Physicochemical Excipient-Container Interactions in Prefilled Syringes and Their Impact on Syringe Functionality.

Previous studies have shown that parenteral formulation excipients can interact with the silicone oil in prefilled syringes, thereby causing variations in glide force that affect the performance of autoinjectors. Thus, it is crucial to control the glide force of the prefilled syringes to mitigate the potential risk of dose inaccuracies. This study provided a systematic understanding of the chemical interactions between the excipients, physical interactions between the excipients and the container, as well as their impact on the functional performance of prefilled syringes. The design of experiment approach used in this study generated statistically meaningful data, which confirmed that different excipients caused varying increase in glide force in siliconized prefilled syringes. The data indicated that poloxamer 188 can more effectively maintain stable glide forces during accelerated storage conditions compared with polysorbate 80. This finding was further enhanced using Hansen solubility parameters theory, which provided a fundamental understanding of the mechanisms behind the physical interactions. Chemical stability analysis of the surfactants suggested that degradation of excipients also impacts syringe functionality. In summary, the results revealed the unique interactions between parenteral pharmaceutical excipients and primary packaging systems and the physicochemical foundation behind them.

Drug Formulation Impact on Prefilled Syringe Functionality and Autoinjector Performance.

Given the surging interest in developing prefilled syringe and autoinjector combination products, investment in an early compatibility assessment is critical to prevent unwarranted drug/container closure interactions and avoid potential reformulation during late stages of drug development. In addition to the standard evaluation of drug stability, it is important to consider container closure functionality and overall device performance changes over time because of drug-container closure component interaction. This study elucidated the mechanisms that cause changes in syringe glide force over time and the impact on the injection duration. It was an expansion of the previous work, which indicated that drug formulation variables such as formulation excipients and pH affect syringe functionality over time. The current study described an investigative process for troubleshooting prolonged and variable autoinjector injection time caused by an increased syringe glide force variability over time. This increase in glide force variability stems from two root causes, namely plunger dimensional variation and syringe silicone oil change over time. The results demonstrated (a) the underlying factors of silicone oil change in the presence of drug formulation matrices, (b) accelerated stability of syringe glide force as a good indicator of long-term, real-time stability, and (c) that buffer matrix-filled syringes can be used to predict the syringe functionality and stability of drug product-filled syringes. Based on the experimental findings of a variety of orthogonal characterization techniques including contact angle, interfacial tension, and calculation of Hansen solubility parameters, it is proposed that silicone oil change is caused by formulation excipients and a complex set of phenomena summarized as "wet, wash, and delube" processes.