利用近红外一致性检验方法验证药品标准物质包装的密闭性

目的:建立近红外一致性检验方法,用于快速检查药品标准物质组合包装(西林瓶、胶塞、铝塑盖)的密闭性,进而保证国家药品标准物质的质量。方法:选择易引湿的溴化钾作为试验样品,使用积分球方法采集近红外漫反射光谱,以2名不同操作人员测定的未引湿样品光谱为参照光谱,谱图经矢量归一化、一阶导数和17点平滑处理后,在谱段5326~4825 cm^-1和4632~4377 cm^-1建立一致性检验模型,阈值设定为4。在检查西林瓶组合包装密闭性时,将分装有未吸水溴化钾样品且包装完好的玻璃瓶放入密闭92%RH的高湿环境中24 h后,测定其近红外光谱,带入一致性检验模型,通过比较待测光谱与参照光谱的差异来判断其是否引湿,即密闭性是否有问题。结果:应用所建立的一致性检验模型分别预测正常样品和模拟包装密闭性有问题的样品,结果与实际情况一致。结论:所建一致性检验模型可以对组合包装密闭性有问题的样品做出准确的判断,可用于药品标准物质筛选西林瓶、胶塞和组合包装工艺的验证。

Objective:To establish a near infrared(NIR) conformity test method for rapidly checking the combination package(vials,rubber closures and aluminum-plastic lids) seal quality,so as to guarantee the quality of the national drug standard materials in its storage duration.Methods:Potassium bromide(KBr) was selected to model construction due to its hygroscopicity.The NIR diffuse reflectance spectra were recorded by integrating sphere,and the data of the dried KBr collected by 2 persons were used as calibration samples.All the spectra were pretreated by first derivate with 17-points smoothing followed by vector normalization.Then,a conformity test model was constructed at the spectral regions of 5 326-4 825 cm^-1 and 4 632-4 377 cm^-1,and the threshold was set as 4.When checking the seal quality of the combination package,firstly the dried KBr powder was put into the combination package,secondly these vials with KBr were stored in a closed environment of 92% RH for 24 h,and then the vials were taken out to record their NIR spectra.By comparing these spectra and the reference spectra of the calibration samples using conformity test model,we can judge whether the dried KBr absorbed water and the tested combination package has seal problems.Results:The conformity test method was validated by real samples and some simulated samples with poor package seal quality.All the prediction results were consistent with their actual situation of these samples.Conclusion:The constructed conformity test method can give accurate results for the combination package seal quality of drug reference standards.In addition,this method can be used for packaging process validation of drug reference standards,which may help us for screening the suitable combination package of vials,rubber closures and aluminum-plastic lids.