Melt Granulation in Fluidised Bed: Screening of the Process Variables by Factorial Design

In recent years, the interest in melt granulation has increased due to the advantages of this technique respect to traditional wet granulation; utilizable equipments for melt granulation are high-shear mixer and fluidised bed [1]. The aim of the study was to evaluate, by asymmetrical factorial design [2], the contribution of some variables on the in situ melt granulation process performed in fluidised bed in order to identify the critical parameters that influence the granule properties and the process. The experiments have been performed in a lab scale apparatus (Mini-Glatt), employing spray dried lactose monohydrate as filler. Six factors were studied at different levels: the binder type was evaluated at 2 levels (Lutrol F68 and Lutrol F127), while the percentage of the binder, the size of the binder particles, the inlet air temperature, the inlet air rate and the granulation time were studied at 3 levels. The 16 experiments were run randomly in duplicate. Five variables were selected as experimental responses: the total process time, the yield, the particle size (d50), the friability and the flowability of the produced granules. The analysis of the results showed that the percentage of the binder, the inlet air temperature and the inlet air rate significantly influenced all the experimental responses, while the binder type, the size of the binder and the granulation time had minor “weight” on the entire process. Five additional tests allowed to assess the validity of the screening. In conclusion the factorial design results permitted to identify the most important variables of the in situ melt granulation process in fluidised bed. These findings result crucial for the ongoing further optimisation phase of the process.