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

• Published in: Journal of pharmaceutical sciences Vol. 99; no. 8; pp. 3322 - 3325
• Main Authors: Shi, Limin, Feng, Yushi, Sun, Changquan Calvin
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.08.2010; Wiley Subscription Services, Inc., A Wiley Company; Wiley; American Pharmaceutical Association
• Subjects: Biological and medical sciences; Cellulose; Chemistry, Pharmaceutical; Drug Compounding; Excipients; General pharmacology; granule size; high shear wet granulation; Medical sciences; microcrystalline cellulose; over-granulation; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Powders - chemistry; Tablets; Tensile Strength; microcrystalline cellulose; over-granulation; granule size; high shear wet granulation; Microcrystalline material; Wet granulation; Shear; Pharmaceutical technology; Cellulose; Granule
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.22118

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 (45–90μm) is nearly four times that of the largest fraction (300–425μm). These results show that size reduction can be an effective strategy to address the problem of over-granulation.