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 microm) is nearly four times that of the largest fraction (300-425 microm). These results show that size reduction can be an effective strategy to address the problem of over-granulation.
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Limin
L
Shi
Yushi
Y
Feng
Changquan Calvin
CC
Sun
D002482:Cellulose; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D005079:Excipients; D010316:Particle Size; D011208:Powders / Q000737:chemistry*; D013607:Tablets; D013718:Tensile Strength
D005079:Excipients; D011208:Powders; D013607:Tablets; D002482:Cellulose; C109691:microcrystalline cellulose