chemproc-09-00021.pdf (6.86 MB)
Targeting desired particle size for improved dissolution and manufacturability of mefenamic acid
conference contribution
posted on 2022-09-28, 12:26 authored by Wei LiWei Li, Chris RiellyChris Rielly, Brahim BenyahiaBrahim BenyahiaThis 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
Find out more...History
School
- Aeronautical, Automotive, Chemical and Materials Engineering
Department
- Chemical Engineering
Published in
Chemistry ProceedingsVolume
9Issue
1Source
3rd International Online Conference on CrystalsPublisher
MDPIVersion
- VoR (Version of Record)
Rights holder
© The AuthorsPublisher 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
2022-01-15Copyright date
2022eISSN
2673-4583Publisher version
Language
- en