Abstract
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.
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Acknowledgments
The authors thank Drs. Munir Hussain, Nancy Barbour, and Otilia Koo for reviewing this manuscript; Dr. Rajesh Gandhi for supporting this study; and Dr Arnold Luk for supporting QCM-D data collection.
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Guest Editors: Otilia M. Koo, Panayiotis P. Constantinides, Lavinia M. Lewis, and Joseph Reo
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Zheng, S., Puri, A., Li, J. et al. Particle Characterization for a Protein Drug Product Stored in Pre-Filled Syringes Using Micro-Flow Imaging, Archimedes, and Quartz Crystal Microbalance with Dissipation. AAPS J 19, 110–116 (2017). https://doi.org/10.1208/s12248-016-9983-1
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DOI: https://doi.org/10.1208/s12248-016-9983-1