Roles of Granule Size in Over-Granulation During High Shear Wet Granulation

A mechanistic understanding of the over-granulation problem during high shear wet granulation (HSWG) process can guide efficient development of robust formulation and manufacturing process. Using microcrystalline cellulose (MCC) as a model compound, we demonstrate that size enlargement is an important mechanism for over-granulation in HSWG A higher granulation water level results in larger granules and lower tabletability. With increasing water, granules enlarge sharply when water level is higher than 65%. Granule tabletability deteriorates with increasing granule size and becomes over-granulated when more than 70% water is used. For a batch of over-granulated granule that is ground and sieved, tabletability of the sieved fractions decreases with increasing granule size. The tabletability of the finest fraction (45-90 mu m) is nearly four times that of the largest fraction (300-425 mu m) These results show that size reduction can he an effective strategy to address the problem of over-granulation (C) 2010 Wiley-Liss, Inc and the American Pharmacists Association J Pharm Sci 99 3322-3325, 2010