Granule breakage during drying processes

The drying of wet granules often involves an unwanted and uncontrolled size reduction. Current FDA PAT guidance stresses importance of process control and understanding. The aim of this study is to determine and understand the breakage phenomena during drying processes in order to control these processes. High shear granulated lactose granules with water as binding liquid were dried during variable periods. Subsequently the (partially) dried granules were exposed to agitation by the impeller and chopper in the granulator. Granule characterization revealed that the change in granule size of (partially) dried granules is dependent on-water content and follows a three phase system characterized by a growth, plateau and breakage phase. The derived yield stress of the granules is a function of velocity. From this it is concluded that in the plateau phase above minimum water content, stress behavior of granules can be described with Rumpfs' dynamic granule strength, whereas below minimum water content (breakage phase) granule strength is determined by the solid bridges. The extent and velocity of stress and water content of the granules during the process determine the size reduction phenomena. (c) 2006 Elsevier B.V. All rights reserved

Granule characterization during fluid bed drying by development of a near infrared method to determine water content and median granule size

Purpose. Water content and granule size are recognized as critical process and product quality parameters during drying. The purpose of this study was to enlighten the granule behavior during fluid bed drying by monitoring the major events i.e. changes in water content and granule size. Methods. NIR spectra collected during drying and water content of sampled granules were correlated by principal component analysis (PCA) and partial least squares regression (PLSR). NIR spectra of dried granules were correlated to median granule size in a second PCA and PLSR. Results. The NIR water model discriminates between various stages in fluid-bed drying. The water content can be continuously predicted with errors comparable to the reference method. The four PLS factors of the granule size model are related to primary particle size of lactose, median granule size exceeding primary particle size and amorphous content of granules. The small prediction errors enable size discrimination between fines and granules. Conclusion. For product quality reasons, discrimination between drying stages and end-point monitoring is highly important. Together with the possibilities to determine median granule size and to distinguish fines this approach provides a tool to design an optimal drying process