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Preventing crystal agglomeration of pharmaceutical crystals using temperature cycling and a novel membrane crystallization procedure for seed crystals generation

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posted on 30.01.2018, 14:45 by Elena Simone, Rahimah Othman, Goran Vladisavljevic, Zoltan Nagy
In this work, a novel membrane crystallization system was used to crystallize micro-sized seeds of piroxicam monohydrate by reverse antisolvent addition. Membrane crystallization seeds were compared with seeds produced by conventional antisolvent addition and polymorphic transformation of a fine powdered sample of piroxicam form I in water. The membrane crystallization process allowed for a consistent production of pure monohydrate crystals with narrow size distribution and without significant agglomeration. The seeds were grown in 350 g of 20:80 w/w acetone-water mixture. Different seeding loads were tested and temperature cycling was applied in order to avoid agglomeration of the growing crystals during the process. Focused beam reflectance measurement (FBRM); and particle vision and measurement (PVM) were used to monitor crystal growth; nucleation and agglomeration during the seeded experiments. Furthermore; Raman spectroscopy was used to monitor solute concentration and estimate the overall yield of the process. Membrane crystallization was proved to be the most convenient and consistent method to produce seeds of highly agglomerating compounds; which can be grown via cooling crystallization and temperature cycling.

Funding

Financial support was provided by the European Research Council grant no. [280106-CrySys]. R. Othman gratefully acknowledges the financial support given for this work through the Ministry of Higher Education Malaysia.

History

School

  • Aeronautical, Automotive, Chemical and Materials Engineering

Department

  • Chemical Engineering

Published in

Pharmaceutics

Volume

10

Issue

1

Pages

1 - 15

Citation

SIMONE, E. ...et al., 2018. Preventing crystal agglomeration of pharmaceutical crystals using temperature cycling and a novel membrane crystallization procedure for seed crystals generation. Pharmaceutics, 10: 17.

Publisher

© the Authors. Published by MDPI AG

Version

VoR (Version of Record)

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/

Acceptance date

24/01/2018

Publication date

2018

Notes

This is an Open Access Article. It is published by MDPI under the Creative Commons Attribution 4.0 Unported Licence (CC BY). Full details of this licence are available at: http://creativecommons.org/licenses/by/4.0/

ISSN

1999-4923

Language

en

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