Coriolis Pharma Research GmbH, D-82152 Planegg, Germany; Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig Maximilian University, D-81377 Munich, Germany.
Coriolis Pharma Research GmbH, D-82152 Planegg, Germany.
Eur J Pharm Biopharm. 2020 Aug;153:84-94. doi: 10.1016/j.ejpb.2020.05.028. Epub 2020 Jun 1.
Freeze-drying methodology requires an in-depth understanding and characterization for optimal processing of biopharmaceuticals. Particularly the primary drying phase, the longest and most expensive stage of the process, is of interest for optimization. The currently used process analytical technology (PAT) tools give highly valuable insights but come with limitations. Our study describes, for the first time, the application of a heat flux sensor (HFS) to build a primary drying design space and predict the process evolution. First, the heat transfer coefficient (K) generated by HFS and by the most accurate, but time-consuming and invasive, gravimetric method were compared. Second, the applicability to generate a design space was tested and verified. Obtained results revealed a good agreement of the values generated from this new and fast HFS compared to the gravimetric determination. Additionally, residual moisture assessed by Karl-Fischer titration and frequency modulated spectroscopy (FMS) support the quality of the obtained predictions. Thus, the HFS approach can substantially accelerate evaluation, development and transfer of a freeze-drying cycle.
冷冻干燥方法学需要深入的理解和特性描述，以实现生物制药的最佳处理。特别是在该过程中最长和最昂贵的阶段——初级干燥阶段，是优化的重点。目前使用的过程分析技术 (PAT) 工具提供了非常有价值的见解，但也存在局限性。我们的研究首次描述了应用热通量传感器 (HFS) 来构建初级干燥设计空间并预测工艺演变。首先，比较了 HFS 和最准确但耗时且具侵入性的重量法产生的传热系数 (K)。其次，测试和验证了生成设计空间的适用性。得到的结果表明，与重量法测定相比，这种新的快速 HFS 产生的值具有良好的一致性。此外，卡尔-费歇尔滴定和频率调制光谱 (FMS) 评估的残余水分支持了获得的预测的质量。因此，HFS 方法可以大大加快冷冻干燥周期的评估、开发和转移。
