Focused beam reflectance measurement

Figure 1. Focused Beam Reflectance Measurement (FBRM ) data after DBX-1 crystallization.

Sensors for particle size characterization used for crystallization include ultrasound attenuation measurement/ " laser diffraction/ and laser backscatteiing/ commercially called focused beam reflectance measurement (FBRM). Ultrasonic attenuation spectroscopy has been used to monitor the crystallization process parameters such as the crystal size distribution, concentration, and the onset of nucleation during batch crystallization of L-glutamic acid/ Off-line laser diffraction has been used to measure the crystal size distribution in the development of the crystallization process for a pharmaceutical intermediate/ ... 

Ganguly, S. Gao, J.Z. Application of On-line Focused Beam Reflectance Measurement Technology in High... 

With the advancement of online measurement techniques such as focused beam reflectance measurement (FBRM) and Fourier transform infrared (FTIR), it is now possible to obtain particle size distribution and solution concentration information rapidly through these in-situ probes. In one experiment, hundreds of data points can be generated. With proper experiment design, the model-based experimental design for crystallization is capable of obtaining high-quality crystallization kinetic data with a small number of experiments. This approach can thus save significant experimental effort and time in the development of crystallization processes. 

A generalized schematic diagram for feedforward/feedback control of particle size in a continuous or semicontinuous crystallizer, such as that in Fig. 7-5, is shown in Fig. 7-6. The measurement device can be most easily envisioned as an in-line particle size analyzer such as a Lasentec focused beam reflectance measurement (FBRM), but it could also be a sampler/ offline device combination (even a plain microscope). The most common variant on this control schematic would be elimination of feedforward control, and perhaps of the fines trap as well. 

Focused beam reflectance measurement (FBRM) particle size (chord length) distribution... 

Since the inherent growth rate of many organic compounds is relatively slow, addition times may be long in order to achieve supersaturation control within the metastable zone. Higher addition rates can result in nucleation and the creation of a bimodal distribution. Experimentation to determine acceptable addition rates can be evaluated by focused beam reflectance measurement (FBRM) and other in-sim, online methods (Chapter 2) or microscopic observation of the crystal slurry which could reveal the presence of fines. These issues are highhghted in the examples below. 

NIR = near infrared spectroscopy, IR = infrared spectroscopy, UV= ultraviolet spectroscopy, Raman = Raman spectroscopy, FBRM = focused beam reflectance measurement,... 

Blanco, A., de la Fuente, E., Negro, C. et al. (2002) Focused beam reflectance measurement as a tool to measure flocculation. TAPPI Journal, 1 (10), 14-20. 

Kougoulos, E., Jones, A.G., Jennings, K.H. and Wood-Kaczmar, M.W. (2005) Use of focused beam reflectance measurement (FBRM) and process video imaging (PVI) in amodified mixed suspension mixed product removal (MSMPR) cooling crystallizer. J Crystal Growth, 273 (3-4), 529-534. 

More recently, there have been in-process techniques developed. Focused Beam Reflectance Measurement (FBRN ) uses an immersion probe and is capable of in situ measurement of particle chord length. Obscuration measurement can also be used as an in line size measurement. Acoustic size measurement is also emerging as in-process technique that permits use in heavy slurries that are difficult to measure using optical techniques. 

There are techniques available that allow accurate monitoring of the actual crystallisation process. The first and most widespread is focused beam reflectance measurement (FBRM). In FBRM, a spinning laser tracks across the surface of any particle at its focal point. The reflectance from the particle returns to a detector and the duration of this reflectance is known as a chord length (Fig. 9.12). 

Lasentec MIOOC Particle Geometry Monitor. The Lasentec MlOO monitor uses an FBRM (Focused Beam Reflectance Measurement) technique to measure the rate and degree of change to the particle population and Particle Geometry (a function of the shape and dimension of the particles and agglomerates as they naturally exist in... 

FBRM Focused beam reflectance measurement Change in partide dimension and particle count... 

Su et al. [24] studied the polymorphic transformation of n-mannitol by in situ Raman spectroscopy coupled with FBRM (focused beam reflectance measurement) and PVM (particle vision measurement). In this way, relationships between fine particles and metastable-form dissolution, and also between coarse particles and stable-form crystallization, could be defined. The different polymorphs were identified by Raman spectroscopy. FBRM provided a method for independently verifying these observations. PVM, in turn, verified the data interpretation strategy employed for FBRM. 

In addition to the characterization of the product, the characterization of the system during the crystallization process may be very important as it may help to ensure a stable and controlled crystallization process leading to material of the desired quality. A number of methods have been adapted for online use. These include XRPD, IR, ultrasound absorption, and Fraunhofer diffraction. The most commonly and conveniently used ones are turbidity, NIR, Raman, FBRM (focused beam reflectance measurement), and PVM (particle vision measurement). 

Figure 6.15. In the Lasentec Focused Beam Reflectance Measurement system the probe is i nserted in a stream of flnepartides and the rocadi optics scan the laser beam across flneparticles that pass in front of the probes window.

Thermodynamic parameters and spectroscopic data can also be monitored simultaneously during a process. For example, during fluid bed granulation, thermodynamic parameters such as temperature, relative humidity, and differential pressure in the vessel may be critical to the process. Parameters derived from inline sensors may include moisture content (via NIRS) and particle size (via focused beam reflection measurement, FBRM). Figure 6 represents a schematic of the... 

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