Loughborough University
Browse

File(s) under permanent embargo

Reason: This item is currently closed access.

Application of process analytical technology-based feedback control strategies to improve purity and size distribution in biopharmaceutical crystallization

journal contribution
posted on 2016-06-03, 12:20 authored by Elena Simone, Wei Zhang, Zoltan NagyZoltan Nagy
Purity is a critical quality attribute for both pharmaceutical and biopharmaceutical products. The presence of impurities (solvents, salts or byproducts of the synthetic path) in drugs can cause a reduction of their effectiveness or can even be toxic for the patients. Biopharmaceuticals are produced by biological processes which are difficult to control. Therefore the amount of impurities that has to be removed can be significantly higher than in the case of synthetic pharmaceuticals. The aim of this work is to exploit process analytical technology (PAT) tools and different feedback control strategies (T-control, direct nucleation control and supersaturation control) for the crystallization of a biopharmaceutical product. UV/Vis spectroscopy, focused beam reflectance measurement (FBRM) combined with a 2 crystallization process informatics system (CryPRINS) were used to improve the crystal size distribution and purity of crystallized vitamin B12. The different feedback control strategies were compared to classical crystallization techniques in terms of purity of the final crystal and quality of the crystal size distribution and it is shown that using suitable crystallization feedback control strategies, the purity and quality of crystals can be improved.

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

CRYSTAL GROWTH & DESIGN

Volume

15

Issue

6

Pages

2908 - 2919 (12)

Citation

SIMONE, E., ZHANG, W. and NAGY, Z.K., 2015. Application of process analytical technology-based feedback control strategies to improve purity and size distribution in biopharmaceutical crystallization. Crystal Growth & Design, 15(6), pp. 2908-2919.

Publisher

© American Chemical Society

Version

  • SMUR (Submitted Manuscript Under Review)

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

2015

Notes

This paper is in closed access.

ISSN

1528-7483

Language

  • en

Usage metrics

    Loughborough Publications

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC