End-point detection in a wet granulation process.
The purpose of the experiments in this paper was to evaluate granulation end-point control by power consumption measurement in a 25-L high shear mixer. The effect of impeller design, impeller speed, liquid addition rate, type of binder, and mixing ratio between lactose and starch on the correlation between power consumption and granule growth was investigated in the liquid addition phase of the process using a fractional factorial experimental design. There was found generally a linear correlation between power consumption and mean granule size, but this correlation was dependent on the impeller design, the impeller speed, and the type of binder. However, an end-point control based on power consumption was not found to be sensitive to variations in the lactose:starch ratio. It was concluded that it was possible to control the liquid addition by the level detection method by which the liquid addition is stopped at a predetermined level of power consumption. An end-point control based upon the peak detection method was not generally applicable, because a peak in the differentiated power consumption signal could not be identified in all the experiments.
Holm
P
P
Pharmaceutical Development, H. Lundbeck A/S Ottiliavej 9, 2500 Valby, Denmark. ph@lundbeck.com
Schaefer
T
T
Larsen
C
C
D013213:Starch; D013607:Tablets; D013678:Technology, Pharmaceutical
D013607:Tablets; D013213:Starch