Robust Bayesian estimation of kinetics for the polymorphic transformation of L-glutamic acid crystals

• Published in: AIChE journal 2008-12, Vol.54 (12), p.3248-3259
• Main Authors: Hermanto, Martin Wijaya, Kee, Nicholas C, Tan, Reginald B.H, Chiu, Min-Sen, Braatz, Richard D
• Format: Article
• Language: English
• Subjects: Analytical chemistry; Applied sciences; Bayesian inference; Chemical engineering; Crystallization; Crystallization, leaching, miscellaneous separations; Exact sciences and technology; Markov analysis; Markov Chain Monte Carlo; Monte Carlo simulation; pharmaceutical crystallization modeling; Polymorphism; Reaction kinetics; Robust control
• ISSN: 0001-1541; 1547-5905
• DOI: 10.1002/aic.11623

Polymorphism, in which there exist different crystal forms for the same chemical compound, is an important phenomenon in pharmaceutical manufacturing. In this article, a kinetic model for the crystallization of L-glutamic acid polymorphs is developed from experimental data. This model appears to be the first to include all of the transformation kinetic parameters including dependence on the temperature. The kinetic parameters are estimated by Bayesian inference from batch data collected from two in situ measurements: ATR-FTIR spectroscopy is used to infer the solute concentration, and FBRM that provides crystal size information. Probability distributions of the estimated parameters in addition to their point estimates are obtained by Markov Chain Monte Carlo simulation. The kinetic model can be used to better understand the effects of operating conditions on crystal quality, and the probability distributions can be used to assess the accuracy of model predictions and incorporated into robust control strategies for polymorphic crystallization. © 2008 American Institute of Chemical Engineers AIChE J, 2008