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Analysis of the crystallization process of a biopharmaceutical compound in the presence of impurities using process analytical technology (PAT) tools

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journal contribution
posted on 03.06.2016 by Elena Simone, Wei Zhang, Zoltan Nagy
BACKGROUND. The crystallization of biopharmaceuticals can be problematic since, because the biosynthesis of these compounds is very difficult to control, they can contain a significant amount of impurities that have to be eliminated. In fact, impurities can lead to changes in the properties of the drug that can significantly reduce its effectiveness or even put the user in danger. The aim of this work is to exploit process analytical technology (PAT) tools to study the crystallization step of vitamin B12 crude product extracted via fermentation. RESULTS. Linear cooling crystallization experiments were performed using different conditions. The effects of solvent, cooling rate, seeding and purity of the initial material on the final size distribution and purity of the crystals were investigated through the use of UV/Vis spectroscopy, focused beam reflectance measurement (FBRM) and the CryPRINS software (Crystallization Process Informatics System). It was found that impurities strongly inhibit the growth of vitamin B12 crystals, promoting nucleation and leading to poor final crystal size distribution. CONCLUSION. Slow cooling can help to increase the purity of the final product but also generates a broad crystal size distribution because of secondary nucleation. Preparing the solution with material already crystallized once and using purified seeds helped to obtain a narrower crystal size distribution and also to reduce breakage.

Funding

Financial support provided by the European Research Council grant no. [280106-CrySys].

History

School

  • Aeronautical, Automotive, Chemical and Materials Engineering

Department

  • Chemical Engineering

Published in

JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY

Volume

91

Issue

5

Pages

1461 - 1470 (10)

Citation

SIMONE, E., ZHANG, W. and NAGY, Z., 2016. Analysis of the crystallization process of a biopharmaceutical compound in the presence of impurities using process analytical technology (PAT) tools. Journal of Chemical Technology and Biotechnology, 91 (5), pp. 1461-1470.

Publisher

© John Wiley & Sons

Version

AM (Accepted Manuscript)

Publisher statement

This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/

Publication date

2016

Notes

This is the peer reviewed version of the following article: SIMONE, E., ZHANG, W. and NAGY, Z., 2016. Analysis of the crystallization process of a biopharmaceutical compound in the presence of impurities using process analytical technology (PAT) tools. Journal of Chemical Technology and Biotechnology, 91 (5), pp.1461-1470., which has been published in final form at http://dx.doi.org/10.1002/jctb.4743. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."

ISSN

0268-2575

eISSN

1097-4660

Language

en

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