Yoon Kyu, Narsimhan Vivek
Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN 47907, USA.
Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN 47907, USA.
Int J Pharm. 2023 Mar 25;635:122746. doi: 10.1016/j.ijpharm.2023.122746. Epub 2023 Feb 20.
This study uses a heat flux sensor and temperature probes to directly measure vial heat transfer coefficients (K) during primary and secondary drying stages of lyophilization. It is observed that K is 40-80% smaller during secondary drying than primary drying, and this value exhibits a weaker dependence on chamber pressure than in primary drying. These observations arise because water vapor in the chamber significantly decreases between primary and secondary drying, which alters the gas conductivity between the shelf and vial. This study tabulates K values for secondary drying for different vials and different chamber pressures, and demarcates the contributions from gas conduction. Lastly, the study performs an energy budget analysis on two different vials (10R glass vial and 10 mL plastic vial) to determine the major factors that contribute to vial energy consumption. During primary drying, the majority of energy supplied goes towards sublimation, while for secondary drying, the majority of energy goes towards heating the vial wall rather than desorbing bound water. We discuss the consequences of this behavior for heat transfer modeling. During secondary drying, the heat of desorption can be neglected in thermal modeling for some materials (e.g., glass) but not others (e.g., plastic vials).
本研究使用热通量传感器和温度探头，在冻干的一次干燥和二次干燥阶段直接测量小瓶的传热系数（K）。据观察，二次干燥期间的K值比一次干燥时小40 - 80%，并且该值对腔室压力的依赖性比一次干燥时弱。出现这些观察结果的原因是，一次干燥和二次干燥之间腔室内的水蒸气显著减少，这改变了搁板和小瓶之间的气体传导率。本研究列出了不同小瓶和不同腔室压力下二次干燥的K值，并划分了气体传导的贡献。最后，该研究对两种不同的小瓶（10R玻璃小瓶和10 mL塑料小瓶）进行了能量平衡分析，以确定导致小瓶能量消耗的主要因素。在一次干燥期间，供应的大部分能量用于升华，而在二次干燥期间，大部分能量用于加热小瓶壁而不是解吸结合水。我们讨论了这种行为对传热建模的影响。在二次干燥期间，对于某些材料（如玻璃），在热建模中可以忽略解吸热，但对于其他材料（如塑料小瓶）则不能忽略。
