Formation of hollow core granules by fluid bed in situ melt granulation: modelling and experiments.

Granules with a characteristic core-shell internal structure have been formed by in situ melt fluid-bed granulation, using d-mannitol primary solid particles and poly-ethylene glycol (PEG-6000) binder. The effect of binder particle size and binder/solids ratio on granule size distribution was systematically investigated. The mean granule size was found to be directly proportional to the binder particle size. The binder amount did not measurably affect the granule size, only the fraction of un-granulated fines. The microstructure of the granules was analysed by X-ray micro-tomography; the average shell thickness in the granules was found to depend on the binder/solids ratio, and the core volume was found to be directly proportional to the binder particle size. However, for binder particle size below a certain value the core-shell structure disappeared. A mathematical model based on a layering growth mechanism has been proposed and found to be consistent with experimental data. The proposed growth mechanism was confirmed by creating granules with bi-modal size distribution using a mixture of differently sized binder seeds.