Optimal Control of Antisolvent and Cooling Crystallization
Zhou, Lifang
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https://hdl.handle.net/2142/18493
Description
Title
Optimal Control of Antisolvent and Cooling Crystallization
Author(s)
Zhou, Lifang
Issue Date
2011-01-21T22:42:45Z
Director of Research (if dissertation) or Advisor (if thesis)
Braatz, Richard D.
Department of Study
Chemical & Biomolecular Engr
Discipline
Chemical Engineering
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
M.S.
Degree Level
Thesis
Keyword(s)
Antisolvent crystallization
cooling crystallization
dual impinging jet
Y-mixer
paracetamol
Feedback Control
Abstract
Common quality requirements for crystallization products is so critical in the pharmaceutical industry, including the demands of the drug administration and customers (e.g. bioavailability, size uniformity, and polymorphic form) and the concern of the manufacturer for downstream processes such as filtration and drying (e.g. ability to flow). Because crystal size distribution (CSD) has a large effect on crystal properties, reproducible and optimal control of the CSD is of great importance.
The first part of this thesis collected ATR-FTIR spectra and built a calibration model, whose regression coefficients were used along with ATR-FTIR spectra to measure the solubility of paracetamol in isopropanol-water solution at various temperatures and solvent ratios, also for further feedback control study. The second part simulated the process of feeding seeds produced by real-time antisolvent crystallization to cooling tank to decouple nucleation and growth. Optimization of the temperature profiles to achieve targeted crystal size distributions was presented as well.
The overall contribution of the thesis is the development of a new process: the combination of antisovlent crystallization in dual impinging jet crystallizer and cooling crystallization in tank, which can be used to develop a continuous crystallization method in industry.
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