Particle Characterization for a Protein Drug Product Stored in Pre-Filled Syringes Using Micro-Flow Imaging, Archimedes, and Quartz Crystal Microbalance with Dissipation.
Micro-flow imaging (MFI) has been used for formulation development for analyzing sub-visible particles. Archimedes, a novel technique for analyzing sub-micron particles, has been considered as an orthogonal method to currently existing techniques. This study utilized these two techniques to investigate the effectiveness of polysorbate (PS-80) in mitigating the particle formation of a therapeutic protein formulation stored in silicone oil-coated pre-filled syringes. The results indicated that PS-80 prevented the formation of both protein and silicone oil particles. In the case of protein particles, PS-80 might involve in the interactions with the hydrophobic patches of protein, air bubbles, and the stressed surfaces of silicone oil-coated pre-filled syringes. Such interactions played a role in mitigating the formation of protein particles. Subsequently, quartz crystal microbalance with dissipation (QCM-D) was utilized to characterize the interactions associated with silicone oil, protein, and PS-80 in the solutions. Based on QCM-D results, we proposed that PS-80 likely formed a layer on the interior surfaces of syringes. As a result, the adsorbed PS-80 might block the leakage of silicone oil from the surfaces to solution so that the silicone oil particles were mitigated at the presence of PS-80. Overall, this study demonstrated the necessary of utilizing these three techniques cooperatively in order to better understand the interfacial role of PS-80 in mitigating the formation of protein and silicone oil particles.
['Zheng|Songyan|S|', 'Puri|Aastha|A|', 'Li|Jinjiang|J|', 'Jaiswal|Archana|A|', 'Adams|Monica|M|']
D004349:Drug Packaging D007091:Image Processing, Computer-Assisted D010316:Particle Size D004364:Pharmaceutical Preparations D011136:Polysorbates D055550:Protein Stability D011791:Quartz D011994:Recombinant Proteins D012827:Silicone Oils D012995:Solubility D013499:Surface Properties D013594:Syringes
pre-filled syringe Archimedes micro-flow imaging (MFI) silicone oil particles protein particles quartz crystal microbalance with dissipation (QCM-D)