Granulation End-Point Determination

In the direct measurements, the physicochemical properties of the powder mixture are monitored during the wet-granulation process. These properties could be mass conductivity and granule size. 

In the indirect measurement, both electrical and mechanical characteristics of the motor are monitored to control the granulation end point. The electrical characteristics of the motor are motor cmrent and power consumption. The mechanical characteristics of the motor are torque and tachometry. 

The drawback of monitoring power consumption is that the signal is affected by a number of factors, such as product (formulation), equipment, or process variables. For example, the densification properties of the starting materials, type and amount of binder used, addition rate of binder solution, impeller speed, etc., influence the power consumption profile. Wear and tear of the granulator could also affect the power consumption signal. Thus, the power consumption profile for a granulation process is formulation and process specific. 

The end-point control of granulation by power consumption measurement in a 25 L high-shear mixer was investigated by Holm et al. (42). The effect of impeller design, impeller speed, liquid addition rate, type of binder, and mixing ratios between lactose and starch on the correlation between power consumption and granule 

An alternative to power consumption is torque measurement. A high-shear mixer was instrumented with a new capacitive sensor, a watt meter, and a strain-gauge torque sensor (50). Placebo formulations containing DCP, MCC 101, MCC 102, and lactose were granulated in the high-shear granulator. A similar map (profile of torque measurement or power consumption) of the granulation process was obtained for power consumption and torque measurement. 

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Levin M. 2006. Wet granulation end-point determination and scale-up. In Encyclopedia of pharmaceutical technology. New York Marcel Dekker 4078-4098. 

Several attempts were made to evaluate the use of FBRM particle size analyzer as a potential tool for granulation end-point determination. Dilworth et al.f have compared power consumption, FBRM, and acoustic signals in a study of a wet granulation process in Fielder PMA 200 mixer. It was found that these techniques were complimentary, with FBRM probe capable to follow median granule size growth even when the power consumption curve showed a plateau. 

Wet Granulation End-Point Determination and Scale-Up Batch No. JJ0214A... 

The Leuenberger s ideas relating to the use of power consumption for wet granulation end-point determination were tested and implemented by numerous researchers.P " " " ... 

Farber L, Tardos GI, Michaels JN. Evolution and structure of diying material bridges of pharmaceutical excipients studies (Hi a mUnoscofnc slide. Chem Eng Sci 2003 58 (4515-25). Levin M. Wet granulation End-point determination and scale-up. Encyclopedia of niarmaceutical Technology. Third Edition 2006, J. Swarbrick, Ed. Boca Raton, FL Taylor Francis. 

High-shear granulation has been one of the most commonly used methods to produce granules since the early 1980s (4). Hence, this chapter discusses in detail, the equipment, process variables, formulation requirements, granulation end-point determination, and scale-up considerations of the high-shear granulation process. 

Reduction of process dust, thus minimizing exposure to workers Obtaining predictable granulation end-point determination. 

During scale-up, after selecting the granulator with matching Froude number and similarly shaped impeller blades, the granulation end point can be determined by any one of the techniques described earlier. A new approach for scale-up based on the use of power consumption, as the granulation end-point determination, is shown below. 

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