New Techniques for Solid-State NMR Studies of Pharmaceuticals

堪萨斯大学的Eric J. Munson教授得到了分析和表面化学项目的支持，以开发使用固态核磁共振光谱（SSNMR）改进药物分析的方法。构建了一种包含多个自旋系统的魔角自旋核磁共振探针。探针设计使纺丝系统能够快速穿梭于静态磁场的均匀区域。当获得一个样品的光谱时，其他样品的磁化强度在磁场的非均匀区域恢复平衡。与传统的MAS探针相比，多样品能力提高了灵敏度和吞吐量。该项目还在调查与新药物化合物的配方有关的基本问题。一个领域侧重于提高固态核磁共振光谱的能力，以识别、检测和量化药物固体的多晶态、溶剂化物和非晶态。另一个是确定弛豫和线宽与药物的物理化学性质（如粒度和晶体缺陷）之间的关系。第三个领域是将从测量的核磁共振参数中获得的知识应用于药物稳定性，最终目标是使用固态核磁共振作为早期识别稳定配方的预测工具。正在开发的SSNMR技术为药物制剂的表征提供了新的工具。这些进步也可以广泛应用于药物和样品的分析，包括玻璃、聚合物和催化剂。该项目为研究生提供培训，并促进与制药业的合作。

Professor Eric J. Munson of the University of Kansas is supported by the Analytical and Surface Chemistry program to develop methods to improve the analysis of pharmaceuticals using solid-state NMR spectroscopy (SSNMR). A magic-angle spinning (MAS) NMR probe that contains multiple spinning systems is being constructed. The probe design enables the spinning systems to be rapidly shuttled in and out of the homogeneous region of the static magnetic field. While the spectrum of one sample is being acquired, the magnetization of the other samples are returning to equilibrium in the inhomogeneous region of the field. The multiple sample capabilities increase sensitivity and throughput compared to conventional MAS probes. The project is also investigating fundamental problems related to the formulation of new drug compounds. One area focuses on improving the capabilities of solid-state NMR spectroscopy to identify, detect, and quantify polymorphs, solvates, and amorphous forms of a pharmaceutical solid. Another is determining how relaxation and line width are related to the physicochemical properties of the drug, such as particle size and crystal defects. A third area is applying the knowledge gained from measured NMR parameters to drug stability, with the ultimate goal of using solid-state NMR as a predictive tool for early identification of stable formulations.The SSNMR technology being developed is providing new tools for the characterization of drug formulations. The advances can also be applied broadly to the analysis of pharmaceuticals and samples that include glasses, polymers, and catalysts. The project is providing training for graduate students and enabling collaborations with the pharmaceutical industry.