Fonteyne Margot, Gildemyn Delphine, Peeters Elisabeth, Mortier Séverine Thérèse F C, Vercruysse Jurgen, Gernaey Krist V, Vervaet Chris, Remon Jean Paul, Nopens Ingmar, De Beer Thomas
Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium.
Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium.
Eur J Pharm Biopharm. 2014 Aug;87(3):616-28. doi: 10.1016/j.ejpb.2014.02.015. Epub 2014 Mar 5.
Classically, the end point detection during fluid bed drying has been performed using indirect parameters, such as the product temperature or the humidity of the outlet drying air. This paper aims at comparing those classic methods to both in-line moisture and solid-state determination by means of Process Analytical Technology (PAT) tools (Raman and NIR spectroscopy) and a mass balance approach. The six-segmented fluid bed drying system being part of a fully continuous from-powder-to-tablet production line (ConsiGma™-25) was used for this study. A theophylline:lactose:PVP (30:67.5:2.5) blend was chosen as model formulation. For the development of the NIR-based moisture determination model, 15 calibration experiments in the fluid bed dryer were performed. Six test experiments were conducted afterwards, and the product was monitored in-line with NIR and Raman spectroscopy during drying. The results (drying endpoint and residual moisture) obtained via the NIR-based moisture determination model, the classical approach by means of indirect parameters and the mass balance model were then compared. Our conclusion is that the PAT-based method is most suited for use in a production set-up. Secondly, the different size fractions of the dried granules obtained during different experiments (fines, yield and oversized granules) were compared separately, revealing differences in both solid state of theophylline and moisture content between the different granule size fractions.
传统上，流化床干燥过程中的终点检测是使用间接参数进行的，例如产品温度或出口干燥空气的湿度。本文旨在将这些经典方法与通过过程分析技术（PAT）工具（拉曼光谱和近红外光谱）以及质量平衡方法进行的在线水分和固态测定进行比较。本研究使用了作为从粉末到片剂全连续生产线（ConsiGma™-25）一部分的六段式流化床干燥系统。选择茶碱：乳糖：聚乙烯吡咯烷酮（30:67.5:2.5）混合物作为模型配方。为了开发基于近红外的水分测定模型，在流化床干燥器中进行了15次校准实验。之后进行了6次测试实验，在干燥过程中使用近红外光谱和拉曼光谱对产品进行在线监测。然后比较了通过基于近红外的水分测定模型、基于间接参数的经典方法和质量平衡模型获得的结果（干燥终点和残留水分）。我们的结论是，基于PAT的方法最适合用于生产设置。其次，分别比较了在不同实验中获得的干燥颗粒的不同粒度级分（细粉、收率和超大颗粒），揭示了不同粒度级分之间茶碱的固态和水分含量的差异。
