Chan Edwin, Hubbard Aaron, Sane Samir, Maa Yuh-Fun
Pharmaceutical Processing and Technology Development, Genentech, a member of Roche Group.
PDA J Pharm Sci Technol. 2012 Mar-Apr;66(2):136-50. doi: 10.5731/pdajpst.2012.00856.
The interior barrel of the prefilled syringe is often lubricated/siliconized by the syringe supplier or at the syringe filling site. Syringe siliconization is a complex process demanding automation with a high degree of precision; this information is often deemed "know-how" and is rarely published. The purpose of this study is to give a detailed account of developing and optimizing a bench-top siliconization unit with nozzle diving capabilities. This unit comprises a liquid dispense pump unit and a nozzle integrated with a Robo-cylinder linear actuator. The amount of coated silicone was determined by weighing the syringe before and after siliconization, and silicone distribution was visually inspected by glass powder coating or characterized by glide force testing. Nozzle spray range, nozzle retraction speed, silicone-coated amount, and air-to-nozzle pressure were found to be the key parameters affecting silicone distribution uniformity. Distribution uniformity is particularly sensitive to low-target silicone amount where the lack of silicone coating on the barrel near the needle side often caused the syringes to fail the glide force test or stall when using an autoinjector. In this bench-top unit we identified optimum coating conditions for a low silicone dose, which were also applicable to a pilot-scale siliconization system. The pilot unit outperformed the bench-top unit in a tighter control (standard deviation) in coated silicone amount due to the elimination of tubing flex. Tubing flex caused random nozzle mis-sprays and was prominent in the bench-top unit, while the inherent design of the pilot system substantially limited tubing flux. In summary, this bench-top coating unit demonstrated successful siliconization of the 1 mL long syringe with ∼0.2 mg of silicone oil using a spraying cycle also applicable to larger-scale siliconization.
Syringe siliconization can be considered a well-established manufacturing process and has been implemented by numerous syringe providers. However, its technical details and associated critical process parameters are rarely published. The purpose of this study is three-fold: (1) to reveal design details of a bench-top siliconization unit, (2) to identify critical process parameters and determine their optimum range to provide consistent and even silicone coating, and (3) to demonstrate the applicability of the optimum process condition derived from the bench-top unit to a pilot siliconization unit. The outcomes of this study will benefit scientists and engineers developing pre-filled syringe products by helping them to better understanding silicone spray coating principles and their relationship to siliconization processes in a large-scale manufacturing setting.
预填充注射器的内筒通常由注射器供应商或在注射器灌装现场进行润滑/硅化处理。注射器硅化是一个复杂的过程，需要高精度的自动化；此信息通常被视为“专有技术”，很少有相关报道。本研究的目的是详细介绍一种具有喷嘴潜入功能的台式硅化装置的开发和优化过程。该装置包括一个液体分配泵单元和一个与机器人气缸线性致动器集成的喷嘴。通过对硅化前后的注射器进行称重来确定涂覆的硅酮量，并通过玻璃粉末涂层目视检查硅酮分布情况，或通过滑动力测试对其进行表征。发现喷嘴喷雾范围、喷嘴缩回速度、硅酮涂覆量和空气与喷嘴压力是影响硅酮分布均匀性的关键参数。分布均匀性对低目标硅酮量特别敏感，在针侧附近的针筒上缺乏硅酮涂层时，通常会导致注射器在使用自动注射器时滑动力测试失败或堵塞。在这个台式装置中，我们确定了低硅酮剂量的最佳涂覆条件，这些条件也适用于中试规模的硅化系统。由于消除了管路弯曲，中试装置在涂覆硅酮量的更严格控制（标准偏差）方面优于台式装置。管路弯曲会导致喷嘴随机误喷，在台式装置中很明显，而中试系统的固有设计大大限制了管路通量。总之，这个台式涂覆装置使用适用于更大规模硅化的喷雾循环，成功地对1 mL长的注射器进行了硅化处理，硅酮油用量约为0.2 mg。
注射器硅化可被视为一种成熟的制造工艺，许多注射器供应商都已采用。然而，其技术细节和相关的关键工艺参数很少有报道。本研究的目的有三个：（1）揭示台式硅化装置的设计细节，（2）确定关键工艺参数并确定其最佳范围，以提供一致且均匀的硅酮涂层，（3）证明从台式装置得出的最佳工艺条件对中试硅化装置的适用性。本研究的结果将有助于开发预填充注射器产品的科学家和工程师更好地理解硅酮喷雾涂层原理及其在大规模制造环境中与硅化过程的关系。
