基于图像导向的拉曼光谱技术研究来氟米特片的溶出曲线差异

目的：分析引起国产来氟米特片与参比制剂（SANOFI）溶出曲线差异的影响因素。方法：采用图像导向的拉曼光谱Morphologi G3-ID颗粒表征系统分析来氟米特片的崩解液，先用光学成像系统测量崩解液中颗粒的粒径和形状参数，然后采用拉曼光谱区分崩解液中API颗粒和辅料颗粒，获得API颗粒的粒度和粒形分布结果，并比较国产来氟米特片和参比制剂在崩解后的粒径和粒形差异。结果：国产来氟米特片崩解液中来氟米特API粒径D（v，50）为79.8 μm，参比制剂崩解液中API粒径D（v，50）为17.6 μm；且国产来氟米特片崩解液中发现较多API颗粒与辅料呈包结大颗粒状态。结论：国内外产品溶出曲线差异较大，建议生产企业在开展该品种仿制药质量一致性评价时，应进一步优化处方、生产工艺。

Objective:To analyze the influence factor causing the dissolution profile difference between domestic leflunomide tablets and reference product.Method:The leflunomide tablets after disintegrating was analyzed by Morphologi G3-ID automated measurement with image orientation of Raman spectroscopy;First measuring leflunomide after disintegration with optical imaging system in particle size and shape parameter,then using Raman spectroscopy to distinguish the disintegrating API particles and excipients particles,to get the paricile size and size distribution result of the API particle,and compare the particle size and shape difference between the disintegration solution of reference and domestic procucts.Results:The particle size D (v,50)of domestic leflunomide tablets was 79.8 μm,while the particle size D (v,50)of reference product was 17.6 μm;and there was a lot of big particles agglomerated by API with excipients in domestic product disintegration solution.Conclusion:There is a lot of difference between domestic and reference products in dissolution profile,suggesting the manufacturing enterprises to optimize the prescription and production process during the quality consistency evaluation.

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