Characterization of the Salt and Free Base of Active Pharmaceutical Ingredients Based on NMR Relaxometry Measured by Time Domain NMR

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 T1 and T2 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 T1 and T2 relaxation curves. The analysis of the T1 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 T2 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 T2 relaxation measurement, is effective for evaluating the properties of APIs having different crystalline forms.