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[生产设备] 走进近红外(一)

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药徒
发表于 2019-9-20 11:32:11 | 显示全部楼层 |阅读模式

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近红外光谱技术发展简述

近红外区域按ASTM(美国材料检测协会)定义是指波长在7802526nm范围内的电磁波山,是人们最早发现的非可见光区域,距今已有近200年历史。

本世纪初,人们采用摄谱的方法首次获得了有机化合物的近红外光谱,并对有关基团的光谱特征进行了解释,预示着近红外光谐( Near InfraredSpectroscopy,缩写为NIR )有可能作为分析技术的一种手段得到应用。

50年代以前,由于缺乏仪器基础,近红外光谱的研究只限于为数不多的几个实验室中,且没有得到实际应用。

50年代中后期,随着简易型近红外光谱仪器的出现及Norris等人在近红外光谱漫反射技术上所做的大量工作,掀起了近红外光谱应用的一个小高潮,近红外光谱在测定农副产品(包括谷物、饲料、水果、蔬菜、肉、蛋、奶等)的品质(如水分、蛋白、油脂含量等)方面得到广泛使用。

由于这些应用都基于传统的光谱定量方法,当样品的背景、颗粒度、基体等发生变化时,测量结果往往产生较大的误差了进人60年代中后期,随着(中)红外光谱技术的发展及其在化合物结构表征中所起的巨大作用,使人们谈漠了近红外光谱在分析测试中的应用。

在此后约20年的时间里,除在农副产品领域的传统应用之外,近红外光谱技术几乎处于徘徊不前的状态,以致被人们称其为光谱技术中的沉睡者。

进入80年代后期,近红外光谱才真正为人们所注意,这在很大程度上应归功于化学计量学方法的应用,再加上过去中红外光谱技术累积的经验,使近红外光谱分析技术迅速得到推广,成为一门独立的分析技术,有关近红外光谱技术迅速得到推广,成为一门独立的分析技术,有关近红外光谱的研究及应用文献几乎呈指数增长。

1983年以后,近红外光谱仪器的生产厂商就开始每年召开1次近红外光谱的国际会议,但会议内容较着重于其生产仪器的改进及应用。

1987举办第一届近红外光谱研究与应用的国际会议,至今已举办了9届。每次会议都出版了相应的文集,刊登了大量涉及近红外光谱仪器、计量学方法、新技术发展及各种新应用的文章。

1988,国际近红外光谱协会(CNIRS )成立,该协会北美分会对1905- 1990 年有关近红外光谱的文献做了全面汇编(CBIBL)。

关于近红外光谱研究及应用的专业期刊JoumalNearInfraredSpectroscopy和Near Infrared News 先后于90年代初创刊

同时,在其它涉及分析与光谱的杂志,如Applied Spectroscopy 、AnlticalChemistry上也刊登了大量近红外光谱基础研究及应用的十章。近年来,有很多近红外光谱技术也出现在各国的专利中。

我国对近红外光谱技术的研究及应用起步较晚,但1995年以来已受到了多方面的关注,并在仪器的研制、软件开发、基础研究和应用等方面取得了可喜的成果。尤其在石油化工领城中的应用已积累了一些实际经验,并有望得到一定的经济效益。


陆婉珍

女,上海市人,1924 年出生。

1946年毕业于中央大学化学工程系。

1949年就读于美国利诺州立大学,获化学硕士学位。

1951年就读于美国俄亥俄州立大学,获化学博士学位

1991年1月当选为中国科学院院士。

1995 年以来,致力于组织近红外光谱仪的研制,已开发出国产NIR-2000型近红外光谱仪,其中包括数据计算软件及近红外光谱法在石油产品分析中的模型,并在部分炼油中取得极受欢迎的成果。

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发表于 2019-9-20 11:52:15 | 显示全部楼层
期待继续更新
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药徒
 楼主| 发表于 2019-9-20 12:32:33 | 显示全部楼层

哈哈,谢谢关注,一起学习
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药生
发表于 2019-9-20 12:48:03 | 显示全部楼层
The Road to Real-Time Release: At-line NIR Testing
At-line NIR measurements can replace a laboratory HPLC measurement for API content.

Oral solid-dosage forms are commonly examined by time-consuming, off-line tests of only randomly chosen samples. This article discusses an alternative, fully integrated, at-line spectroscopic quality control approach for oral solid dosage forms and presents the findings of a case study in this field.

Benefits of PAT solutions
Process analytical technology (PAT) tools allow process monitoring and process control of the critical parameters during production. Furthermore, in many cases, PAT even provides a better process understanding.

PAT tools are mainly integrated as in-line, on-line, or at-line solutions. In-line and on-line techniques perform frequent measurements directly in the product stream, allowing fast reaction and even process control. The difference between these two solutions is how the PAT tool is integrated into the process; on-line uses a sampling loop while in-line refers to measurements directly in the process stream. These solutions are the methods of choice for detecting short process disturbances. Nevertheless, integration into the process and, in particular, the requirement to find a representative measurement position without disturbing the process, might be challenging.

For at-line PAT tools, the samples are commonly withdrawn out of the process, and the analysis is performed on the defined number of samples in the production environment. Several tests can be performed on exactly the same sample during the manufacturing process, such as measurement of weight and content needed for a content uniformity assay. Therefore, such a system is a good start for the definition of the real-time release (RTR) strategy. Furthermore, as the analysis is performed directly after the manufacturing step (not off-line in the lab), it enables the manufacturer to react immediately to process variations and reduce waste by potentially stopping the process and recapturing the powder.

Advantages of spectroscopic techniques
Spectroscopic techniques, such as near infrared (NIR) spectroscopy, are non-invasive, non-destructive, and allow fast quality control investigations on higher amounts of samples during the complete manufacturing process. Thus, NIR exhibits great potential as a PAT tool for control of the critical parameters during production and better process understanding. Furthermore, the same NIR measurement delivers information about chemical and physical attributes of the sample. Thus, it is applicable for measurement of API concentration, moisture, density of the sample, and so on.

Two major measurement approaches for NIR spectroscopy, transmission and reflection, are possible. Reflection is the method to choose on moving samples (e.g., powder, tablets) due to its ability to measure at high speed and its low sensitivity to changes in sample thicknesses. One limitation is that the penetration depth of the NIR light has to be taken into account, with a special focus on the ratio of measured volume to the whole sample volume.

For at-line measurement on a static sample, transmission is a better solution; because the light signal travels all the way through the sample (rather than partway through as in reflection NIR), the information within the sample is acquired. Additionally, measurement on static samples brings an advantage of longer possible measurement time, allowing the usage of slower NIR spectroscopy devices with higher resolution.

The combination of measured sample volume, non-moving sample, and higher resolution for transmission NIR allows measurement of lower API concentrations compared to reflection NIR. However, the thickness of the sample might be a limitation for transmission, because the light needs to propagate through the sample. Tablets less than 9 mm thick are usually accessible by transmission NIR.

At-line PAT solution
To benefit from all the advantages of an at-line spectroscopic PAT solution, the PAT tool should be integrated into the process to allow frequent measurement and control during the process. For example, in an at-line tablet tester, the tablets are automatically sampled after the tableting process and pass individual measurement positions (e.g., tablet weight measured by a scale and API content measured by NIR). Subsequently, these values are transferred back to the process control system. As mentioned, this position is a good choice for the NIR spectroscopy transmission measurement, although there are additional challenges for integration into the process. It is well known that an off-line NIR spectroscopy lab analysis in transmission is a precise and reliable technique, but the positioning has to be as precise as possible, because it influences the signal-to-noise ratio. Additionally, unwanted scatter light, which escapes from the sides of a sample (tablet), also has a high influence on the measurement precision and should be avoided. Therefore, new challenges for an automated at-line PAT solution are precise and repetitive positioning and avoiding scattered light when measuring during the process.

Two of the main goals of at-line analysis are to replace the final analysis in the lab (e.g., high-performance liquid chromatography [HPLC] for the API concentration and content uniformity) or the direct release of batches after production (i.e., RTR). At least four release tests (i.e., identity, assay, content uniformity, and even dissolution) performed by NIR in combination with a scale might be a part of the RTR strategy and thus replace these lab tests. The following case study performed by Bayer in collaboration with Kraemer Elektronik and Fette Compacting shows that this goal is achievable.


Case study
Bayer tested a technique using an automated tablet tester equipped with NIR spectroscopy on a formulation with a low API concentration. In this study, the suitability of an integrated at-line transmission NIR spectroscopy solution to predict the API concentration of the sample tablets with an accuracy comparable to HPLC was investigated.

Checkmaster
Figure 1: The NIR Checkmaster (Kraemer Elektronik / Fette Compacting) is an automated tablet tester. Figures are courtesy of the author.
Methods. Tablets were produced on a rotary tablet press (2200i, Fette Compacting) with 6-mm round concave punches. The compression force and compression speed were varied to verify the robustness of the model. Tablets with eight different API concentration ratios (in the range of 0–6% API concentration) were compressed. Thereafter, the tablets were randomly assigned to either a calibration or a test set.

Subsequently, the calibration set tablets were measured with NIR Flex N-500 Solids Transmittance (Büchi Labortechnik). The calibration model was calculated with NIRCal Software (Büchi Labortechnik) and then transferred to the NIR Checkmaster (Fette Compacting/Kraemer Elektronik). The NIR Checkmaster, shown in Figure 1, is a fully automated tablet tester with a built-in NIR Flex N-500 Solids Transmittance spectrometer.

The tablets are withdrawn out of the process and guided by the sampling gate of the tablet press to the NIR Checkmaster. The NIR Checkmaster positions the tablets by the rotating star wheel in front of individual testing stations: weight, thickness, hardness, diameter, and NIR transmission measurement cell, where the measurements are performed. Thereafter, all measured values (including API content measured by NIR transmission) are transferred to the tablet press. The tablet press can take an action based on the results. Furthermore, these results are included into the batch record.  

The test set tablets with four different API concentration ratios were analyzed with the NIR Checkmaster, which was operated by the tablet press software. All tablets were measured with HPLC to determine the reference API concentration. Results of the NIR Checkmaster and HPLC were then compared.

Results and discussion. Figure 2 shows that the mean API HPLC values and the NIR Checkmaster values have comparable standard deviations for the four concentrations of the test set. The NIR Checkmaster values include manufacturing process variabilities, such as changes of the compression speed and the compression force. An exact positioning of the tablet using a patented format part tablet holder that always positions the tablet in the same way in front of the sensor was crucial for obtaining accurate results using the tablet tester. In addition, the holder avoids the occurrence of unwanted scatter light.

chart
Figure 2: Comparison of the API concentration predicted with NIR Checkmaster and API concentration values measured by high-performance liquid chromatography (HPLC). The error bars are visualizing the standard deviation.

Conclusion
Based on the results that are shown in Figure 2, the presented at-line spectroscopic solution exhibits a great potential for a robust RTR strategy, because the NIR Checkmaster is able to predict the same concentration values with a comparable standard deviation as HPLC. Additionally, the tablet tester is fully integrated into the process, enabling process control and documentation. This PAT solution already offers several benefits along the road to RTR: process control and reduction of waste batch production, gaining of process understanding and process knowledge, and finally reduction or elimination of the off-line lab analysis.

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在线NIR测量可以取代API内容的实验室HPLC测量。  详情 回复 发表于 2019-9-20 12:48
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药生
发表于 2019-9-20 12:48:44 | 显示全部楼层
gdg661837 发表于 2019-9-20 12:48
The Road to Real-Time Release: At-line NIR Testing
At-line NIR measurements can replace a laborator ...

在线NIR测量可以取代API内容的实验室HPLC测量。
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药徒
发表于 2019-9-20 13:31:22 | 显示全部楼层
gdg661837 发表于 2019-9-20 12:48
在线NIR测量可以取代API内容的实验室HPLC测量。

近红外技术还不是国家标准

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我说的是标题。  详情 回复 发表于 2019-9-20 14:21
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药徒
发表于 2019-9-20 13:31:48 | 显示全部楼层
了解了,谢谢lz。期待后续更新
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药生
发表于 2019-9-20 14:21:43 | 显示全部楼层
18963098278 发表于 2019-9-20 13:31
近红外技术还不是国家标准

我说的是标题。
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发表于 2019-9-20 15:59:20 | 显示全部楼层
红外现在每个公司使用度不多;但其作用非常大、也比较复杂。
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药士
发表于 2019-9-20 22:56:25 | 显示全部楼层
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