Wide-Ranging Molecular Mobilities of Water in Active Pharmaceutical Ingredient (API) Hydrates as Determined by NMR Relaxation Times

In order to examine the possibility of determining the molecular mobility of hydration water in active pharmaceutical ingredient (API) hydrates by NMR relaxation measurement, spin–spin relaxation and spin–lattice relaxation were measured for the 11 API hydrates listed in the Japanese Pharmacopeia using pulsed 1H-NMR. For hydration water that has relatively high mobility and shows Lorentzian decay, molecular mobility as determined by spin–spin relaxation time (T2) was correlated with ease of evaporation under both nonisothermal and isothermal conditions, as determined by DSC and water vapor sorption isotherm analysis, respectively. Thus, T2 may be considered a useful parameter which indicates the molecular mobility of hydration water. In contrast, for hydration water that has low mobility and shows Gaussian decay, T2 was found not to correlate with ease of evaporation under nonisothermal conditions, which suggests that in this case, the molecular mobility of hydration water was too low to be determined by T2. A wide range of water mobilities was found among API hydrates, from low mobility that could not be evaluated by NMR relaxation time, such as that of the water molecules in pipemidic acid hydrate, to high mobility that could be evaluated by this method, such as that of the water molecules in ceftazidime hydrate.