Emteborg Håkan, Charoud-Got Jean, Seghers John
European Commission, Joint Research Centre (JRC), Retieseweg 111, 2440 Geel, Belgium.
Pharmaceutics. 2022 May 7;14(5):1007. doi: 10.3390/pharmaceutics14051007.
The coupling of an infrared (IR) camera to a freeze dryer for monitoring of the temperature of a pharmaceutical formulation (sucrose/mannitol solution, 4:1%, /) during freeze-drying has been exploited further. The new development allows monitoring of temperatures simultaneously at the surface as well as vertically, (e.g., in depth) along the side using custom-made cuvettes. The IR camera was placed on the chamber roof of a process-scale freeze dryer. Monitoring of cuvettes containing the formulation took place from above where one side of each cuvette was equipped with a germanium window. The Ge-window was placed next to an IR mirror having a 45° angle. The long-wave infrared radiation (LWIR) coming from the inside of the cuvette was reflected upwards toward the IR camera. Accurate recording of the temperature along the cuvettes' depth profile was therefore possible. Direct imaging from -40 °C to 30 °C took place every 60 s on the surface and on the side with a 2 × 2 mm resolution per IR pixel for 45 h resulting in 2700 thermograms. Results are presented for freeze-drying of a pharmaceutical formulation as a function of time and spatially for the entire side (depth) of the cuvette. As the sublimation process was progressing, the spatial resolution (84 IR pixels for the side-view and 64 pixels for the surface-view) was more than sufficient to reveal lower temperatures deeper down in the material. The results show that the pharmaceutical formulation (a true solution at the onset) dries irregularly and that the sublimation front does not progress evenly through the material. During secondary drying, potential evaporative cooling of upper layers could be detected thanks to the high thermal and spatial resolution.
红外（IR）相机与冷冻干燥机耦合，用于监测药物制剂（蔗糖/甘露醇溶液，4:1%，/）冷冻干燥过程中的温度，这一应用得到了进一步拓展。新的进展使得能够使用定制比色皿同时监测表面温度以及沿侧面垂直方向（例如深度方向）的温度。红外相机安装在工业规模冷冻干燥机的腔室顶部。从上方对装有制剂的比色皿进行监测，每个比色皿的一侧配备有锗窗。锗窗放置在一个呈45°角的红外镜旁边。来自比色皿内部的长波红外辐射（LWIR）向上反射至红外相机。因此能够准确记录沿比色皿深度剖面的温度。在45小时内，每隔60秒对表面和侧面进行一次从-40°C到30°C的直接成像，每个红外像素的分辨率为2×2毫米，共得到2700张热成像图。给出了药物制剂冷冻干燥过程中温度随时间以及比色皿整个侧面（深度）空间变化的结果。随着升华过程的推进，空间分辨率（侧视图84个红外像素，表面视图64个像素）足以揭示物料中更深位置的较低温度。结果表明，药物制剂（开始时为真溶液）干燥不均匀，升华前沿在物料中推进不均匀。在二次干燥过程中，由于高的热分辨率和空间分辨率，能够检测到上层潜在的蒸发冷却现象。
