Heinrich-Heine-University Düsseldorf, Institute of Pharmaceutics and Biopharmaceutics, Universitätsstr. 1, 40225 Düsseldorf, Germany.
L.B. Bohle Maschinen + Verfahren GmbH, Industriestr. 18, 59320 Ennigerloh, Germany.
Int J Pharm. 2018 Feb 15;537(1-2):193-201. doi: 10.1016/j.ijpharm.2017.12.040. Epub 2017 Dec 27.
The trend towards continuous manufacturing in the pharmaceutical industry is associated with an increasing demand for advanced control strategies. It is a mandatory requirement to obtain reliable real-time information on critical quality attributes (CQA) during every process step as the decision on diversion of material needs to be performed fast and automatically. Where possible, production equipment should provide redundant systems for in-process control (IPC) measurements to ensure continuous process monitoring even if one of the systems is not available. In this paper, two methods for real-time monitoring of granule moisture in a semi-continuous fluid-bed drying unit are compared. While near-infrared (NIR) spectroscopy has already proven to be a suitable process analytical technology (PAT) tool for moisture measurements in fluid-bed applications, microwave resonance technology (MRT) showed difficulties to monitor moistures above 8% until recently. The results indicate, that the newly developed MRT sensor operating at four resonances is capable to compete with NIR spectroscopy. While NIR spectra were preprocessed by mean centering and first derivative before application of partial least squares (PLS) regression to build predictive models (RMSEP = 0.20%), microwave moisture values of two resonances sufficed to build a statistically close multiple linear regression (MLR) model (RMSEP = 0.07%) for moisture prediction. Thereby, it could be verified that moisture monitoring by MRT sensor systems could be a valuable alternative to NIR spectroscopy or could be used as a redundant system providing great ease of application.
制药行业向连续化制造发展的趋势，对先进的控制策略提出了更高的要求。在每个工艺步骤中，都需要可靠的实时关键质量属性（CQA）信息，以便能够快速、自动地决定是否放行物料，这已经成为强制性要求。在可能的情况下，生产设备应为过程控制（IPC）测量提供冗余系统，以确保即使其中一个系统不可用，也能持续监测过程。本文比较了两种用于半连续流化床干燥器中颗粒水分实时监测的方法。近红外（NIR）光谱法已被证明是流化床应用中水分测量的合适过程分析技术（PAT）工具，而微波谐振技术（MRT）直到最近才显示出难以监测 8%以上水分的能力。结果表明，新开发的在四个谐振点工作的 MRT 传感器能够与 NIR 光谱法相媲美。在将偏最小二乘（PLS）回归应用于预测模型（RMSEP=0.20%）之前，NIR 光谱通过均值中心化和一阶导数进行预处理，而两个谐振点的微波水分值足以建立一个统计学上非常接近的多元线性回归（MLR）模型（RMSEP=0.07%）用于水分预测。因此，可以验证 MRT 传感器系统的水分监测可以作为 NIR 光谱法的有价值替代品，或者可以作为提供极大易用性的冗余系统使用。
