Browsing by Author "Närvänen, Tero"

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  • Närvänen, Tero (Helsingin yliopisto, 2009)
    Fluid bed granulation (FBG) is a widely used process in pharmaceutical industry to improve the powder properties for tableting. During the granulation, primary particles are attached to each other and granules are formed. Since the physical characteristics (e.g. size) of the granules have a significant influence on the tableting process and hence on the end product quality, process understanding and control of the FBG process are of great importance. Process understanding can be created by exploiting the design of experiment studies in well instrumented FBG environment. In addition to the traditional process measurements and off-line analytics, modern process analytical technology (PAT) tools enable more relevant real-time process data acquisition during the FBG. The aim of this thesis was to study different particle size measurement techniques and PAT tools during the FBG in order to get a better insight into the granulation process and to evaluate possibilities for real-time particle size monitoring and control. Laser diffraction, spatial filtering technique (SFT), sieve analysis and new image analysis method (SAY-3D) were used as particle size determination techniques. In addition to the off-line measurement, SFT was also applied in-line and at-line, whereas SAY-3D was applied on-line. Modelling of the final particle size and the prediction of the particle size growth during the FBG was also tested using partial least squares (PLS). SFT studies revealed different process phenomena that could also be explained by the process measurement data. E.g., fine particles entrapment into the filter bags, blocking of the distributor plate and segregation in FBG were observed. The developed on-line cuvette enabled SAY-3D image acquisition and visual monitoring throughout the granulations and it performed well even in very wet conditions. Predictive PLS models for the final particle size could be constructed. Based on this information, pulsing of the granulation liquid feed was presented as a controlling tool to compensate for the excessive moisture content during the FBG. A new concept of utilising the process measurement data to predict particle size during FBG was also successfully developed. It was concluded that the new methods and PAT tools introduced and studied will enable enhanced process understanding and control of FBG process.