结晶是制造药物成分的重要一步。现在，FDA鼓励使用现代工艺分析技术（PAT）在药品生产和质量控制中。因此，该行业正在从经验转向以科学为基础的制造控制标准。亚博老虎机网登录结果，新技术正在进入制药行业的制造业。
Process Analytical Technologies are used for the analysis and control of manufacturing processes to assure an acceptable quality at the completion of the process. This is based on measuring critical quality parameters and performance attributes of raw and in-process materials and processes. The crystallization process is one of these. It requires the mixture and conditions to be tightly controlled in order to precipitate the correct crystalline form. An example of this, was at one of the world’s leading pharmaceutical companies, which had the requirement to tightly control the water content in an IPA/drug mixture in a glass-lined reactor such that the water content was just above 2.5%.
实验
Bruker Optics supplied aMATRIX-F fiber optic-based process Fourier transform NIR spectrometerand two 100-m lengths of low OH fused silica fiber optic cable along with a custom designed transmission probe contained in a 2-m hastelloy C22 DIP Pipe. The DIP pipe was needed for the glass-line reactor because no side ports were available for a standard probe. The DIP pipe was designed to enter the reactor through a flange at the top. The design and realization of this DIP pipe was done by a team of engineers using a sophisticated Computer Aided Design software to optimize the product. The initial calibration development was done in a pilot plant and then transferred to the reactor once the MATRIX-F had been installed. Spectra (32 scans, of roughly 15 s, at a resolution of 8 cm-1) were measured constantly over several batches. The spectra collected throughout the process, with different water contents are shown in Figure 1.
.jpg)
Figure 1.FT-NIR absorption spectra of the pilot plant mixture collected throughout the course of the reaction. Significant differences can be clearly observed. They are correlated to changes in the water content.
收集时间盖章的样品并在与适当的时间盖在线NIR频谱相关联之前，将其分析并在离线分析。水含量所得的校准模型如图2所示，其中预测准确性在1.9-3.7％的水含量范围内达到了0.02％。
.jpg)
Figure 2.用于预测水含量的基于PLS的模型的交叉验证结果。数据显示非常高的相关系数（99.76）和低误差（0.02绝对）。
定量分析
Near-infrared spectra result from combination and overtone bands of C-H, N-H, O-H, etc. vibrations. Since most reaction mixtures contain some organic components with these bonds, they are ideal for near-infrared analysis. The OPUS/QUANT quantitative analysis software package uses partial lease squares (PLS) to develop quantitative models. Typically, the development of a model requires measuring samples that contain a range of concentrations of the components of interest. The unique Quant self-optimisation routine is then applied to develop the calibration model. In this example, NIR spectra of the reaction mixture were constantly collected in a pilot plant and correlated through their time stamp to samples pulled from the reactor and then analyzed off-line.
Measurement Options
Bruker Optics提供了各种仪器，可满足所有特定需求。对于过程应用程序MATRIX-F由于其多重能力，坚固性和易于可用性，因此建议使用。可以在线和在线测量液体，固体和浆液的多种过程测量配件。
矩阵-F也可以通过添加简单的纤维耦合小瓶固定器并使用一次性玻璃小瓶来使用。这可能是在上线之前开发校准模型的替代解决方案。可以使用在线流动池或传输探针直接从液体流中收集近红外光谱，而没有样品制备。光纤的使用使得可以将仪器定位在远处的控制室或围栏中，在靠近测量地点的危险位置。高质量的光谱通常可以在不到一分钟的时间内收集，并且对多个组件的定量分析很容易执行。所有这些因素使NIR光谱成为监视过程的快速，可靠的在线工具。
.jpg)
Figure 3.矩阵-F单独封闭的模块，旨在轻松适合标准的19英寸架子和外壳。该实验的光谱仪与触摸屏计算机一起将其安装在距离样品点100 m的环境外壳中。结果通过4-20 MA接口传输到过程控制系统，并且水含量由基于NIR结果的封闭环控制。Bruker Optics不断改善其产品，并保留更改规格的权利，恕不另行通知。
Implementation
In a process environment theMATRIX-Fcan be used, along with the process software ADIO, to measure and analyze the sample and send the results to a DCS through a variety of I/O options such as 4-20 mA, Modbus, Profibus, Industrial Ethernet, etc.
.jpg)
This information has been sourced, reviewed and adapted from materials provided by Bruker Optics.
For more information on this source, please visitBruker Optics。