基于拉曼光谱技术药物包衣厚度分布预测模型的构建  

Model construction for drug coating thickness distribution prediction based on Raman spectroscopy

作　　者：王学重 王亦卓 张冉 侯光昊 吴韬 WANG Xuezhong;WANG Yizhuo;ZHANG Ran;HOU Guanghao;WU Tao(Beijing Key Laboratory of Enze Biomass Fine Chemicals,College of New Materials and Chemical Engineering,Beijing institute of Petrochemical Technology,Beijing 102617,China)

机构地区：[1]北京石油化工学院新材料与化工学院,恩泽生物质精细化工北京市重点实验室,北京102617

出　　处：《高校化学工程学报》2024年第5期781-787,共7页Journal of Chemical Engineering of Chinese Universities

基　　金：北京市科技新星计划(Z211100002121024)。

摘　　要：为了实现药物包衣层厚度分布的实时在线检测,解决离线检测平均厚度或称重不能满足均匀性分析及判断终点等问题,以蛋白哂双凸片的包衣过程为例,采用探头式拉曼光谱仪实时在线采集片剂表面拉曼光谱的同时,离线采集并统计包衣层厚度分布。分别采用偏最小二乘法(PLS)和卷积神经网络(CNN)两种方法建立包衣厚度定量校正模型。结果表明,PLS模型预测相关性Rp2为0.923,CNN模型Rp2高达0.996,其模型的泛化能力更高,较PLS模型展现出更好的准确性。且CNN模型预测的包衣层厚度分布与离线统计的厚度分布结果较为一致(包衣时间为60 min,最可几厚度和分布宽度偏差仅为0.44%和1.24%),实现了药物包衣层厚度分布的准确预测。In order to real-time monitor drug coating thickness distribution and overcome the drawbacks of offline measurements of average thickness and weight(which cannot satisfy the requirements of coating uniformity analysis and endpoint judgement of drug coating),a Raman spectrometer was used to collect Raman spectra of table surface in-line and real-time using selenium tablet coating as a reference.Meanwhile,the coating thickness distribution was also statistically analyzed by a microscope.Two modeling approaches including partial least squares(PLS)and convolutional neural network(CNN)were applied to build coating thickness calibration model.The correlation coefficient of determination Rp 2 of PLS model was 0.923,and the Rp 2 of CNN was 0.996.CNN model shows higher generation capability and accuracy than PLS model.Furthermore,coating thickness distribution predicted by CNN model is in accordance with the offline results(errors of most probable thickness and distribution width at coating time of 60 min were 0.44%and 1.24%,respectively).Therefore,drug coating thickness distribution can be accurately predicted by Raman spectroscopy combined with CNN model.

关 键 词：在线拉曼光谱 包衣厚度统计分布 偏最小二乘法 主成分分析-卷积神经网络 包衣均匀性 

分 类 号：TQ469[化学工程—制药化工]