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Systematic model-based steady state and dynamic optimization of combined cooling and antisolvent multistage continuous crystallization processes

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conference contribution
posted on 2021-01-05, 14:29 authored by Jiaxu Liu, Brahim BenyahiaBrahim Benyahia
Currently, one of the key challenges in the pharmaceutical industry is the transformation of traditional batch production methods into robust continuous processes with the intention of reducing manufacturing costs and time and improving product quality. Crystallization is by far the most important purification technology in Pharma, as more than 80% of the active pharmaceutical ingredients (API) require at least one crystallization step. A successful crystallization process requires tight control over crystal size, shape and polymorphic purity. A rigorous and systematic methodology is presented to design and optimize multistage combined cooling and antisolvent continuous (mixed-suspension, mixed-product removal- MSMPR) crystallizers. The crystallization of acetylsalicylic acid (API) in ethanol (solvent) and water (anti-solvent) is used as a case study. A predictable and validated mathematical model of the system, which consists of a one-dimensional population balance model, was used to develop several optimizations strategies. Firstly, the attainable region of the mean particle size was determined for both minimum and maximum attainable crystal size. The method helped identify the most suitable number of stages and total residence time or volume for a cascade of continuous crystallizers. This was followed by a steady state optimization which helped determine the optimal operating temperatures and antisolvent flowrates. To minimize the startup time, a series of dynamic optimization strategies were implemented, assuming starting from empty vessels. The optimal dynamic profiles of the temperature and antisolvent flow rate, at different crystallization steps, were identified using a systematic and rigorous approach allowing a reduction in the startup time by 31%.

History

School

  • Aeronautical, Automotive, Chemical and Materials Engineering

Department

  • Chemical Engineering

Published in

Proceedings

Volume

62

Issue

1

Source

The 2nd International Online Conference on Crystals

Publisher

MDPI

Version

  • VoR (Version of Record)

Rights holder

© The authors

Publisher statement

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/

Acceptance date

2020-10-01

Publication date

2020-12-31

Copyright date

2020

Notes

This article belongs to the Proceedings of The 2nd International Online Conference on Crystals

ISSN

2504-3900

Language

  • en

Location

Online

Event dates

10th November 2020 - 20th January 2021

Depositor

Dr Brahim Benyahia. Deposit date: 1 January 2021

Article number

7

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