Considerations in Raman Spectroscopy for Real-Time API Concentration Measurement at Tablet Press Feed Frame

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2023-02-16 DOI:10.1155/2023/8631288

S Kumar, Zoltan K. Nagy, G. Reklaitis, Marcial Gonzalez

{"title":"Considerations in Raman Spectroscopy for Real-Time API Concentration Measurement at Tablet Press Feed Frame","authors":"S Kumar, Zoltan K. Nagy, G. Reklaitis, Marcial Gonzalez","doi":"10.1155/2023/8631288","DOIUrl":null,"url":null,"abstract":"Raman spectroscopy is one of the important process analytical technology tools available for implementation in the continuous manufacturing of oral solid dosages. The aim of this study was to investigate several practical considerations in generating real-time measurements using Raman spectrometer at a tablet press feed frame, including the effects of fluorescence interference, photobleaching, feed-frame rpm, and material particle size. Fluorescence, in particular, is a significant drawback of Raman spectroscopy, compared to the use of near-infrared spectroscopy. Potential material sparing strategies were also investigated, including using stationary powders for calibration and isolation of feed-frame materials. Acetaminophen was used as the main active pharmaceutical ingredient (API), and microcrystalline cellulose (MCC) and lactose were used as excipients. The fluorescent behavior of MCC at 785 nm laser wavelength was reported and discussed. Raman spectra of a blend of MCC and acetaminophen and lactose and acetaminophen were collected at the feed frame of the tablet press. A series of preprocessing steps applied to remove the fluorescence interference was found to be effective, including the use of standard normal variate, subtraction of spectra of fluorescent material, baseline correction, and smoothing. Three different PLS models were prepared for different scenarios and their performances were compared. The models were able to predict the concentration of acetaminophen with root mean squared error prediction (RMSEP) of 0.29% w/w when there was no fluorescence interference and 0.57% w/w when there was fluorescence interference in background spectra. The study demonstrated the feasibility of using Raman spectroscopy for API concentration prediction even in the case of fluorescent interference and showed that Raman measurements were robust; that is, they were not much affected by feed-frame rpm and excipient particle size.","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":null,"pages":null},"PeriodicalIF":16.4000,"publicationDate":"2023-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Accounts of Chemical Research","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1155/2023/8631288","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}

引用次数: 1

Abstract

Raman spectroscopy is one of the important process analytical technology tools available for implementation in the continuous manufacturing of oral solid dosages. The aim of this study was to investigate several practical considerations in generating real-time measurements using Raman spectrometer at a tablet press feed frame, including the effects of fluorescence interference, photobleaching, feed-frame rpm, and material particle size. Fluorescence, in particular, is a significant drawback of Raman spectroscopy, compared to the use of near-infrared spectroscopy. Potential material sparing strategies were also investigated, including using stationary powders for calibration and isolation of feed-frame materials. Acetaminophen was used as the main active pharmaceutical ingredient (API), and microcrystalline cellulose (MCC) and lactose were used as excipients. The fluorescent behavior of MCC at 785 nm laser wavelength was reported and discussed. Raman spectra of a blend of MCC and acetaminophen and lactose and acetaminophen were collected at the feed frame of the tablet press. A series of preprocessing steps applied to remove the fluorescence interference was found to be effective, including the use of standard normal variate, subtraction of spectra of fluorescent material, baseline correction, and smoothing. Three different PLS models were prepared for different scenarios and their performances were compared. The models were able to predict the concentration of acetaminophen with root mean squared error prediction (RMSEP) of 0.29% w/w when there was no fluorescence interference and 0.57% w/w when there was fluorescence interference in background spectra. The study demonstrated the feasibility of using Raman spectroscopy for API concentration prediction even in the case of fluorescent interference and showed that Raman measurements were robust; that is, they were not much affected by feed-frame rpm and excipient particle size.

查看原文本刊更多论文

拉曼光谱在压片机进料框实时测量API浓度的考虑

拉曼光谱是用于口服固体制剂连续生产的重要过程分析技术工具之一。本研究的目的是探讨在压片机进料框上使用拉曼光谱仪进行实时测量时的几个实际考虑因素，包括荧光干涉、光漂白、进料框转速和材料粒度的影响。与使用近红外光谱相比，荧光是拉曼光谱的一个显着缺点。潜在的材料节约策略也进行了研究，包括使用固定粉末进行校准和隔离料框材料。以对乙酰氨基酚(API)为主要活性药物成分，微晶纤维素(MCC)和乳糖为辅料。报道并讨论了MCC在785 nm激光波长下的荧光行为。在压片机进料架上采集了MCC与对乙酰氨基酚、乳糖与对乙酰氨基酚的共混物的拉曼光谱。一系列的预处理步骤用于消除荧光干扰被发现是有效的，包括使用标准正态变量，光谱的荧光材料，基线校正和平滑。针对不同的场景制备了三种不同的PLS模型，并对其性能进行了比较。在无荧光干扰时，模型预测对乙酰氨基酚浓度的均方根误差预测值(RMSEP)为0.29% w/w;在有荧光干扰时，模型预测对乙酰氨基酚浓度的均方根误差预测值为0.57% w/w。该研究表明，即使在荧光干扰的情况下，拉曼光谱用于API浓度预测的可行性，并表明拉曼测量是稳健的;也就是说，它们不太受进料框转速和辅料粒度的影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.