关键词:  , 尼可地尔片；杂质谱；生产工艺；原辅料相容性；包材

Abstract:

Objective： To investigate the impurity profiles of Nicorandil tablets and to study the effects of formulation， production process and packaging materials on the impurity profiles.Methods： High performance liquid chromatography （HPLC） was used to determine the impurity content and liquid-mass spectrometry （LMS） was used for structure confirmation. Through the investigation of intermediates， temperature and humidity influencing factors， correlation between moisture and related substances and the influence of packaging materials， the sources of impurities were deduced from the comprehensive analysis of 88 batches of domestic Nicorandil tablets from 2 enterprises， 3 batches of raw materials and 8 batches of original formulation， and the targeted preventive and control measures were put forward according to the causes of the impurities.Results： A total of 6 main impurities （ impurity A to impurity F） were detected. The impurity C， impurity D and impurity F of Nicorandil tablets increase significantly in high temperature and high humidity environment. The content of impurity A， impurity B， impurity C， impurity D and impurity F in the samples were positively correlated with the moisture content. The presence of hygroscopic excipients in the formulation will directly lead to the increase of impurity content.Conclusion： In the production of Nicorandil tablets， wet granulation process should be avoided， and the use of excipients with strong hygroscopicity should be avoided in the formulation. It is recommended to use double aluminium foil plate and aluminium foil bag （with high efficient desiccant inside） to help avoid degradation of Nicorandil tablets， and to avoid high temperature and high humidity environment in the storage.

Key words: Nicorandil tablets； , Impurity profile； , Production process； , Drug-excipients compatibility； , Packaging materials