Heinrich-Heine-University Düsseldorf, Institute of Pharmaceutics and Biopharmaceutics, Düsseldorf, Germany; NextPharma Waltrop, Pharbil Waltrop GmbH, Waltrop, Germany.
Christian-Albrechts-University Kiel, Institute of Electrical Engineering and Information Technology, Kiel, Germany.
Anal Chim Acta. 2017 Apr 8;961:119-127. doi: 10.1016/j.aca.2017.01.021. Epub 2017 Jan 25.
Microwave sensor systems using resonance technology at a single resonance in the range of 2-3 GHz have been shown to be a rapid and reliable tool for moisture determination in solid materials including pharmaceutical granules. So far, their application is limited to lower moisture ranges or limitations above certain moisture contents had to be accepted. Aim of the present study was to develop a novel multi-resonance sensor system in order to expand the measurement range. Therefore, a novel sensor using additional resonances over a wide frequency band was designed and used to investigate inherent limitations of first generation sensor systems and material-related limits. Using granule samples with different moisture contents, an experimental protocol for calibration and validation of the method was established. Pursuant to this protocol, a multiple linear regression (MLR) prediction model built by correlating microwave moisture values to the moisture determined by Karl Fischer titration was chosen and rated using conventional criteria such as coefficient of determination (R) and root mean square error of calibration (RMSEC). Using different operators, different analysis dates and different ambient conditions the method was fully validated following the guidance of ICH Q2(R1). The study clearly showed explanations for measurement uncertainties of first generation sensor systems which confirmed the approach to overcome these by using additional resonances. The established prediction model could be validated in the range of 7.6-19.6%, demonstrating its fit for its future purpose, the moisture content determination during wet granulations.
利用 2-3GHz 范围内单一共振的谐振技术的微波传感器系统已被证明是一种快速可靠的工具，可用于测定包括药物颗粒在内的固体材料中的水分。到目前为止，它们的应用仅限于较低的水分范围，或者必须接受超过一定水分含量的限制。本研究的目的是开发一种新型的多共振传感器系统，以扩大测量范围。因此，设计了一种使用附加共振的新型传感器，以研究第一代传感器系统的固有限制和材料相关限制。使用具有不同水分含量的颗粒样品，建立了用于校准和验证该方法的实验方案。根据该方案，通过将微波水分值与卡尔费休滴定法确定的水分值相关联，选择并使用传统标准（如决定系数（R）和校准均方根误差（RMSEC））对构建的多元线性回归（MLR）预测模型进行了评分。使用不同的运算符、不同的分析日期和不同的环境条件，根据 ICH Q2（R1）的指导对该方法进行了全面验证。该研究清楚地解释了第一代传感器系统测量不确定度的原因，这证实了通过使用附加共振来克服这些问题的方法。所建立的预测模型可以在 7.6-19.6%的范围内进行验证，表明其适合未来的用途，即在湿法制粒过程中测定水分含量。
