Werk T, Ludwig I S, Luemkemann J, Huwyler J, Mahler H-C, Haeuser C R, Hafner M
Pharmaceutical Technology, University of Basel, Basel, Switzerland; Pharmaceutical Development & Supplies, F. Hoffmann-La Roche Ltd., Basel, Switzerland; currently at Lonza AG, Drug Product Services, Basel, Switzerland; and Institute for Medical Technology, Heidelberg University and Mannheim University of Applied Sciences, Mannheim (Germany)
Pharmaceutical Development & Supplies, F. Hoffmann-La Roche Ltd., Basel, Switzerland; currently at Lonza AG, Drug Product Services, Basel, Switzerland; and.
PDA J Pharm Sci Technol. 2016 May-Jun;70(3):191-207. doi: 10.5731/pdajpst.2015.006155. Epub 2016 Feb 9.
Dual-chamber systems can offer self-administration and home care use for lyophilized biologics. Only a few products have been launched in dual-chamber systems so far-presumably due to dual-chamber systems' complex and costly drug product manufacturing process. Within this paper, two improved processes (both based on tray filling technology) for freeze-drying pharmaceuticals in dual-chamber systems are described. Challenges with regards to heat transfer were tackled by (1) performing the freeze-drying step in a needle-down orientation in combination with an aluminum block, or (2) freeze-drying the drug product "externally" in a metal cartridge with subsequent filling of the lyophilized cake into the dual-chamber system. Metal-mediated heat transfer was shown to be efficient in both cases and batch (unit-to-unit) homogeneity with regards to sublimation rate was increased. It was difficult to influence ice crystal size using different methods when in use with an aluminum block due to its heat capacity. Using such a metal carrier implies a large heat capacity leading to relatively small ice crystals. Compared to the established process, drying times were reduced by half using the new processes. The drying time was, however, longer for syringes compared to vials due to the syringe design (long and slim). The differences in drying times were less pronounced for aggressive drying cycles. The proposed processes may help to considerably decrease investment costs into dual-chamber system fill-finish equipment.
Dual-chamber syringes offer self-administration and home care use for freeze-dried pharmaceuticals. Only a few products have been launched in dual-chamber syringes so far-presumably due to their complex and costly drug product manufacturing process. In this paper two improved processes for freeze-drying pharmaceuticals in dual-chamber syringes are described. The major challenge of freeze-drying is to transfer heat through a vacuum. The proposed processes cope with this challenge by (1) freeze-drying the drug product in the syringe in an orientation in which the product is closest to the heat source, or (2) freeze-drying the drug product outside the syringe in a metal tube. The latter requires filling the freeze-dried product subsequently into the dual-chamber syringe. Both processes were very efficient and promised to achieve similar freeze-drying conditions for all dual-chamber syringes within one production run. The proposed processes may help to considerably decrease investment costs into dual-chamber syringe fill-finish equipment.
双腔系统可为冻干生物制品提供自我给药和家庭护理用途。到目前为止，只有少数产品采用双腔系统推出，这可能是由于双腔系统复杂且昂贵的药品制造工艺。在本文中，描述了两种用于双腔系统中冻干药物的改进工艺（均基于托盘灌装技术）。关于传热的挑战通过以下方式解决：（1）以针头向下的方向结合铝块进行冻干步骤，或（2）在金属药筒中“外部”冻干药品，随后将冻干饼填充到双腔系统中。在这两种情况下，金属介导的传热都被证明是有效的，并且升华速率方面的批次（单位间）均匀性得到了提高。使用铝块时，由于其热容量，很难用不同方法影响冰晶大小。使用这种金属载体意味着热容量大，导致冰晶相对较小。与既定工艺相比，新工艺使干燥时间减少了一半。然而，由于注射器的设计（长而细），注射器的干燥时间比小瓶更长。对于激进的干燥周期，干燥时间的差异不太明显。所提出的工艺可能有助于大幅降低双腔系统灌装和灭菌设备的投资成本。
双腔注射器可为冻干药品提供自我给药和家庭护理用途。到目前为止，只有少数产品采用双腔注射器推出，这可能是由于其复杂且昂贵的药品制造工艺。本文描述了两种用于双腔注射器中冻干药品的改进工艺。冻干的主要挑战是通过真空传递热量。所提出的工艺通过以下方式应对这一挑战：（1）在注射器中以产品最接近热源的方向冻干药品，或（2）在金属管中在注射器外部冻干药品。后者需要随后将冻干产品填充到双腔注射器中。这两种工艺都非常有效，并有望在一次生产运行中为所有双腔注射器实现相似的冻干条件。所提出的工艺可能有助于大幅降低双腔注射器灌装和灭菌设备的投资成本。
