Low shear granulation of pharmaceutical powders: Effect of formulation on granulation and tablet properties

Low shear granulation, which is a form of wet granulation, is an important unit operation in the pharmaceutical, detergent and food industries. The granulation mechanisms for wet granulation include wetting and nucleation, consolidation and growth and attrition and breakage. In an experimental study the influence of process parameters on the low shear granulation was investigated using lactose and starch as model pharmaceutical powders and CMC solution as a model binder. Four parameters: binder viscosity; binder content; ratio of starch to lactose; and shear rate, were investigated at granulation times of 1 and 12 min using a factorial design technique. The data indicated that increased mass mean diameter and was found using higher viscosity binders and high liquid-solid ratio. In general, lower mass mean diameters were found at longer granulation times, which may suggest that granule breakage has a significant influence on this particular low shear agglomeration process. Moreover, three different size ranges of granules taken from the low shear granulation processes under various processing conditions were subsequently pressed into tablets using tablet press. Standard pharmaceutical hardness and disintegration analyses were performed on the tablets. These analyses indicated that the formulation (i.e., starch–lactose and liquid–solid ratios) rather than granulation process parameters had a stronger influence on the mechanical properties of the tablets.