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Correlation between Wet Granulation Kinetic Parameters and Tablet Characteristics

Withoon Kornchankul a, Neil H. Parikh b, and Adel Sakr c

Chelsea Laboratories, Inc.a, Cincinnati, Ohio, Watson Pharmaceuticals, Inc.b, Corona, California, and Industrial Pharmacy Graduate Program, University of Cincinnati Medical Center c, Cincinnati, Ohio (USA)

The aim of this study was to investigate the feasibility to correlate wet granulation parameters with tablet characteristics and to use torque measurement to control the end point of wet granulation process of both microcrystalline cellulose and lactose in high-shear mixer at various impeller speeds, wet mixing time, granulating fluid amount, and binder concentration. Both matrices were separately granulated in an instrumented high-shear mixer using water as aqueous granulating fluid. A modified central composite designed study was performed to investigate the influence of binder concentration (0 to 10 % w/w), the granulation fluid amount (depending on matrices), wet mixing time (0 to 1 min), and impeller speed (261 and 522 rpm) on the tablet characteristics. During granulation, torque was measured and a torque profile was generated. The parameters obtained from the profile were correlated with the corresponding tablet characteristics. The scatter plots of hardness data indicate that, in microcrystalline cellulose module, tablet hardness is higher than 7 kp a s long as end torque is less than 100 lb-in, granulation rate is less than 0.4 lb-in/s, and granulation extent is less than 13 000 lb-in · s . Strong correlation was found and could be potentially used to determine a specification of granulation for tablet production. This study showed that the granulation process can be controlled by means of the torque measurement through the concept of wet granulation kinetics.

Key words High-shear mixer · Lactose · Microcrystalline cellulose · Tablets · Wet granulation