泰比培南酯细粒剂的关键质量属性研究

Study on the Critical Quality Attributes of Tebipenem Pivoxil Fine Granules

关键词:  泰比培南酯  细粒剂  关键质量属性  仿制药研发

Key words:  tebipenem pivoxil  fine granules  critical quality attributes  generic drug development

摘要:

目的 研发仿制药泰比培南酯细粒剂，并研究参比制剂的关键质量属性。方法 对泰比培南酯原料药进行溶解性、强制降解及不同溶剂中的溶液稳定性考察，并对泰比培南酯细粒剂的溶出曲线、粒度分布、有关物质和含量等关键质量属性进行考察研究。结果 原料药泰比培南酯极微溶于水，且溶解度具有pH依赖性，酸性越强，溶解度越大，但在pH 1.0和pH 2.0溶液中很快降解。参比制剂泰比培南酯细粒剂在酸性介质中释放迅速；粒度集中在30~120目之间；含量为100.8%；有关物质泰比培南含量为0.05%。结论 建立原料药和参比制剂的关键质量属性有助于泰比培南酯细粒剂的仿制药研发。

Abstract:

OBJECTIVE To research the critical quality attributes of reference listed drug, in order to develop the generic drug of tebipenem pivoxil fine granules. METHODS The critical quality attributes of the active pharmaceutical ingredient including solubility, stress testing and stability in different solvent were researched and evaluated. The critical quality attributes of reference listed drug of tebipenem pivoxil fine granules including dissolution, particle size distribution, related substance and assay were researched and evaluated as well. RESULTS The active pharmaceutical ingredient was very slightly soluble in water, and the solubility was pH-dependent. The stronger the acidity, the greater the solubility, but it quickly degraded in pH 1.0 and pH 2.0 solutions. The reference listed drug was dissolving rapidly in the acid medium, and most of the particle distributed in the range of 30 mesh to 120 mesh. The content was 100.8%, and the content of impurity tebipenem was 0.05%. CONCLUSION The critical quality attributes of active pharmaceutical ingredient and reference listed drug will help the development of generic drug of tebipenem pivoxil fine granules.