End-to-End Continuous Small-Scale Drug Substance Manufacturing: From a Continuous In Situ Nucleator to Free-Flowing Crystalline Particles
In the evolving landscape of pharmaceutical manufacturing, a comprehensive continuous production process is being crafted for the small-scale production of active pharmaceutical ingredients. This study focuses on continuous crystallization with separate nucleation and crystal growth units, as well a...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-12-01
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| Series: | Crystals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4352/13/12/1675 |
| _version_ | 1797381475504488448 |
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| author | Anne Cathrine Kufner Marc Meier Kerstin Wohlgemuth |
| author_facet | Anne Cathrine Kufner Marc Meier Kerstin Wohlgemuth |
| author_sort | Anne Cathrine Kufner |
| collection | DOAJ |
| description | In the evolving landscape of pharmaceutical manufacturing, a comprehensive continuous production process is being crafted for the small-scale production of active pharmaceutical ingredients. This study focuses on continuous crystallization with separate nucleation and crystal growth units, as well as continuous downstream processing, encompassing filtration, washing, and drying until the formation of free-flowing particles. We introduce a novel continuous nucleator designed based on solubility data and produced via 3D printing, enabling the fast and precise small-scale manufacturing of a nucleator meeting the requirements for nucleation and further growth processes. The nucleator is evaluated with regard to its suitability for continuous long-term operation across various coupled crystallizers. As a practical application example, it is connected to a slug flow crystallizer to enable high-quality continuous crystallization. Additionally, the full integration of downstream processes using a continuous vacuum screw filter to achieve free-flowing product particles is realized. Even under non-optimized process conditions, with the help of the in situ generation of nuclei, free-flowing product particles are successfully obtained. This is particularly useful during drug development when no material is available for seed addition and to quickly obtain products for further characterization. |
| first_indexed | 2024-03-08T20:53:02Z |
| format | Article |
| id | doaj.art-b8f6ceb50b4e429290a287f1b944df72 |
| institution | Directory Open Access Journal |
| issn | 2073-4352 |
| language | English |
| last_indexed | 2024-03-08T20:53:02Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Crystals |
| spelling | doaj.art-b8f6ceb50b4e429290a287f1b944df722023-12-22T14:01:58ZengMDPI AGCrystals2073-43522023-12-011312167510.3390/cryst13121675End-to-End Continuous Small-Scale Drug Substance Manufacturing: From a Continuous In Situ Nucleator to Free-Flowing Crystalline ParticlesAnne Cathrine Kufner0Marc Meier1Kerstin Wohlgemuth2Laboratory of Plant and Process Design, Department of Biochemical and Chemical Engineering, TU Dortmund University, D-44227 Dortmund, GermanyLaboratory of Plant and Process Design, Department of Biochemical and Chemical Engineering, TU Dortmund University, D-44227 Dortmund, GermanyLaboratory of Plant and Process Design, Department of Biochemical and Chemical Engineering, TU Dortmund University, D-44227 Dortmund, GermanyIn the evolving landscape of pharmaceutical manufacturing, a comprehensive continuous production process is being crafted for the small-scale production of active pharmaceutical ingredients. This study focuses on continuous crystallization with separate nucleation and crystal growth units, as well as continuous downstream processing, encompassing filtration, washing, and drying until the formation of free-flowing particles. We introduce a novel continuous nucleator designed based on solubility data and produced via 3D printing, enabling the fast and precise small-scale manufacturing of a nucleator meeting the requirements for nucleation and further growth processes. The nucleator is evaluated with regard to its suitability for continuous long-term operation across various coupled crystallizers. As a practical application example, it is connected to a slug flow crystallizer to enable high-quality continuous crystallization. Additionally, the full integration of downstream processes using a continuous vacuum screw filter to achieve free-flowing product particles is realized. Even under non-optimized process conditions, with the help of the in situ generation of nuclei, free-flowing product particles are successfully obtained. This is particularly useful during drug development when no material is available for seed addition and to quickly obtain products for further characterization.https://www.mdpi.com/2073-4352/13/12/1675continuous manufacturingcontinuous nucleation3D printingcontinuous downstreamsmall-scale productionhigh-quality products |
| spellingShingle | Anne Cathrine Kufner Marc Meier Kerstin Wohlgemuth End-to-End Continuous Small-Scale Drug Substance Manufacturing: From a Continuous In Situ Nucleator to Free-Flowing Crystalline Particles Crystals continuous manufacturing continuous nucleation 3D printing continuous downstream small-scale production high-quality products |
| title | End-to-End Continuous Small-Scale Drug Substance Manufacturing: From a Continuous In Situ Nucleator to Free-Flowing Crystalline Particles |
| title_full | End-to-End Continuous Small-Scale Drug Substance Manufacturing: From a Continuous In Situ Nucleator to Free-Flowing Crystalline Particles |
| title_fullStr | End-to-End Continuous Small-Scale Drug Substance Manufacturing: From a Continuous In Situ Nucleator to Free-Flowing Crystalline Particles |
| title_full_unstemmed | End-to-End Continuous Small-Scale Drug Substance Manufacturing: From a Continuous In Situ Nucleator to Free-Flowing Crystalline Particles |
| title_short | End-to-End Continuous Small-Scale Drug Substance Manufacturing: From a Continuous In Situ Nucleator to Free-Flowing Crystalline Particles |
| title_sort | end to end continuous small scale drug substance manufacturing from a continuous in situ nucleator to free flowing crystalline particles |
| topic | continuous manufacturing continuous nucleation 3D printing continuous downstream small-scale production high-quality products |
| url | https://www.mdpi.com/2073-4352/13/12/1675 |
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