Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium.
Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
Int J Pharm. 2019 Jun 30;565:358-366. doi: 10.1016/j.ijpharm.2019.05.006. Epub 2019 May 7.
In the current study, the ability to use in-line NIR inside the feed frame of a tablet press to monitor the residence time distribution inside the tablet press was investigated. Pulse-response experiments were performed. In-line measurements inside the feed frame were compared to measurements on the actual produced tablets and the influence of different tableting parameters on the concentration profiles were studied. Turret speed had a major influence on the concentration profiles and RTD parameters. The in-line and off-line concentration profiles did not align with each other as spiking material was still detected in the tablets when no spiking material was observed in the powder blend by the in-line measuring method. The cause of this mismatch between the in-line and off-line curves was the in-line measuring position. By adjusting the position of the NIR probe to the bottom of the feed frame instead of at the top of the feed frame, a perfect alignment between in-line and off-line concentration curves was acquired. In-line measurements at the bottom of the feed frame could, if optimisation to avoid probe fouling is possible, be ideal for real-time measurement and control of the blend concentration during tableting. When probe fouling cannot be avoided, the correlation between the in-line measured concentration at the top of the feed frame and the concentration of the produced tablets should be investigated and modelled to enable real-time measurement and control based on in-line measurements.
在本研究中，研究了在压片机料斗内使用在线近红外（NIR）监测压片机内停留时间分布的能力。进行了脉冲响应实验。将料斗内的在线测量结果与实际生产的片剂进行了比较，并研究了不同压片参数对浓度分布的影响。转塔速度对浓度分布和 RTD 参数有重大影响。在线和离线浓度分布不一致，因为当在线测量方法在粉末混合物中未观察到加标材料时，仍在片剂中检测到加标材料。在线和离线曲线之间不匹配的原因是在线测量位置。通过将 NIR 探头的位置调整到料斗的底部而不是顶部，可以实现在线和离线浓度曲线之间的完美对齐。如果可以优化以避免探头堵塞，那么在料斗底部进行在线测量可能是压片过程中实时测量和控制混合物浓度的理想选择。当无法避免探头堵塞时，应研究和建模在线测量顶部测量的浓度与生产片剂浓度之间的相关性，以便能够基于在线测量进行实时测量和控制。
