Monitoring Granulation Rate Processes Using Three PAT Tools in a Pilot-Scale Fluidized Bed

Abstract

Abstract. The purpose of this research was to analyze and compare the responses of three Process Analytical Technology (PAT) techniques applied simultaneously to monitor a pilot-scale fluidized bed granulation process. Real-time measurements using focused beam reflectance measurement (Lasentec FBRM) and near-infra red spectroscopy (Bruker NIR) were taken by inserting in-line probes into the fluidized bed. Non-intrusive acoustic emission measurements (Physical Acoustic AE) were performed by attaching piezoelectric sensors on the external wall of the fluidized bed. Powder samples were collected at regular intervals during the granulation process and characterized offline using laser diffraction, scanning electron microscopy, stereo-optical microscopy and loss on drying method. PAT data comprising chord length distribution and chord count (from FBRM), absorption spectra (from NIR) and average signal levels and counts (from AE) were compared with the particle properties measured using offline samples. All three PAT techniques were able to detect the three granulation regimes or rate processes (wetting and nucleation, consolidation and growth, breakage) to varying degrees of sensitivity. Being dependent on optical signals, the sensitivities of the FBRM and NIR techniques were susceptible to fouling on probe windows. The AE technique was sensitive to background fluidizing air flows and external interferences. The sensitivity, strengths and weaknesses of the PAT techniques examined may facilitate the selection of suitable PAT tools for process development and scale-up studies.

Evaluation of in-line spatial filter velocimetry as PAT monitoring tool for particle growth during fluid bed granulation

“…The use of on-line image analysis for granule size determination was initiated by Watano et al [4][5][6][7][8][9] and more recently investigated by Naervanen et al [10]. As a near infrared (NIR) spectrum is dependent on the chemical and physical composition and properties of a measured sample, NIR has been extensively investigated for the fast and non-destructive (at-line, online or in-line) particle size monitoring during granulation, usually combined with moisture content determination [11][12][13][14][15][16]. A couple of reports can be found on the application of focused beam reflectance measurements (FBRM) in-line or at-line during fluid bed granulation [15,17].…”

“…As a near infrared (NIR) spectrum is dependent on the chemical and physical composition and properties of a measured sample, NIR has been extensively investigated for the fast and non-destructive (at-line, online or in-line) particle size monitoring during granulation, usually combined with moisture content determination [11][12][13][14][15][16]. A couple of reports can be found on the application of focused beam reflectance measurements (FBRM) in-line or at-line during fluid bed granulation [15,17]. Tok et al describe the combined use of FBRM, NIRS and acoustic emission measurements in a pilot-scale fluidized bed granulation process [15].…”

“…A couple of reports can be found on the application of focused beam reflectance measurements (FBRM) in-line or at-line during fluid bed granulation [15,17]. Tok et al describe the combined use of FBRM, NIRS and acoustic emission measurements in a pilot-scale fluidized bed granulation process [15]. In-line FBRM and NIRS probes were able to detect the three granulation rate processes to varying degrees of sensitivity due to fouling.…”

Texture analysis as a tool to study the kinetics of wet agglomeration processes

“…Techniques such as the focused beam reflectance measurement (FBRM), which allows to follow the granule chord length evolution in real time (Huang et al 2010), are starting to be used in wet granulation studies. Also the simultaneous combination of different techniques such as FBRM, acoustic emission measurement and near infrared spectroscopy have been used to asses granulation rates in fluidized beds (Tok et al, 2008). A direct measurement and control of granule growth can be also achieved through the use of sensors capturing digital images of the powder bed and analyzing them with image analysis techniques.…”

Batch statistical process control of a fluid bed granulation process using in-line spatial filter velocimetry and product temperature measurements

“…Hence, the change in PSD during granulation gives a direct indication of the batch progress and batch quality. Several techniques have been evaluated to monitor PSD during granulation in real-time: near infrared spectroscopy (Alcala et al, 2010;Findlay et al, 2005;Frake et al, 1997;Goebel and Steffens, 1998;Kaddour and Cuq, 2009;Luukkonen et al, 2008;Tok et al, 2008), focused beam reflectance method (Hu et al, 2008;Huang et al, 2010;Tok et al, 2008), spatial filter velocimetry (SFV) (Burggraeve et al, 2010;Lipsanen et al, 2008;Narvanen et al, 2008Narvanen et al, , 2009), image analysis (Laitinen et al, 2004;Naervanen et al, 2008;Watano and Miyanami, 1995;Watano et al 1996Watano et al , 1997Watano et al , 2000Watano et al , 2001Watano, 2001) and acoustic emission monitoring (AE) (Gamble et al, 2009;Halstensen et al, 2006;Matero et al, 2009;Tok et al, 2008;Whitaker et al, 2000). Each technique has its own advantages and shortcomings.…”