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). 2022;70(2):162-168. doi: 10.1248/cpb.c21-00975.
NMR relaxometry measurement by time domain NMR (TD-NMR) is a promising technique for characterizing the properties of active pharmaceutical ingredients (APIs). This study is dedicated to identifying the salt and free base of APIs by NMR relaxometry measured by the TD-NMR technique. Procaine (PC) and tetracaine (TC) were selected as model APIs to be tested. By using conventional methods including powder X-ray diffraction and differential scanning calorimetry, this study first confirmed that the salt and free base of the tested APIs differ from each other in their crystalline form. Subsequently, measurements of T and T relaxation were performed on the tested APIs using TD-NMR. The results demonstrated that these NMR relaxometry measurements have sufficient capacity to distinguish the difference between the free base and salt of the tested APIs. Furthermore, quantification of the composition of the binary powder blends consisting of salt and free bases was conducted by analyzing the acquired T and T relaxation curves. The analysis of the T relaxation curves provided a partly acceptable estimation: a good estimation of the composition was observed from PC powders, whereas for TC powders the estimation accuracy changed with the free base content in the binary blends. For the analysis on T relaxation curves, a precise estimation of the composition was observed from all the samples. From these findings, the NMR relaxometry measurement by TD-NMR, in particular the T relaxation measurement, is effective for evaluating the properties of APIs having different crystalline forms.
通过时域 NMR（TD-NMR）进行 NMR 弛豫测量是一种有前途的技术，可用于表征活性药物成分（API）的特性。本研究致力于通过 TD-NMR 技术测量的 NMR 弛豫来鉴定 API 的盐和游离碱。选择普鲁卡因（PC）和丁卡因（TC）作为测试的模型 API。通过使用包括粉末 X 射线衍射和差示扫描量热法在内的常规方法，本研究首先证实了测试的 API 的盐和游离碱在其晶体形式上彼此不同。随后，使用 TD-NMR 对测试的 API 进行 T1 和 T2 弛豫测量。结果表明，这些 NMR 弛豫测量具有足够的能力来区分测试 API 的游离碱和盐之间的差异。此外，通过分析获得的 T1 和 T2 弛豫曲线，对由盐和游离碱组成的二元粉末混合物的组成进行了定量。T1 弛豫曲线的分析提供了部分可接受的估计：从 PC 粉末中观察到了组成的良好估计，而对于 TC 粉末，估计准确性随二元混合物中游离碱的含量而变化。对于 T2 弛豫曲线的分析，所有样品均观察到了精确的组成估计。从这些发现中，可以看出，通过 TD-NMR 进行的 NMR 弛豫测量，特别是 T1 弛豫测量，对于评估具有不同晶体形式的 API 的特性是有效的。
