{"title":"利用时域 NMR 的 T1 弛豫连续监测依折麦布的假多晶型转变","authors":"Takashi Ono, Kotaro Okada, Misaki Kaga, Hidekatsu Eto, Shungo Kumada, Nobuyuki Wakui, Yoshinori Onuki","doi":"10.1248/cpb.c24-00215","DOIUrl":null,"url":null,"abstract":"<p><p>The purpose of this study was to continuously monitor the pseudopolymorphic transition from anhydrate to monohydrate by measuring the NMR relaxation using time-domain NMR (TD-NMR). Taking advantage of the simplicity of the low-field NMR instrument configuration, which is an advantage of TD-NMR, the NMR instrument was connected to a humidity controller to monitor the pseudopolymorphic transition. First, ezetimibe (EZT) monohydrate was prepared from its anhydrate using a saturated salt solution method, and T<sub>1</sub> relaxation of EZT monohydrate and anhydrate was measured without a humidity controller. The T<sub>1</sub> relaxation results confirmed that EZT anhydrate and monohydrate could be distinguished using T<sub>1</sub> relaxation measurement. Next, continuous monitoring was conducted by TD-NMR and connected to a humidity controller. Anhydrous EZT was placed in an NMR glass tube and the T<sub>1</sub> relaxation measurement was repeated while maintaining the humidity on the side entering the NMR tube at 80% relative humidity. The T<sub>1</sub> relaxation became gradually faster from the initial to middle monitoring phases. The final T<sub>1</sub> relaxation was then recovered fully and these T<sub>1</sub> relaxation times were the same as the T<sub>1</sub> relaxation of EZT monohydrate. This study successfully monitored the pseudopolymorphic transition from EZT anhydrate to monohydrate via NMR relaxation.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.5000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Continuous Monitoring of Pseudopolymorphic Transition in Ezetimibe Using T<sub>1</sub> Relaxation with Time-Domain NMR.\",\"authors\":\"Takashi Ono, Kotaro Okada, Misaki Kaga, Hidekatsu Eto, Shungo Kumada, Nobuyuki Wakui, Yoshinori Onuki\",\"doi\":\"10.1248/cpb.c24-00215\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The purpose of this study was to continuously monitor the pseudopolymorphic transition from anhydrate to monohydrate by measuring the NMR relaxation using time-domain NMR (TD-NMR). Taking advantage of the simplicity of the low-field NMR instrument configuration, which is an advantage of TD-NMR, the NMR instrument was connected to a humidity controller to monitor the pseudopolymorphic transition. First, ezetimibe (EZT) monohydrate was prepared from its anhydrate using a saturated salt solution method, and T<sub>1</sub> relaxation of EZT monohydrate and anhydrate was measured without a humidity controller. The T<sub>1</sub> relaxation results confirmed that EZT anhydrate and monohydrate could be distinguished using T<sub>1</sub> relaxation measurement. Next, continuous monitoring was conducted by TD-NMR and connected to a humidity controller. Anhydrous EZT was placed in an NMR glass tube and the T<sub>1</sub> relaxation measurement was repeated while maintaining the humidity on the side entering the NMR tube at 80% relative humidity. The T<sub>1</sub> relaxation became gradually faster from the initial to middle monitoring phases. The final T<sub>1</sub> relaxation was then recovered fully and these T<sub>1</sub> relaxation times were the same as the T<sub>1</sub> relaxation of EZT monohydrate. This study successfully monitored the pseudopolymorphic transition from EZT anhydrate to monohydrate via NMR relaxation.</p>\",\"PeriodicalId\":9773,\"journal\":{\"name\":\"Chemical & pharmaceutical bulletin\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chemical & pharmaceutical bulletin\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1248/cpb.c24-00215\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chemical & pharmaceutical bulletin","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1248/cpb.c24-00215","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
摘要
本研究的目的是通过使用时域核磁共振(TD-NMR)测量核磁共振弛豫来连续监测从无水物到一水物的假多晶型转变。利用低场 NMR 仪器配置简单这一 TD-NMR 的优势,将 NMR 仪器连接到湿度控制器上,以监测伪多晶型转变。首先,使用饱和盐溶液法从其无水物制备了依折麦布(EZT)一水物,并在不使用湿度控制器的情况下测量了 EZT 一水物和无水物的 T1 弛豫。T1 弛豫结果证实,可以通过 T1 弛豫测量来区分 EZT 一水合物和一水合物。接下来,使用 TD-NMR 并连接湿度控制器进行连续监测。将无水 EZT 放入 NMR 玻璃管中,重复进行 T1 驰豫测量,同时将进入 NMR 管一侧的湿度保持在相对湿度 80%。从最初监测阶段到中期监测阶段,T1 驰豫速度逐渐加快。最后 T1 弛豫完全恢复,这些 T1 弛豫时间与一水 EZT 的 T1 弛豫时间相同。这项研究成功地通过核磁共振弛豫监测了 EZT 从无水物到一水物的假多晶型转变。
Continuous Monitoring of Pseudopolymorphic Transition in Ezetimibe Using T1 Relaxation with Time-Domain NMR.
The purpose of this study was to continuously monitor the pseudopolymorphic transition from anhydrate to monohydrate by measuring the NMR relaxation using time-domain NMR (TD-NMR). Taking advantage of the simplicity of the low-field NMR instrument configuration, which is an advantage of TD-NMR, the NMR instrument was connected to a humidity controller to monitor the pseudopolymorphic transition. First, ezetimibe (EZT) monohydrate was prepared from its anhydrate using a saturated salt solution method, and T1 relaxation of EZT monohydrate and anhydrate was measured without a humidity controller. The T1 relaxation results confirmed that EZT anhydrate and monohydrate could be distinguished using T1 relaxation measurement. Next, continuous monitoring was conducted by TD-NMR and connected to a humidity controller. Anhydrous EZT was placed in an NMR glass tube and the T1 relaxation measurement was repeated while maintaining the humidity on the side entering the NMR tube at 80% relative humidity. The T1 relaxation became gradually faster from the initial to middle monitoring phases. The final T1 relaxation was then recovered fully and these T1 relaxation times were the same as the T1 relaxation of EZT monohydrate. This study successfully monitored the pseudopolymorphic transition from EZT anhydrate to monohydrate via NMR relaxation.
期刊介绍:
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