Kawasaki Hidenori, Shimanouchi Toshinori, Takahashi Kanako, Kimura Yukitaka
Graduate School of Environmental and Life Science, Okayama University.
Formulation R&D Center, CMC R&D Division, Shionogi & Co., Ltd.
Chem Pharm Bull (Tokyo). 2018;66(12):1122-1130. doi: 10.1248/cpb.c18-00494.
The freezing stage cannot be directly controlled, which leads to variation in product quality and low productivity during the lyophilization process. Our objective was to establish a robust design space for the primary drying stage using ice nucleation control based on the pressurization and depressurization technique. We evaluated the specific surface area (SSA), water content, scanning electron microscopy (SEM) images, and water vapor transfer resistance of the dried layer (R) of the products. The ice nucleation control resulted in a reduction of the SSA value and in an increase in water content. SEM observation suggested that the ice nucleation control enabled formation of large ice crystals, which was consistent with the reduction in the R value. As a result, the generation of collapsed cakes was inhibited, whereas 18% of the collapsed cakes were observed without ice nucleation control. Finally, this technique succeeded in determining a robust design space for the primary drying stage to produce uniform products of higher productivity. It was considered, from the present findings, that controlling the formation of large ice crystals impacted the product quality and productivity.
冷冻阶段无法直接控制，这导致冻干过程中产品质量出现波动且生产率较低。我们的目标是基于增压和减压技术，通过冰核控制为一次干燥阶段建立一个稳健的设计空间。我们评估了产品的比表面积（SSA）、含水量、扫描电子显微镜（SEM）图像以及干燥层的水蒸气传递阻力（R）。冰核控制导致SSA值降低且含水量增加。SEM观察表明，冰核控制能够形成大冰晶，这与R值的降低相一致。结果，抑制了塌陷饼块的产生，而在没有冰核控制的情况下观察到18%的塌陷饼块。最后，该技术成功地为一次干燥阶段确定了一个稳健的设计空间，以生产出生产率更高且质量均匀的产品。从目前的研究结果来看，控制大冰晶的形成对产品质量和生产率有影响。
