Mayeresse Y, Veillon R, Sibille P H, Nomine C
Freeze-drying, Industrialization, GlaxoSmithKline Biologicals, Rue de l'Institut, 89, 1330 Rixensart, Belgium.
PDA J Pharm Sci Technol. 2007 May-Jun;61(3):160-74.
A cold plasma ionization device has been designed to monitor freeze-drying processes in situ by monitoring lyophilization chamber moisture content. This plasma device, which consists of a probe that can be mounted directly on the lyophilization chamber, depends upon the ionization of nitrogen and water molecules using a radiofrequency generator and spectrometric signal collection. The study performed on this probe shows that it is steam sterilizable, simple to integrate, reproducible, and sensitive. The limitations include suitable positioning in the lyophilization chamber, calibration, and signal integration. Sensitivity was evaluated in relation to the quantity of vials and the probe positioning, and correlation with existing methods, such as microbalance, was established. These tests verified signal reproducibility through three freeze-drying cycles. Scaling-up studies demonstrated a similar product signature for the same product using pilot-scale and larger-scale equipment. On an industrial scale, the method efficiently monitored the freeze-drying cycle, but in a larger industrial freeze-dryer the signal was slightly modified. This was mainly due to the positioning of the plasma device, in relation to the vapor flow pathway, which is not necessarily homogeneous within the freeze-drying chamber. The plasma tool is a relevant method for monitoring freeze-drying processes and may in the future allow the verification of current thermodynamic freeze-drying models. This plasma technique may ultimately represent a process analytical technology (PAT) approach for the freeze-drying process.
一种冷等离子体电离装置被设计用于通过监测冻干腔室的水分含量来原位监测冻干过程。这种等离子体装置由一个可直接安装在冻干腔室上的探头组成，它依靠射频发生器和光谱信号采集来实现氮气和水分子的电离。对该探头进行的研究表明，它可进行蒸汽灭菌、易于集成、具有可重复性且灵敏度高。其局限性包括在冻干腔室内的合适定位、校准以及信号整合。针对小瓶数量和探头定位评估了灵敏度，并建立了与现有方法（如微量天平）的相关性。这些测试通过三个冻干循环验证了信号的可重复性。放大研究表明，使用中试规模和更大规模的设备，同一产品具有相似的产品特征。在工业规模上，该方法有效地监测了冻干循环，但在更大的工业冻干机中，信号略有改变。这主要是由于等离子体装置相对于蒸汽流动路径的定位，而冻干腔内蒸汽流动路径不一定均匀。等离子体工具是监测冻干过程的一种相关方法，未来可能有助于验证当前的热力学冻干模型。这种等离子体技术最终可能代表一种用于冻干过程的过程分析技术（PAT）方法。
