Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Universitaetstrasse 1, 40225 Duesseldorf, Germany.
Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Universitaetstrasse 1, 40225 Duesseldorf, Germany.
Eur J Pharm Biopharm. 2019 Apr;137:77-85. doi: 10.1016/j.ejpb.2019.02.015. Epub 2019 Feb 19.
In a previous publication, the development of an in-line Raman spectroscopic method for continuous API quantification during twin-screw wet granulation was presented. An in-line method was developed successfully and the developed method showed an acceptable prediction error. A disadvantage of the developed method was that a measurement was only possible in the dark since light influenced the Raman spectra and made a data interpretation impossible. Therefore, the measurement setup for the implementation of the Raman probe was optimised in the present study to allow a measurement in interior light and to further improve the predictive performance. With the optimised setup, two different calibration models were developed and compared. For the first calibration model, spectra were collected in the dark as before and for the second in interior light. The dark calibration model was able to predict the API content with an RMSEP of 0.31% and the light model with an RMSEP of 0.29%. Thus, both PLS models showed prediction errors in the same order. Consequently, it was possible to evaluate Raman spectra which were collected in interior light. Further, the previous prediction error of 0.60% could be clearly decreased. The optimised Raman method was applicable to evaluate the mixing efficiency of the twin-screw granulator during a split feeding process. The quality of the mixture was monitored behind different barrel sections by Raman spectroscopy and the corresponding API concentrations were predicted by the developed calibration model. For a screw length of 40 D and a screw configuration with two kneading blocks a good mixing ability was observed. For a screw length of 20 D and one kneading block the mixing efficiency was largely acceptable whereas a broad scattering of the API content was observed when no kneading blocks were used. In a second part, an experimental design was performed for each screw configuration to evaluate the influence of the barrel-fill level and screw speed on the mixing efficiency. The quality of the mixture using the entire barrel length was minimally influenced by the fill-level. For the other two positions, the screw speed influenced the quality of the mixture slightly. Thus, for an appropriate mixing, a certain barrel length and a screw configuration with two kneading blocks were necessary.
在之前的一篇出版物中，介绍了一种在线拉曼光谱法，用于在双螺杆湿法造粒过程中连续定量分析 API。成功开发了一种在线方法，该方法显示出可接受的预测误差。该方法的一个缺点是只能在黑暗中进行测量，因为光线会影响拉曼光谱，从而无法进行数据解释。因此，本研究对拉曼探头的测量设置进行了优化，以允许在室内光下进行测量，并进一步提高预测性能。使用优化的设置，开发并比较了两种不同的校准模型。对于第一个校准模型，如前所述，在黑暗中收集光谱，对于第二个模型，在室内光下收集光谱。暗模型能够以 0.31%的 RMSEP 预测 API 含量，而光模型则以 0.29%的 RMSEP 预测。因此，这两个 PLS 模型都显示出相同的预测误差。因此，可以评估在室内光下收集的拉曼光谱。此外，以前的预测误差 0.60%可以明显降低。优化后的拉曼方法可用于评估在分段进料过程中双螺杆造粒机的混合效率。通过拉曼光谱监测不同桶段的混合物质量，并通过开发的校准模型预测相应的 API 浓度。对于 40D 的螺杆长度和带有两个捏合块的螺杆配置，观察到良好的混合能力。对于 20D 的螺杆长度和一个捏合块，混合效率基本可以接受，而当不使用捏合块时，API 含量的分布很广。在第二部分，针对每种螺杆配置进行了实验设计，以评估桶填充水平和螺杆速度对混合效率的影响。使用整个桶长的混合物质量受填充水平的影响最小。对于其他两个位置，螺杆速度对混合物质量的影响很小。因此，为了达到适当的混合效果，需要一定的桶长和带有两个捏合块的螺杆配置。
