Binder liquid distribution during granulation process and its relationship to granule size distribution

The aim of this study is to characterize the impact of binder liquid distribution on granule properties during the wet granulation process. A new parameter, namely the binder liquid transfer coefficient, is used to characterize binder liquid distribution. The relationships between binder liquid distribution coefficient and granule size distribution are discussed. Granules are made of lactose alpha-monohydrate (97.5% w/w, d₅₀ = 31 μm) and polyvinylpyrrolidone (2.5% w/w, d₅₀ = 89 μm) and are manufactured in a Mi-Pro high shear mixer (Pro-C-epT, Belgium). Nigrosine is incorporated as a tracer in the binder liquid in order to detect its distribution in the granules during the process. The results show that the binder liquid is heterogeneously distributed at the beginning of the process whereas it tends to be evenly distributed in the powder during the process. The binder liquid transfer in granule classes obeys a first-order law and the binder liquid transfer coefficient appears to be related to operating conditions: high rotation speed, low liquid flow rate and low liquid viscosity favour the achievement of high liquid transfer coefficient. In addition, the higher the coefficient, the earlier the homogenization and the wider the granule mean diameters. Thus, granule size distribution can be controlled by the binder liquid distribution process. A binder liquid distribution mechanism is proposed, which makes it possible to discuss the influence of the operating parameters on the granule construction process.