Study on Co-Crystallization of LCZ696 Using In Situ ATR-FTIR and Imaging
In situ ATR-FTIR spectroscopy and imaging and image analysis were applied to the study of the multicomponent co-crystallization process involving <i>S</i>-valsartan and sacubitril in which LCZ696 crystals were formed. LCZ696 is a combination drug for use in heart failure that was approve...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-10-01
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| Series: | Crystals |
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| Online Access: | https://www.mdpi.com/2073-4352/10/10/922 |
| _version_ | 1797551309514080256 |
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| author | Xiao Juan Liu Yang Zhang Xue Zhong Wang |
| author_facet | Xiao Juan Liu Yang Zhang Xue Zhong Wang |
| author_sort | Xiao Juan Liu |
| collection | DOAJ |
| description | In situ ATR-FTIR spectroscopy and imaging and image analysis were applied to the study of the multicomponent co-crystallization process involving <i>S</i>-valsartan and sacubitril in which LCZ696 crystals were formed. LCZ696 is a combination drug for use in heart failure that was approved by the FDA in 2015 following development by Novartis Pharmaceuticals. Though much work was reported on LCZ696 about its pharmacokinetic and pharmacodynamic effects in the evaluation and clinical testing, less attention was paid to study on the co-crystallization process. LCZ696 crystals have shown difficulties in filtration mainly due to the small particle size. In this work, LCZ696 crystals were prepared successfully by <i>S</i>-valsartan and sacubitril, and characterized by SEM, XRPD, TG-DSC and ATR-FTIR. ATR-FTIR and imaging and image analysis were used to monitoring solution concentration and investigating the co-crystallization mechanism. It revealed that the nucleation process was very slow compared with the transformation process, which is indication that the co-crystallization was controlled by nucleation. LCZ696 crystals are composed of very thin hexagonal plates, which seems indicating that LCZ696 crystals grow mainly in two size dimensions. Stirrer speed and crystal seeds were found to have noticeable effect on the induction time, transformation time and crystal size distribution. The Johnson-Mehl-Avrami equation was found to be able to describe the co-crystallization process. |
| first_indexed | 2024-03-10T15:42:48Z |
| format | Article |
| id | doaj.art-be4833378de74ced93b21d7b624fb3be |
| institution | Directory Open Access Journal |
| issn | 2073-4352 |
| language | English |
| last_indexed | 2024-03-10T15:42:48Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Crystals |
| spelling | doaj.art-be4833378de74ced93b21d7b624fb3be2023-11-20T16:40:52ZengMDPI AGCrystals2073-43522020-10-01101092210.3390/cryst10100922Study on Co-Crystallization of LCZ696 Using In Situ ATR-FTIR and ImagingXiao Juan Liu0Yang Zhang1Xue Zhong Wang2School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510641, ChinaSchool of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510641, ChinaLaboratory for Pharmaceutical and Crystallization Systems Engineering, Beijing Key Laboratory of Enze Biomass Fine Chemicals, School of Chemical Engineering, Beijing University of Petrochemical Technology, Beijing 102617, ChinaIn situ ATR-FTIR spectroscopy and imaging and image analysis were applied to the study of the multicomponent co-crystallization process involving <i>S</i>-valsartan and sacubitril in which LCZ696 crystals were formed. LCZ696 is a combination drug for use in heart failure that was approved by the FDA in 2015 following development by Novartis Pharmaceuticals. Though much work was reported on LCZ696 about its pharmacokinetic and pharmacodynamic effects in the evaluation and clinical testing, less attention was paid to study on the co-crystallization process. LCZ696 crystals have shown difficulties in filtration mainly due to the small particle size. In this work, LCZ696 crystals were prepared successfully by <i>S</i>-valsartan and sacubitril, and characterized by SEM, XRPD, TG-DSC and ATR-FTIR. ATR-FTIR and imaging and image analysis were used to monitoring solution concentration and investigating the co-crystallization mechanism. It revealed that the nucleation process was very slow compared with the transformation process, which is indication that the co-crystallization was controlled by nucleation. LCZ696 crystals are composed of very thin hexagonal plates, which seems indicating that LCZ696 crystals grow mainly in two size dimensions. Stirrer speed and crystal seeds were found to have noticeable effect on the induction time, transformation time and crystal size distribution. The Johnson-Mehl-Avrami equation was found to be able to describe the co-crystallization process.https://www.mdpi.com/2073-4352/10/10/922<i>S</i>-valsartan and sacubitril co-crystallizationLCZ696ATR-FTIROn-line process imaging |
| spellingShingle | Xiao Juan Liu Yang Zhang Xue Zhong Wang Study on Co-Crystallization of LCZ696 Using In Situ ATR-FTIR and Imaging Crystals <i>S</i>-valsartan and sacubitril co-crystallization LCZ696 ATR-FTIR On-line process imaging |
| title | Study on Co-Crystallization of LCZ696 Using In Situ ATR-FTIR and Imaging |
| title_full | Study on Co-Crystallization of LCZ696 Using In Situ ATR-FTIR and Imaging |
| title_fullStr | Study on Co-Crystallization of LCZ696 Using In Situ ATR-FTIR and Imaging |
| title_full_unstemmed | Study on Co-Crystallization of LCZ696 Using In Situ ATR-FTIR and Imaging |
| title_short | Study on Co-Crystallization of LCZ696 Using In Situ ATR-FTIR and Imaging |
| title_sort | study on co crystallization of lcz696 using in situ atr ftir and imaging |
| topic | <i>S</i>-valsartan and sacubitril co-crystallization LCZ696 ATR-FTIR On-line process imaging |
| url | https://www.mdpi.com/2073-4352/10/10/922 |
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