Monday, 23 May 2005

This presentation is part of: Bench Top to Pilot Plant Posters

Solvent swap tracking using an in-situ Foss Near-IR probe

Charles Van Kirk, Elias Mattas, Ehrlic Lo, Scott Savage, and Shih-Ying Chang. Bristol-Myers Squibb, New Brunswick, NJ

The distillation process is found in nearly every API formation. Usually this process has been modified many times from the original discovery process due to cost considerations, equipment availability and solvent selection. For example, while using roto-evaporation to remove excessive solvent may be the optimal technique in the lab, such a technique is unreasonable to use at the pilot plant scale. In order to circumvent this obstacle, a solvent swap is used to replace the initial solvent with a solvent that the sample would be more stable in, thus increasing yield or improving upon the processability of the product.

Presented here is an alternative to the traditional off-line analysis techniques with an in-situ near-infrared (NIR) process analytical technology (PAT). The use of the NIR probe to monitor the changing concentration of the distillate can be used to correlate back to the amount present in the mother liquor. In order to provide quantitative assessment of the distillate, a chemometric model was developed based on a GC analyzed calibration set of samples. This model was then able to provide immediate process feedback and could accurately predict the concentration of the target solvent (RMSEP < 0.1 % by volume in the range of 0 to 50 % v/v). This PAT technique enabled the process to be continuously monitored during the solvent swap and enable for immediate process adjustment (e.g., increasing pressure/temperature) by providing real-time analysis during the distillation. As such, unnecessary handling and exposure of the operators to the batch were prevented.

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