有指导的正交投影技术结合斜率/截距校正法实现小试水分近红外定量模型向中试传递

针对小试制剂过程建立的近红外定量模型难以直接应用于中试或大生产过程中的问题,该文以小试和中试条件下多批次药用糊精流化床制粒过程为载体,在线采集其近红外光谱数据并测定水分含量,建立小试过程水分近红外定量模型,提出并应用有指导的正交投影技术结合斜率/截距校正的模型传递方法跨尺度预测中试样本,使中试两个测试集A和B的水分相对预测误差分别由51.04%和26.64%降至4.90%和3.99%,显著提高了模型预测的准确度。将该结果与无指导的正交投影技术结合斜率/截距校正法以及模型更新相比较,该方法能更加有效地去除待测样本光谱中的干扰信息,适用范围广,为小试建立的模型放大应用到中试甚至大生产过程提供了新方案。

Achievement of Moisture Transfer of Near Infrared Quantitative Model from Small-test Preparation Process to Pilot-test by Directed Direct Orthogonal Signal Correction Combined with Slope/Bias Correction

The near infrared quantitative model established through the small test preparation process is difficult to apply in the pilot or large scale production process directly,which discourage the development of near infrared spectroscopy in the pharmaceutical preparation process.To solve this problem,the fluidized bed granulation process with medicinal dextrin was adopted in this paper.Meanwhile,the NIR spectrum data and the moisture contents of samples in the above preparation process experienced both the small test and the pilot test were collected.Then the near infrared quantitative model for moisture content was established with 3 batches of samples in small test.Based on this,a model transfer method,directed direct orthogonal signal correction combined with slope/bias correction(DDOSC-SBC) was proposed to predict the moisture content of pilot samples.The relative standard errors of prediction for two separate pilot test sets were decreased from 51.04% and 26.64% to 4.90% and 3.99%,respectively after using this directed model-transfer method.Compared with undirected direct orthogonal projection technique combined with slope/bias correction(DOSC-SBC) and the model update,this method could remove the interference spectrum information from pilot test samples more effectively.Consequently,this method provides a new idea for application of the near infrared quantitative model transitting from small test to pilot test or even expanding to the large scale production process.