Qualitative proof of liquid dispersion and penetration-involved granule formation in a high shear mixer

The origination of granules in the early seconds is an important aspect of high shear granulation. To elucidate these mechanisms, a substandard amount (1.5% w/w) of an aqueous hydroxypropyl cellulose solution was added to four different lactose mixtures: (1) lactose 100 M (d(4,3) approximately 170 microm), (2) lactose 200 M (d(4,3) approximately 50 microm), and (3, 4) 10% magnesium stearate/lactose 100 or 200 M. Between 1 and 15 s after binder addition samples were taken, which were immediately frozen in liquid nitrogen. The frozen sample was sieved into granular (> 280 microm) and non-granular-material (< 280 microm). The binder distribution in these fractions was determined. The observed binder distribution behaviour revealed that three different nucleation mechanisms can occur: (I) For lactose 100 M holds that all the binder is initially located in the granules. These granules are subsequently broken again. (II) The lactose 200 M granules also contain 100% of the added binder liquid. Contrary to lactose 100 M the lactose 200 M granules remain intact during the process. It is argued that in both cases liquid penetration is responsible for the accumulation of all liquid in the granules. A theoretical evaluation also confirmed that liquid penetration leads to the formation of the primary granules (III) No liquid penetration is possible in the hydrophobic magnesium stearate/lactose mixtures and the binder is completely dispersed in the non-granular material.