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 Feb 23;22(3):82. doi: 10.1208/s12249-021-01953-8.
Current trends in the pharmaceutical industry led to a demand for more flexible manufacturing processes with smaller batch sizes. Prepackaged nested vials that can be processed as a unit were introduced into the market to fulfill this need. However, vial nests provide a different thermal environment for the vials compared to a hexagonal packaging array and could therefore influence product temperature profiles, primary drying times, and product quality attributes. Polymer caps with the possibility of vial closure inside the freeze-drying chamber were developed to remove the risks and need of a crimping process. A general concern with the use of such caps is the possibility of an increase in resistance to water vapor flow out of the vial. This case study investigated the effect of the LyoSeal and PLASCAP polymer caps and EZ-fill nests on the freeze-drying process. Amorphous and partially crystalline model formulations were freeze-dried. Process data and product quality attributes were compared for regularly stoppered vials and vials with polymer caps as well as vials in a hexagonal packaging array and nested vials. The results indicated no increased resistance or impeded water vapor flow by the polymer caps. Differences in the macro- and microscopic appearances of products and a trend towards lower product temperatures were observed for the investigated nest type compared to a regular hexagonal packaging array. Consequently, the polymer caps could be used as an alternative to regular stoppers without affecting freeze-drying process data or product quality attributes, while the different thermal environment of nested vials should be considered.
当前，制药行业的发展趋势要求制造工艺更加灵活，批量更小。为满足这一需求，市场上推出了可作为一个单元进行处理的预包装嵌套小瓶。然而，与六方包装阵列相比，小瓶巢为小瓶提供了不同的热环境，因此可能会影响产品温度曲线、初级干燥时间和产品质量属性。开发了具有在冷冻干燥腔室内对小瓶进行密封可能性的聚合物盖，以消除压接工艺的风险和需求。使用这种盖子的一个普遍关注点是，小瓶内的水蒸气流出阻力可能会增加。本案例研究调查了 LyoSeal 和 PLASCAP 聚合物盖以及 EZ-fill 嵌套小瓶对冷冻干燥过程的影响。对无定形和部分结晶模型制剂进行了冷冻干燥。比较了常规密封小瓶、带有聚合物盖的小瓶以及六方包装阵列中的小瓶和嵌套小瓶的工艺数据和产品质量属性。结果表明，聚合物盖不会增加阻力或阻碍水蒸气的流动。与常规六方包装阵列相比，在所研究的巢式类型中，产品的宏观和微观外观存在差异，且产品温度呈下降趋势。因此，聚合物盖可以替代常规瓶塞使用，而不会影响冷冻干燥工艺数据或产品质量属性，同时应考虑嵌套小瓶的不同热环境。
