Novel Cocrystals of Vonoprazan: Machine Learning-Assisted Discovery
Vonoprazan (VPZ) is the first-in-class potassium-competitive acid blocker (P-CAB), and has many advantages over proton pump inhibitors (PPIs). It is administered as a fumarate salt for the treatment of acid-related diseases, including reflux esophagitis, gastric ulcer, and duodenal ulcer, and for er...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/2/429 |
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| author | Min-Jeong Lee Ji-Yoon Kim Paul Kim In-Seo Lee Medard E. Mswahili Young-Seob Jeong Guang J. Choi |
| author_facet | Min-Jeong Lee Ji-Yoon Kim Paul Kim In-Seo Lee Medard E. Mswahili Young-Seob Jeong Guang J. Choi |
| author_sort | Min-Jeong Lee |
| collection | DOAJ |
| description | Vonoprazan (VPZ) is the first-in-class potassium-competitive acid blocker (P-CAB), and has many advantages over proton pump inhibitors (PPIs). It is administered as a fumarate salt for the treatment of acid-related diseases, including reflux esophagitis, gastric ulcer, and duodenal ulcer, and for eradication of <i>Helicobacter pylori</i>. To discover novel cocrystals of VPZ, we adopted an artificial neural network (ANN)-based machine learning model as a virtual screening tool that can guide selection of the most promising coformers for VPZ cocrystals. Experimental screening by liquid-assisted grinding (LAG) confirmed that 8 of 19 coformers selected by the ANN model were likely to create new solid forms with VPZ. Structurally similar benzenediols and benzenetriols, i.e., catechol (CAT), resorcinol (RES), hydroquinone (HYQ), and pyrogallol (GAL), were used as coformers to obtain phase pure cocrystals with VPZ by reaction crystallization. We successfully prepared and characterized three novel cocrystals: VPZ–RES, VPZ–CAT, and VPZ–GAL. VPZ–RES had the highest solubility among the novel cocrystals studied here, and was even more soluble than the commercially available fumarate salt of VPZ in solution at pH 6.8. In addition, novel VPZ cocrystals had superior stability in aqueous media than VPZ fumarates, demonstrating their potential for improved pharmaceutical performance. |
| first_indexed | 2024-03-09T21:13:44Z |
| format | Article |
| id | doaj.art-28cc6672f2df4b55a64d417756c17449 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T21:13:44Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-28cc6672f2df4b55a64d417756c174492023-11-23T21:39:12ZengMDPI AGPharmaceutics1999-49232022-02-0114242910.3390/pharmaceutics14020429Novel Cocrystals of Vonoprazan: Machine Learning-Assisted DiscoveryMin-Jeong Lee0Ji-Yoon Kim1Paul Kim2In-Seo Lee3Medard E. Mswahili4Young-Seob Jeong5Guang J. Choi6Department of Pharmaceutical Engineering, Soonchunhyang University, Asan 31538, Chungnam, KoreaDepartment of Medical Science, Soonchunhyang University, Asan 31538, Chungnam, KoreaDepartment of Medical Science, Soonchunhyang University, Asan 31538, Chungnam, KoreaDepartment of Medical Science, Soonchunhyang University, Asan 31538, Chungnam, KoreaDepartment of ICT Convergence, Soonchunhyang University, Asan 31538, Chungnam, KoreaDepartment of Computer Engineering, Chungbuk National University, Cheongju 28644, Chungbuk, KoreaDepartment of Pharmaceutical Engineering, Soonchunhyang University, Asan 31538, Chungnam, KoreaVonoprazan (VPZ) is the first-in-class potassium-competitive acid blocker (P-CAB), and has many advantages over proton pump inhibitors (PPIs). It is administered as a fumarate salt for the treatment of acid-related diseases, including reflux esophagitis, gastric ulcer, and duodenal ulcer, and for eradication of <i>Helicobacter pylori</i>. To discover novel cocrystals of VPZ, we adopted an artificial neural network (ANN)-based machine learning model as a virtual screening tool that can guide selection of the most promising coformers for VPZ cocrystals. Experimental screening by liquid-assisted grinding (LAG) confirmed that 8 of 19 coformers selected by the ANN model were likely to create new solid forms with VPZ. Structurally similar benzenediols and benzenetriols, i.e., catechol (CAT), resorcinol (RES), hydroquinone (HYQ), and pyrogallol (GAL), were used as coformers to obtain phase pure cocrystals with VPZ by reaction crystallization. We successfully prepared and characterized three novel cocrystals: VPZ–RES, VPZ–CAT, and VPZ–GAL. VPZ–RES had the highest solubility among the novel cocrystals studied here, and was even more soluble than the commercially available fumarate salt of VPZ in solution at pH 6.8. In addition, novel VPZ cocrystals had superior stability in aqueous media than VPZ fumarates, demonstrating their potential for improved pharmaceutical performance.https://www.mdpi.com/1999-4923/14/2/429pharmaceutical cocrystalvonoprazanP-CABmachine learningstability |
| spellingShingle | Min-Jeong Lee Ji-Yoon Kim Paul Kim In-Seo Lee Medard E. Mswahili Young-Seob Jeong Guang J. Choi Novel Cocrystals of Vonoprazan: Machine Learning-Assisted Discovery Pharmaceutics pharmaceutical cocrystal vonoprazan P-CAB machine learning stability |
| title | Novel Cocrystals of Vonoprazan: Machine Learning-Assisted Discovery |
| title_full | Novel Cocrystals of Vonoprazan: Machine Learning-Assisted Discovery |
| title_fullStr | Novel Cocrystals of Vonoprazan: Machine Learning-Assisted Discovery |
| title_full_unstemmed | Novel Cocrystals of Vonoprazan: Machine Learning-Assisted Discovery |
| title_short | Novel Cocrystals of Vonoprazan: Machine Learning-Assisted Discovery |
| title_sort | novel cocrystals of vonoprazan machine learning assisted discovery |
| topic | pharmaceutical cocrystal vonoprazan P-CAB machine learning stability |
| url | https://www.mdpi.com/1999-4923/14/2/429 |
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