process variables upon granule quality was quantified using a factorially designed experiment. During granule assessment the torque generated by a paddle revolving in a granule mass was shown to be a useful measure of granule quality. The variables found to exert a significant effect upon granule quality were those which affected the wetting of the powder mix and rate of evaporation during granulation. A closer examination of those factors influencing bed wettability was indicated. This was achieved by studying the spray characteristics and droplet size of the atomised granulating solution, and investigating powder bed hydrophobicity. Spray characteristics of the atomised granulating solution were measured using a Malvern ST 1800 Particle and Droplet Size Analyser. A direct correlation was shown between droplet size and granule siize. Coarse, free flowing granules were obtained from sprays with large droplets, wide droplet size distributions and high granulating solution addition rates. A linear relationship was shown between the cosine of the solid/liquid contact angle and granule size. The addition of surfactant {sodium lauryl sulphate} to a model hydrophobic system was shown to improve granulation. This was related to improved powder/liquid affinity. Surfactant dissolved in the granulating solution gave slightly coarser granules with improved flow properties than when added directly to the powder mix. This was attributed to changes in spray characteristics and improved wetting by the atomised granulating solution. The growth mechanism and granule structure were subsequently investigated in a number of model powder systems using sieve analysis, scanning electron microscopy, a specially developed fluorescent technique to monitor binder distribution and a solvent extraction procedure which left a network of binder. Close examination of the data enabled a growth mechanism to be proposed for lactose and modifications to this were discussed for the other materials investigated. Thus, based on the changes occurring in the microenvironment during powder particle/droplet collision, those factors which significantly influence granule formation have been identified. These were principally the physico-chemical properties of the starting materials and the properties of the granulating droplets.
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