Fonteyne Margot, Arruabarrena Julen, de Beer Jacques, Hellings Mario, Van Den Kerkhof Tom, Burggraeve Anneleen, Vervaet Chris, Remon Jean Paul, De Beer Thomas
Laboratory of Pharmaceutical PAT, Ghent University, Harelbekestraat 72, Ghent, Belgium.
Department of Chemistry, Universitat Autònoma de Barcelona, UAB, Barcelona, Spain.
J Pharm Biomed Anal. 2014 Nov;100:21-27. doi: 10.1016/j.jpba.2014.07.012. Epub 2014 Jul 27.
This study focuses on the thorough validation of an in-line NIR based moisture quantification method in the six-segmented fluid bed dryer of a continuous from-powder-to-tablet manufacturing line (ConsiGma™ 25, GEA Pharma Systems nv, Wommelgem, Belgium). The moisture assessment ability of an FT-NIR spectrometer (Matrix™-F Duplex, Bruker Optics Ltd, UK) equipped with a fiber-optic Lighthouse Probe™ (LHP, GEA Pharma Systems nv, Wommelgem, Belgium) was investigated. Although NIR spectroscopy is a widely used technique for in-process moisture determination, a minority of NIR spectroscopy methods is thoroughly validated. A moisture quantification PLS model was developed. Twenty calibration experiments were conducted, during which spectra were collected at-line and then regressed versus the corresponding residual moisture values obtained via Karl Fischer measurements. The developed NIR moisture quantification model was then validated by calculating the accuracy profiles on the basis of the analysis results of independent in-line validation experiments. Furthermore, as the aim of the NIR method is to replace the destructive, time-consuming Karl Fischer titration, it was statistically demonstrated that the new NIR method performs at least as good as the Karl Fischer reference method.
本研究着重对连续的从粉末到片剂生产线（ConsiGma™ 25，GEA制药系统公司，比利时沃梅尔赫姆）的六段式流化床干燥器中基于近红外（NIR）的在线水分定量方法进行全面验证。研究了配备光纤灯塔探头（LHP，GEA制药系统公司，比利时沃梅尔赫姆）的傅里叶变换近红外（FT-NIR）光谱仪（Matrix™-F Duplex，英国布鲁克光学有限公司）的水分评估能力。尽管近红外光谱法是一种广泛用于过程中水分测定的技术，但少数近红外光谱法经过了全面验证。开发了一种水分定量偏最小二乘法（PLS）模型。进行了20次校准实验，在此期间在线采集光谱，然后将其与通过卡尔费休测量获得的相应残余水分值进行回归分析。然后，根据独立在线验证实验的分析结果计算准确度分布图，对所开发的近红外水分定量模型进行验证。此外，由于近红外方法的目的是取代具有破坏性且耗时的卡尔费休滴定法，经统计证明，新的近红外方法的性能至少与卡尔费休参考方法一样好。
