Laboratory of Pharmaceutical Technology, School of Pharmacy and Pharmaceutical Sciences, University of Toyama.
Formulation Development Department, Development & Planning Division, Nichi-Iko Pharmaceutical Co., Ltd.
Chem Pharm Bull (Tokyo). 2024;72(7):676-680. doi: 10.1248/cpb.c24-00215.
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 relaxation of EZT monohydrate and anhydrate was measured without a humidity controller. The T relaxation results confirmed that EZT anhydrate and monohydrate could be distinguished using T 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 relaxation measurement was repeated while maintaining the humidity on the side entering the NMR tube at 80% relative humidity. The T relaxation became gradually faster from the initial to middle monitoring phases. The final T relaxation was then recovered fully and these T relaxation times were the same as the T relaxation of EZT monohydrate. This study successfully monitored the pseudopolymorphic transition from EZT anhydrate to monohydrate via NMR relaxation.
本研究旨在通过使用时域 NMR（TD-NMR）测量 NMR 弛豫来连续监测无定形向一水合物的假多晶型转变。利用低场 NMR 仪器配置简单的优势（这是 TD-NMR 的优势之一），将 NMR 仪器连接到湿度控制器上以监测假多晶型转变。首先，使用饱和盐溶液法从埃替拉韦（EZT）无水物制备 EZT 一水合物，并在没有湿度控制器的情况下测量 EZT 一水合物和无水物的 T 弛豫。T 弛豫结果证实，T 弛豫测量可以区分 EZT 无水物和一水合物。接下来，通过 TD-NMR 进行连续监测，并连接到湿度控制器。将无水 EZT 放置在 NMR 玻璃管中，并在 NMR 管侧保持 80%相对湿度的情况下重复 T 弛豫测量。从初始监测阶段到中间监测阶段，T 弛豫逐渐变快。最后，T 弛豫完全恢复，这些 T 弛豫时间与 EZT 一水合物的 T 弛豫时间相同。本研究成功地通过 NMR 弛豫监测了 EZT 无水物向一水合物的假多晶型转变。
