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Abstract
Slurries are widely used in important chemical and pharmaceutical manufacturing processes. In this presentation we report chemical monitoring and modeling of batch slurry reactions using optical and calorimetric measurement where key analytes are present in both the solid and liquid phases. Experimental studies were performed to:
(1) Generate supersaturated solutions for the development of kinetic models of seeded crystallization, crystal growth, and dissolution;
(2) Generate unseeded crystallization from homogeneous reaction mixtures for the development of kinetic models of reacting systems, including crystal growth as well as measurement of crystallization driven by cooling of reaction mixtures including the necessary corresponding solubility curves as a function of temperature;
(3) Reproduce at laboratory scale, a commercially relevant slurry reaction starting with heterogeneous reaction mixture, producing a product slurry.
Simultaneous UV/visible attenuated total reflectance (ATR) and NIR reflectance measurements enabled reliable characterization of reaction mixtures and detection of the onset of crystallization. Kinetic models for dissolution, seeded crystallization, unseeded crystallization, homogeneous reaction and crystallization driven by cooling were successfully developed relating the mass of substance in the solution phase and solid phase to UV/Vis ATR and NIR reflectance measurements. Reactive crystallization experiments with kinetic modeling demonstrated that simultaneous measurements of slurries with UV/Vis ATR and NIR reflectance is an effective means of characterizing the dissolved fraction and the onset of nucleation and crystallization.
Work with research partner DuPont Crop Protection Science included development of a 4 L glass reactor with a recirculation loop and sampling system for off-line HPLC analysis. Several different sampling strategies were tested to develop a robust, reproducible method for off-line HPLC analysis. NIR reflectance measurements of slurry reactions at DuPont were demonstrated to be relevant to the property of interest. Kinetic models were obtained for product and reactant from NIR reflectance measurements. Reaction progression was followed by depletion of triazine heterocycle, as indicated by N-H overtone band dissipation. Spectroscopic evidence of a precipitation event was also observed and confirmed by focused beam reflectance measurements (FBRM). Kinetic models of reaction measurements provided clear resolution of two components, the solid phase reactant and solid phase product. Initial product appearance in the kinetic model concentration profile estimates corresponded temporally with the spectroscopic evidence of precipitation. Estimation of spectral profiles from kinetic models include an N-H overtone band observed around 2010nm.
(1) Generate supersaturated solutions for the development of kinetic models of seeded crystallization, crystal growth, and dissolution;
(2) Generate unseeded crystallization from homogeneous reaction mixtures for the development of kinetic models of reacting systems, including crystal growth as well as measurement of crystallization driven by cooling of reaction mixtures including the necessary corresponding solubility curves as a function of temperature;
(3) Reproduce at laboratory scale, a commercially relevant slurry reaction starting with heterogeneous reaction mixture, producing a product slurry.
Simultaneous UV/visible attenuated total reflectance (ATR) and NIR reflectance measurements enabled reliable characterization of reaction mixtures and detection of the onset of crystallization. Kinetic models for dissolution, seeded crystallization, unseeded crystallization, homogeneous reaction and crystallization driven by cooling were successfully developed relating the mass of substance in the solution phase and solid phase to UV/Vis ATR and NIR reflectance measurements. Reactive crystallization experiments with kinetic modeling demonstrated that simultaneous measurements of slurries with UV/Vis ATR and NIR reflectance is an effective means of characterizing the dissolved fraction and the onset of nucleation and crystallization.
Work with research partner DuPont Crop Protection Science included development of a 4 L glass reactor with a recirculation loop and sampling system for off-line HPLC analysis. Several different sampling strategies were tested to develop a robust, reproducible method for off-line HPLC analysis. NIR reflectance measurements of slurry reactions at DuPont were demonstrated to be relevant to the property of interest. Kinetic models were obtained for product and reactant from NIR reflectance measurements. Reaction progression was followed by depletion of triazine heterocycle, as indicated by N-H overtone band dissipation. Spectroscopic evidence of a precipitation event was also observed and confirmed by focused beam reflectance measurements (FBRM). Kinetic models of reaction measurements provided clear resolution of two components, the solid phase reactant and solid phase product. Initial product appearance in the kinetic model concentration profile estimates corresponded temporally with the spectroscopic evidence of precipitation. Estimation of spectral profiles from kinetic models include an N-H overtone band observed around 2010nm.