Rheology, granule growth and granule strength: Application to the wet granulation of lactose-MCC mixtures

This study aims at better understanding the wet granulation process of a binary mixture composed of microcrystalline cellulose (water insoluble) and lactose (water soluble). It investigates the effect of formulation (proportion of the different components in the mixture) on the granule growth kinetics, the evolution of granule morphology during granulation, the wet mass consistency and dry granule strength of the end product. Additionally the influence of mixer design has been studied by up scaling the process from the 1.9 L Mi-pro high shear mixer used as the reference scale to a 6 L Diosna P1-6 high shear mixer. The scale-up rules investigated were constant impeller tip speed and constant Froude number. Our results allowed us to draw the following conclusions:

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The increase in MCC content is found to increase the optimum binder requirement for granulation, wet mass consistency and dry granule strength.

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Granule growth takes place in three distinct stages: wetting, nucleation and growth. These stages can be identified with the help of the recorded torque values during the granulation process or by the evolution of granule size and granule morphology.

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The characterization of the starting materials by moisture sorption isotherms brings more insight to the role of each component during the granulation process.

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The increase of the granulation scale has little influence on the observed growth mechanism. However bi-modality of the granule size distribution is increased, wet mass consistency and dry granule strength are decreased with increasing scale of operation.