LPT-2009-04   BibTeX

@ARTICLE{LPT-2009-04,
AUTHOR = {N. Kail and H. Briesen and W. Marquardt},
TITLE = {{Process analysis by means of focused beam reflectance measurements}},
JOURNAL = {Industrial {\&} Engineering Chemistry Research},
YEAR = {2008},
volume = {48},
number = {6},
pages = {2936–2946 },
month = {},
note = {},
abstract = {Especially for the production of active pharmaceutical ingredients, the use of process analytical technology (PAT) is highly encouraged by the U.S. Food and Drug Administration. In crystallization and granulation processes in-situ particle characterization is the most important process analytical technology. Focused Beam Reflectance Measurements (FBRM) are very well suited for in-situ particle characterization. A large community of users successfully applies the FBRM technology for monitoring, fault detection and quality control of dynamic processes. However, FBRM measurements are not easy to interpret as the measured chord length distribution (CLD) is different from any kind of particle size distribution (PSD). For monitoring purposes, moments of the PSD are usually correlated empirically to moments of the CLD. Alternatively, process phenomena such as nucleation and growth can be attributed to the time evolution of the number of chords detected in a length interval. No publication known to the author deals with the accuracy of such correlations or presents a methodology to set the boundaries for the chord length intervals. In this work, a mathematical method is presented with which a set of measured CLDs can be reduced to a small number of chord length classes such that the class boundaries are chosen in an optimal way. The method relies either on a simulation using the optical FBRM model presented in earlier work (Kail et al. 2008) or on reference experiments. With the presented methods a batch crystallization of $\alpha$-lactose monohydrate and a precipitation of calcium carbonate are analyzed. Additionally, measurement artifacts of an FBRM are explained and discussed. },
keywords = {FBRM, PVM, PAT, process analytical technology, chord length distribution, lactose, calcium carbonate},
}

Norbert Kail, Heiko Briesen, Wolfgang Marquardt:

## Process analysis by means of focused beam reflectance measurements

Industrial & Engineering Chemistry Research, 2008, 48(6), 2936–2946

Abstract:
Especially for the production of active pharmaceutical ingredients, the use of process analytical technology (PAT) is highly encouraged by the U.S. Food and Drug Administration. In crystallization and granulation processes in-situ particle characterization is the most important process analytical technology. Focused Beam Reflectance Measurements (FBRM) are very well suited for in-situ particle characterization. A large community of users successfully applies the FBRM technology for monitoring, fault detection and quality control of dynamic processes. However, FBRM measurements are not easy to interpret as the measured chord length distribution (CLD) is different from any kind of particle size distribution (PSD). For monitoring purposes, moments of the PSD are usually correlated empirically to moments of the CLD. Alternatively, process phenomena such as nucleation and growth can be attributed to the time evolution of the number of chords detected in a length interval. No publication known to the author deals with the accuracy of such correlations or presents a methodology to set the boundaries for the chord length intervals. In this work, a mathematical method is presented with which a set of measured CLDs can be reduced to a small number of chord length classes such that the class boundaries are chosen in an optimal way. The method relies either on a simulation using the optical FBRM model presented in earlier work (Kail et al. 2008) or on reference experiments. With the presented methods a batch crystallization of $\alpha$-lactose monohydrate and a precipitation of calcium carbonate are analyzed. Additionally, measurement artifacts of an FBRM are explained and discussed.

Keywords:
FBRM, PVM, PAT, process analytical technology, chord length distribution, lactose, calcium carbonate