Unraveling Pre-filled Syringe Needle Clogging: Exploring a Fresh Outlook Through Innovative Techniques.

OBJECTIVE: This study aimed to investigate the movement of liquid in the needle region of staked-in-needle pre-filled syringes using neutron imaging and synchrotron X-ray tomography. The objective was to gain insights into the dynamics of liquid presence and understand the factors contributing to needle clogging. METHODS: Staked-in-needle pre-filled syringes were examined using neutron radiography and synchrotron X-ray phase-contrast computed tomography. Neutron radiography provided a 2D visualization of liquid presence in the needle, while synchrotron X-ray tomography offered high-resolution 3D imaging to study detailed morphological features of the liquid. RESULTS: Neutron radiography revealed liquid presence in the needle region for as-received samples and after temperature and pressure cycling. Pressure cycling had a more pronounced effect on liquid formation. Synchrotron X-ray tomography confirmed the presence of liquid and revealed various morphologies, including droplets of different sizes, liquid segments blocking sections of the needle, and a thin layer covering the needle wall. Liquid presence was also observed between the steel needle and the glass barrel. CONCLUSIONS: The combination of neutron imaging and synchrotron X-ray tomography provided valuable insights into the dynamics of liquid movement in staked-in-needle pre-filled syringes. Temperature and pressure cycling were found to contribute to additional liquid formation, with pressure changes playing a significant role. The detailed morphological analysis enhanced the understanding of microstructural arrangements within the needle. This research contributes to addressing the issue of needle clogging and can guide the development of strategies to improve pre-filled syringe performance.

Design of a Reciprocal Injection Device for Stability Studies of Parenteral Biological Drug Products.

Formulation screening, essential for assessing the impact of physical, chemical, and mechanical stresses on protein stability, plays a critical role in biologics drug product development. This research introduces a Reciprocal Injection Device (RID) designed to accelerate formulation screening by probing protein stability under intensified stress conditions within prefilled syringes. This versatile device is designed to accommodate a broad spectrum of injection parameters and diverse syringe dimensions. A commercial drug product was employed as a model monoclonal antibody formulation. Our findings effectively highlight the efficacy of the RID in assessing concentration-dependent protein stability. This device exhibits significant potential to amplify the influences of interfacial interactions, such as those with buffer salts, excipients, air, metals, and silicone oils, commonly found in combination drug products, and to evaluate the protein stability under varied stresses.