Continuous Plug Flow Crystallization of Pharmaceutical Compounds
Name
Myerson_Plug Flow Crystallization paper final revision to submit.pdf
Description
main article
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220.25 KB
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Adobe PDF
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Author(s)
Alvarez, Alejandro J.
Myerson, Allan S.
Date Issued
March 2010
Journal
Crystal Growth and Design
Publisher
American Chemical Society
Citation
Alvarez, Alejandro J., and Allan S. Myerson. “Continuous Plug Flow Crystallization of Pharmaceutical Compounds.” Crystal Growth & Design 10.5 (2010): 2219-2228.
Version
Author's final manuscript
Abstract
Crystallization processes in the pharmaceutical industry are usually designed to obtain crystals with controlled size, shape, purity, and polymorphic form. Knowledge of the process conditions required to fabricate crystals with controlled characteristics is critical during process development. In this work, continuous crystallization of ketoconazole, flufenamic acid, and l-glutamic acid in a nonconventional plug flow crystallizer was investigated. Kenics type static mixers were used to promote homogeneous mixing of active pharmaceutical ingredient solution and antisolvent. A strategy of multiple points of addition of antisolvent along the crystallizer was evaluated to control the size of the crystals. Interestingly, it was found that crystal size can be increased or decreased with an increased number of antisolvent addition points, depending on the kinetics of the system. It was also found that smaller crystals with a narrower size distribution can be obtained with the static mixers. A model to describe the continuous crystallization process was developed through the simultaneous solution of a population balance equation, kinetics expressions for crystal growth and nucleation, and a mass balance. The comparison of experimental and calculated values for crystal size distribution revealed that a growth rate dispersion model could describe accurately the continuous crystallization process. Collision of crystals with each other and with mixing elements inside the crystallizer may be the source of random fluctuation of the growth rate in the nonconventional plug flow crystallizer with static mixers.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
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DOI of Published Version
https://doi.org/10.1021/cg901496s
