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目的:阐明不同来源普伐他汀钠原料药的晶型现状,建立不同晶型状态的有效检测方法,探讨不同来源普伐他汀钠原料的质量、疗效与其晶型状态的关系。方法:采用粉末X射线衍射分析法(PXRD法)、红外光谱分析法(IR法)、差示扫描量热法(DSC法)等对不同来源的原料样品进行晶型表征,采用动态水分吸附技术(DVS技术)对不同来源样品的水分吸附特性进行分析,并采用整体动物完成其生物学评价。结果:发现不同来源普伐他汀钠原料药的晶型状态不同,其中样品a、b、c均含有不同含量的晶A型,而样品d为晶F型;样品d的引湿速率较样品a、b、c大;生物学研究显示不同来源的普伐他汀钠原料药在主要药代动力学参数呈现显著的差异性,其中T_(max)、AUC、C_(max)的最大差异分别达到2.5,1.8,1.3倍之多。结论:采用PXRD法、IR法、DSC法均可实现对不同来源普伐他汀钠原料晶型状态的有效鉴别,稳定性、生物吸收、引湿性等分析研究结果表明晶A型优于晶F型。
OBJECTIVE: To elucidate the crystalline forms of pravastatin sodium APIs from different sources and to establish effective detection methods for different crystal forms, and to investigate the relationship between the quality and efficacy of pravastatin sodium raw materials and their crystalline forms. Methods: Raw material samples of different origins were characterized by powder X-ray diffraction (PXRD), infrared spectroscopy (IR) and differential scanning calorimetry (DSC). The dynamic water adsorption (DVS technique) was used to analyze the water sorption characteristics of samples from different sources and the whole animal was used to complete its biological evaluation. Results: The crystalline forms of pravastatin sodium from different sources were found to be different. Samples a, b and c contained different crystal forms A, and sample d was crystal F; the wetting rate of sample d was higher than that of sample a , B, c; biological studies have shown that different sources of pravastatin sodium API showed significant differences in the main pharmacokinetic parameters, in which T max, AUC, C max max difference of 2.5 , 1.8,1.3 times as many. Conclusion: The results of PXRD, IR and DSC showed that the crystalline forms of pravastatin sodium from different sources were effectively identified, the stability, bioabsorption and hygroscopicity were studied. The results showed that crystalline form A was superior to crystalline form F .