Next generation fluidized bed granulator automation

Abstract

A system for fluidized bed granulator automation with in-line multichannel near infrared (NIR) moisture measurement and a unique air flow rate measurement design was assembled, and the information gained was investigated. The multivariate process data collected was analyzed using principal component analysis (PCA). The test materials (theophylline and microcrystalline cellulose) were granulated and the calibration behavior of the multichannel NIR set-up was evaluated against full Fourier Transform (FT) NIR spectra. Accurate and reliable process air flow rate measurement proved critical in controlling the granulation process. The process data describing the state of the process was projected in two dimensions, and the information from various trend charts was outlined simultaneously. The absorbence of test material at correction wavelengths (NIR region) and the nature of material-water interactions affected the detected in-line NIR water signal. This resulted in different calibration models for the test materials. Development of process analytical methods together with new data visualization algorithms creates new tools for in-process control of the fluidized bed granulation.

Particle Size, Moisture, and Fluidization Variations Described by Indirect In-line Physical Measurements of Fluid Bed Granulation

“…The inlet air humidity of the process air was modified with a humidifying system (Defensor Mk4; Brautek Oy, Espoo, Finland) (19). The parameters measured and derived are found in Table I and the instrumentation is described in further detail in Rantanen et al (7). The atomization pressure of the granulating liquid was 0.1 MPa and nozzle height was set to 45 cm from the distributor plate.…”

“…The fluidization process allows automatically controlled operations and fluid bed granulators are becoming increasingly instrumented including indirect physical measurements, e.g. temperatures, flow rates, and pressure differences (5)(6)(7)(8)(9). Until recently, these measurements have mainly been utilized for monitoring purposes and not for finding critical interactions or variation sources of the processes.…”

Process analytical technology (PAT) approach to the formulation of thermosensitive protein-loaded pellets: Multi-point monitoring of temperature in a high-shear pelletization

“…Although a few authors have demonstrated the use of multivariate near infrared (NIR) chemometric models coupled with temperature and humidity data to develop models for better understanding the granulation and coating process (Rantanen et al, 2000;Rantanen et al, 2001), the use of PyroButton-TH® (made by Opulus Ltd.) calibrated sensors (ISO 17025) for high-shear pelletization was never explored. These data loggers were reported for use in sterilization validation and monitoring in steam sterilization, humidity and temperature monitoring of environment and facilities such as warehouse, and processing procedures in pharmaceutical technology (Pandey et al, 2014a(Pandey et al, , 2014bKestur et al, 2014;Macchi et al, 2016).…”

Moisture content determination of pharmaceutical pellets by near infrared spectroscopy: Method development and validation

“…Indeed, the NIR spectrum of water contains two major absorption bands at 5155 cm −1 and 6895 cm −1 making this technique selective enough to allow a sensitive determination of moisture content [3]. NIR spectroscopy has already been used in different fields such as the pharmaceutical [13][14][15][16][17][18], the food [19] and the fuel industry [20] to determine moisture content. In the pharmaceutical field, Rantanen et al [18] described the in-line drying monitoring of a pellet formulation.…”