Quantitation of crystalline and amorphous forms of anhydrous neotame using 13C CPMAS NMR spectroscopy.
Quantitation of crystalline and amorphous forms of anhydrous neotame using 13C CPMAS NMR spectroscopy.
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DOI：
10.1002/jps.20469
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发表时间：
2005-12
影响因子：
3.8
通讯作者：
Thomas J Offerdahl;Jonathon S. Salsbury;Zedong Dong;D. Grant;S. Schroeder;I. Prakash;Eric M. Gorman;D. H. Barich;E. Munson
中科院分区：
文献类型：
--
作者：
Thomas J Offerdahl;Jonathon S. Salsbury;Zedong Dong;D. Grant;S. Schroeder;I. Prakash;Eric M. Gorman;D. H. Barich;E. Munson
虽然大多数药物是以结晶状态配制的，但在配制过程中往往会产生无定形或其他结晶形式。其他形式的存在会极大地影响药物的物理和化学稳定性。鉴别和定量一种不同形式的药物是一项重大的分析挑战，尤其是在配方产品中。介绍了采用交叉极化(CP)和魔角旋转(MAS)的固体~(13)C核磁共振波谱对人工甜味剂纽甜的三种多晶型和非晶型进行定量的能力。在两种无水多晶型纽甜的混合物中，有可能将每一种多晶型的数量量化在1-2%内。在无定形和结晶型纽甜的混合物中，无定形含量可测定到5%以内。研究发现，用于制备混合物的结晶标准不是纯结晶形式，而是结晶和非晶态的混合物。讨论了结晶标准中非晶态含量对两种晶型的总体定量的影响。在使用固体核磁共振波谱定量不同形式的混合物时，还讨论了松弛参数和CP效率的差异的重要性。
Although most drugs are formulated in the crystalline state, amorphous or other crystalline forms are often generated during the formulation process. The presence of other forms can dramatically affect the physical and chemical stability of the drug. The identification and quantitation of different forms of a drug is a significant analytical challenge, especially in a formulated product. The ability of solid-state 13C NMR spectroscopy with cross polarization (CP) and magic-angle spinning (MAS) to quantify the amounts of three of the multiple crystalline and amorphous forms of the artificial sweetener neotame is described. It was possible to quantify, in a mixture of two anhydrous polymorphic forms of neotame, the amount of each polymorph within 1-2%. In mixtures of amorphous and crystalline forms of neotame, the amorphous content could be determined within 5%. It was found that the crystalline standards that were used to prepare the mixtures were not pure crystalline forms, but rather a mixture of crystalline and amorphous forms. The effect of amorphous content in the crystalline standards on the overall quantitation of the two crystalline polymorphic forms is discussed. The importance of differences in relaxation parameters and CP efficiencies on quantifying mixtures of different forms using solid-state NMR spectroscopy is also addressed.