End point determination for wet granulation in high shear mixers

Jingying Ye, Purdue University

Abstract

The purpose of the first part of the study was to determine the end point for granulations with continuous binder addition by evaluating granule properties. The amperage curve was used to monitor the agglomeration process. The strength and the size distribution of dry granules were measured at various time points. It was found that the weight percentage of granules within the size range from 16 to 100 mesh first increased, reached steady state and then decreased significantly as the granulation time increased. On the other hand, after an initial steady increase, the granule strength increased sharply. The sharp increase of granule strength associated with the decrease of the granule weight percentage, were accompanied in most cases by the onset of high frequency fluctuations in the amperage curve, indicating the formation of large and hard granules. PLS model was also tried in this study to analyze the relationship between process variables and granule properties. In the second part of the study, homogeneity and granulation density of a wet granulation were monitored as a function of massing time in a high shear granulator, using a dielectric sensor. After the initial addition of binder, granulation was stopped at various time points during wet massing for dielectric measurements. The dielectric signals measured at different locations inside the mixer indicated that, in most cases, water distribution appears to become uniform after 10 minutes. It was also found that the granulation density derived from the dielectric signal first increased, reached a relatively steady state after 10 minutes, and then increased significantly after 16 minutes. The combined information of granulation density and moisture distribution indicated an end point time window in a range of 10–14 min, which was supported by the information of wet granule size obtained from cryogenic sieving. It was suggested that the dielectric sensor could be used to determine the granulation end point by stopping the granulation briefly at various time points during wet massing.

Degree

Ph.D.

Advisors

Kildsig, Purdue University.

Subject Area

Pharmacology|Pharmaceuticals

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