Near infrared spectroscopy for blend uniformity monitoring: An innovative qualitative application based on the coefficient of determination

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2022-10-05 DOI:10.1177/09670335221130430

Y. Roggo, Lizbeth Martínez, A. Peinado, S. Matero

{"title":"Near infrared spectroscopy for blend uniformity monitoring: An innovative qualitative application based on the coefficient of determination","authors":"Y. Roggo, Lizbeth Martínez, A. Peinado, S. Matero","doi":"10.1177/09670335221130430","DOIUrl":null,"url":null,"abstract":"Blending process is a critical unit operation in the pharmaceutical industry during the solid dosage form production. Near infrared (NIR) spectroscopy is a powerful analytical tool to assess the blend homogeneity in real-time. In this paper, a new methodology for blending process monitoring and for end point confirmation is proposed. Quantitative procedure validation and maintenance of NIR procedures are time-consuming activities that can prevent the adoption of PAT tools in the pharmaceutical industry. Clearly, there is a need in the industry for simpler and more intuitive qualitative blend monitoring analytical procedure that are easy to build, validate and maintain. The method introduced herein consists of tracking the trend of the Coefficient of Determination (CD) between a mean reference spectrum from a homogeneous batch and the NIR spectra that are recorded during the blending operation. Four formulations of commercial products were selected from different scales–including low dosage solid form-to show the usefulness of the method. In addition, this analytical procedure is tested with data from two different types of spectrometers (diode array instruments). Method calibration was performed with five batches (representing expected process variability) for each product: one for the computation of the homogeneous batch target spectrum and four to compute the limit of the CD values related to anticipated and acceptable homogeneity. Method validation was performed with homogeneous batches and with challenge spectra for assessing the specificity of the method. Real-world examples (e.g. technical, validation batches and clinical batches) were presented in order to demonstrate that this method is able to detect inhomogeneous batches. The new qualitative method presented in this paper is useful for determination of the blending endpoint, in assessing the blend uniformity in real-time and in increasing process understanding during early development and troubleshooting. Graphical Abstract","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":null,"pages":null},"PeriodicalIF":16.4000,"publicationDate":"2022-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Accounts of Chemical Research","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1177/09670335221130430","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: 0

Abstract

Blending process is a critical unit operation in the pharmaceutical industry during the solid dosage form production. Near infrared (NIR) spectroscopy is a powerful analytical tool to assess the blend homogeneity in real-time. In this paper, a new methodology for blending process monitoring and for end point confirmation is proposed. Quantitative procedure validation and maintenance of NIR procedures are time-consuming activities that can prevent the adoption of PAT tools in the pharmaceutical industry. Clearly, there is a need in the industry for simpler and more intuitive qualitative blend monitoring analytical procedure that are easy to build, validate and maintain. The method introduced herein consists of tracking the trend of the Coefficient of Determination (CD) between a mean reference spectrum from a homogeneous batch and the NIR spectra that are recorded during the blending operation. Four formulations of commercial products were selected from different scales–including low dosage solid form-to show the usefulness of the method. In addition, this analytical procedure is tested with data from two different types of spectrometers (diode array instruments). Method calibration was performed with five batches (representing expected process variability) for each product: one for the computation of the homogeneous batch target spectrum and four to compute the limit of the CD values related to anticipated and acceptable homogeneity. Method validation was performed with homogeneous batches and with challenge spectra for assessing the specificity of the method. Real-world examples (e.g. technical, validation batches and clinical batches) were presented in order to demonstrate that this method is able to detect inhomogeneous batches. The new qualitative method presented in this paper is useful for determination of the blending endpoint, in assessing the blend uniformity in real-time and in increasing process understanding during early development and troubleshooting. Graphical Abstract

查看原文本刊更多论文

近红外光谱用于混合均匀性监测:基于确定系数的创新定性应用

混合工艺是制药工业固体剂型生产中的一个关键单元操作。近红外(NIR)光谱是实时评估混合均匀性的有力分析工具。本文提出了一种用于混合过程监控和终点确定的新方法。定量程序验证和NIR程序的维护是耗时的活动，可能会阻碍PAT工具在制药行业的采用。显然，行业需要更简单、更直观、易于构建、验证和维护的定性混合监测分析程序。本文介绍的方法包括跟踪均匀批次的平均参考光谱与混合过程中记录的近红外光谱之间的决定系数(CD)的趋势。选择了四种不同规模的商业产品配方，包括低剂量固体制剂，以表明该方法的有效性。此外，该分析过程用两种不同类型的光谱仪(二极管阵列仪器)的数据进行了测试。对每个产品进行了5个批次(代表预期的过程可变性)的方法校准:一个用于计算均匀批次的目标光谱，四个用于计算与预期和可接受的均匀性相关的CD值的限值。采用均质批和激发光谱进行方法验证，以评估该方法的特异性。为了证明该方法能够检测不均匀批次，给出了实际例子(如技术、验证批次和临床批次)。本文提出的新的定性方法有助于确定混合终点，实时评估混合均匀性，并在早期开发和故障排除中增加对工艺的理解。图形抽象

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.