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Targeting desired particle size for improved dissolution and manufacturability of mefenamic acid

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conference contribution
posted on 28.09.2022, 12:26 authored by Wei LiWei Li, Chris RiellyChris Rielly, Brahim BenyahiaBrahim Benyahia
This work aims at the production of uniformly sized, equant shaped crystals using a direct nucleation control (DNC) strategy to help achieve enhanced manufacturability and bioavailability of the active pharmaceutical ingredients (API). A crystallization system equipped with in-situ and external wet-milling devices was used. The experiments were conducted using mefenamic acid (MFA) in mixed solvents of 2-butanol and heptane with a mass ratio of 90:10. Firstly, a linear cooling crystallization was conducted as reference case and also to identify suitable DNC set-points, which were then implemented using closed-loop feedback control based on the measurement of the FBRM counts. The in-situ and external wet-milling based DNC approaches were compared in terms of temperature cycling efficiency and final crystal size and shape. This integrated wet-milling crystallization systems demonstrated enhanced control over the crystal size distribution (CSD) and morphology compared to the conventional cooling crystallization processes. In addition, the expansion of design space was achieved by integrating wet-mill to DNC crystallization compared to the cooling crystallization only process. Also, enhanced control of the rate of nucleation and attrition is accomplished through combing wet-milling and DNC operations.

Funding

Future Continuous Manufacturing and Advanced Crystallisation Research Hub

Engineering and Physical Sciences Research Council

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History

School

  • Aeronautical, Automotive, Chemical and Materials Engineering

Department

  • Chemical Engineering

Published in

Chemistry Proceedings

Volume

9

Issue

1

Source

3rd 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 International Licence (CC BY 4.0). Full details of this licence are available at: https://creativecommons.org/licenses/by/4.0/

Publication date

2022-01-15

Copyright date

2022

eISSN

2673-4583

Language

en

Location

Online

Event dates

15th January 2022 - 30th January 2022

Depositor

Dr Brahim Benyahia. Deposit date: 9 March 2022

Article number

21