Coriolis Pharma Research GmbH, Fraunhoferstrasse 18 b, 82152 Martinsried, Germany; Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Butenandtstrasse 5, Ludwig-Maximilians-Universitaet München, D-81377 Munich, Germany.
Coriolis Pharma Research GmbH, Fraunhoferstrasse 18 b, 82152 Martinsried, Germany.
Int J Pharm. 2023 Aug 25;643:123285. doi: 10.1016/j.ijpharm.2023.123285. Epub 2023 Jul 31.
High-concentration protein formulations (HCPFs) represent a common strategy and freeze-drying can mitigate the stability challenges of HCPFs. In general, an in-depth characterization of the lyophilization process is essential to not impair the product quality by inappropriate process parameters. The aim of this study was to create a primary drying design space for lyophilized HCPFs by utilizing the heat flux sensor (HFS) integrated in a MicroFD with a minimum number of cycles and product vials. All the necessary data to obtain the design space were determined starting from only two lyophilization cycles, each holding 19 vials. The vial heat transfer coefficient (Kv) was determined by the HFS and compared to gravimetric values. The results indicate a consistant offset between the HFS and the gravimetry based values for annealed samples with higher protein content. This work highlights a possibility of integrating new technologies, the HFS and the MicroFD to generate a design space for lyophilization of HCPFs, which enables to implement a QbD approach at minimal material and time investment.
高浓度蛋白质制剂（HCPFs）是一种常见的策略，冷冻干燥可以减轻 HCPFs 的稳定性挑战。通常，深入了解冻干过程对于避免因不适当的工艺参数而损害产品质量至关重要。本研究旨在通过使用集成在 MicroFD 中的热流传感器（HFS）和最小数量的循环和产品小瓶，为冻干 HCPFs 创建一个主干燥设计空间。从仅两个冻干循环开始，每个循环包含 19 个小瓶，就可以确定获得设计空间所需的所有数据。通过 HFS 确定小瓶传热系数（Kv），并与重量法值进行比较。结果表明，对于退火样品，具有较高蛋白质含量的 HFS 和基于重量法的值之间存在一致的偏移。这项工作强调了集成新技术（HFS 和 MicroFD）以生成 HCPFs 冻干设计空间的可能性，这使得可以在最小的材料和时间投资下实施 QbD 方法。
