Department of Pharmaceutics, Freeze Drying Focus Group (FDFG), Friedrich-Alexander University (FAU) Erlangen-Nuremberg, Cauerstrasse 4, 91058, Erlangen, Germany.
GILYOS GmbH|, Friedrich-Bergius-Ring 15, 97076, Würzburg, Germany.
AAPS PharmSciTech. 2021 Jan 27;22(2):57. doi: 10.1208/s12249-021-01926-x.
Recent advances in molded vial manufacturing enabled manufacturers to use a new manufacturing technique to achieve superior homogeneity of the vial wall thickness. This study evaluated the influence of the different manufacturing techniques of molded vials and glass compositions on vial heat transfer in freeze-drying. Additionally, the influence of using empty vials as thermal shielding on thermal characteristics of edge and center vials was investigated. The vial heat transfer coefficient K was determined gravimetrically for multiple vial systems. The results showed superior heat transfer characteristics of the novel manufacturing technique as well as differences in heat transfer for the different glass compositions. Empty vials on the outside of the array did not influence center vial K values compared to a full array. The direct contact area and vial bottom curvature and their correlation to heat transfer parameters were analyzed across multiple vial systems. A new approach based on light microscopy to describe the vial bottom curvature more accurately was described. The presented results for the contact area allowed for an approximation of the pressure-independent heat transfer parameter KC. The results for the vial bottom curvature showed a great correlation to the pressure-dependent heat transfer parameter KD. Overall, the results highlighted how a thorough geometrical characterization of vials with known heat transfer characteristics could be used to predict thermal characteristics of new vial systems as an alternative to a time-consuming gravimetric K determination. Primary drying times were simulated to show the influence of K on drying performance.
最近，模制小瓶制造方面的进展使制造商能够使用新的制造技术来实现小瓶壁厚度更优越的均一性。本研究评估了模制小瓶和玻璃成分的不同制造技术对冷冻干燥中小瓶传热的影响。此外，还研究了使用空小瓶作为热屏蔽对边缘和中心小瓶热特性的影响。通过重量法确定了多个小瓶系统的小瓶传热系数 K。结果表明，新型制造技术具有优越的传热特性，并且不同的玻璃成分在传热方面存在差异。与装满小瓶的阵列相比，外部的空小瓶对中心小瓶的 K 值没有影响。分析了多个小瓶系统的直接接触面积以及小瓶底部曲率及其与传热参数的相关性。描述了一种基于光学显微镜的新方法，可以更准确地描述小瓶底部曲率。所得到的接触面积结果允许对与压力无关的传热参数 KC 进行近似。小瓶底部曲率的结果与与压力相关的传热参数 KD 具有很好的相关性。总的来说，研究结果强调了如何使用具有已知传热特性的小瓶的全面几何特性来预测新小瓶系统的热特性，这是一种替代耗时的重量法 K 确定的方法。模拟了初步干燥时间以显示 K 对干燥性能的影响。
