GlaxoSmithKline, Collegeville, Pennsylvania 19426.
Mettler-Toledo, Columbia, Maryland 21046.
J Pharm Sci. 2011 Aug;100(8):3431-3440. doi: 10.1002/jps.22556. Epub 2011 Mar 30.
Application of process analytical technology in the pharmaceutical industry has led to a great number of studies into inline instrumentation. Near-infrared moisture monitoring in fluid bed drying and content uniformity assurance in blending are gaining acceptance for monitoring and quality control of these processes. Although these techniques are a great improvement over traditional methods, each is performed at points in processing wherein processing is well understood and interfacing equipment is relatively easy. More complex unit operations have largely been unexplored due to complexities interfacing inline analytical equipment to unit operations or a lack of methodologies that can be applied to measure attributes of interest. This paper reports results from a study utilizing a focused beam reflectance measurement system equipped with window scraper technology for the inline measurement and control of a high shear wet granulation (HSWG) process. In addition to this, offline results obtained with a particle vision microscope system are compared to verify the results obtained inline. It is shown that using these technologies in monitoring the HSWG process greatly increases process understanding of physical changes occurring during processing through real-time observation of particle size, leading to real-time control of the process.
在制药行业中，过程分析技术的应用导致了大量关于在线仪器的研究。近红外水分监测在流化床干燥和混合内容均匀性保证方面正在被接受，用于监测和质量控制这些过程。虽然这些技术比传统方法有了很大的改进，但每种方法都是在处理过程中进行的，在这些过程中，处理过程已经被很好地理解，并且接口设备相对容易。由于将在线分析设备与单元操作接口的复杂性，或者缺乏可用于测量感兴趣属性的方法，更复杂的单元操作在很大程度上仍未得到探索。本文报告了一项利用聚焦光束反射测量系统和带有刮窗技术的研究结果，用于在线测量和控制高剪切湿法制粒（HSWG）过程。此外，还比较了使用粒子视觉显微镜系统获得的离线结果，以验证在线获得的结果。结果表明，通过实时观察粒径，使用这些技术在线监测 HSWG 过程大大提高了对加工过程中发生的物理变化的过程理解，从而实现了对过程的实时控制。
