277096 PAT for Multiphase Reaction Mixtures

Wednesday, October 31, 2012
Hall B (Convention Center )
Jacob Albrecht, Gregory Lane, Mark Lindrud and Srinivas Tummala, Chemical Development, Bristol-Myers Squibb Co., New Brunswick, NJ

Spectroscopic PAT techniques offer real-time monitoring of pharmaceutical processes, providing valuable process information and an opportunity for feedback control.  However, reactions commonly encountered in API synthetic processes are frequently heterogeneous, containing two or more phases that can interfere with and reduce the sensitivity of techniques such as Raman and FTIR spectroscopy.

This paper reports the use of an intermediate filter layer to remove unwanted phases from real-time analysis.  Removing this interference has been shown to dramatically reduce signal noise for binary and ternary phase systems by selectively passing only one of the phases to the sensing region of the PAT probe.  Because of the local continuous phase separation [1], we evaluated the potential impact of sensor delay.  Fortunately, we found the observed sensor delay to be insignificant relative to typical reaction times.  For a desired analyte, the theory guiding the selection of filter material based on surface energy and porosity will be discussed, as well as opportunities for improvement and implementation on a manufacturing scale.


[1] Kralj, J.G.; Sahoo,H. R.; Jensen, K. F.,  Integrated continuous microfluidic liquid-liquid extraction  Lab Chip 2007, 7, 256–263

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