{"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}
引用次数: 0
Abstract
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.
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