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.
Drug Product Science and Technology, Pharmaceutical Development, Research and Development, Bristol-Myers Squibb, New Brunswick, New Jersey, 08903, USA. Songyan.zheng@bms.com.
Songyan
S
Zheng
Drug Product Science and Technology, Pharmaceutical Development, Research and Development, Bristol-Myers Squibb, New Brunswick, New Jersey, 08903, USA.
Aastha
A
Puri
Drug Product Science and Technology, Pharmaceutical Development, Research and Development, Bristol-Myers Squibb, New Brunswick, New Jersey, 08903, USA.
Jinjiang
J
Li
Biolin Scientific Inc, 215 College Road, Suite 300, Paramus, New Jersey, 07652, USA.
Archana
A
Jaiswal
Drug Product Science and Technology, Pharmaceutical Development, Research and Development, Bristol-Myers Squibb, New Brunswick, New Jersey, 08903, USA.
Monica
M
Adams
D004349:Drug Packaging; D007091:Image Processing, Computer-Assisted; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011136:Polysorbates / Q000737:chemistry; D055550:Protein Stability; D011791:Quartz / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry*; D012827:Silicone Oils / Q000737:chemistry*; D012995:Solubility; D013499:Surface Properties; D013594:Syringes
D004364:Pharmaceutical Preparations; D011136:Polysorbates; D011994:Recombinant Proteins; D012827:Silicone Oils; D011791:Quartz
Archimedes; micro-flow imaging (MFI); pre-filled syringe; protein particles; quartz crystal microbalance with dissipation (QCM-D); silicone oil particles