PT  - JOURNAL ARTICLE
AU  - Liang Fang
AU  - Galen Huaiqiu Shi
AU  - Coralie ADÈle Richard
AU  - Xia Dong
AU  - Justin C. Thomas
AU  - Michael C. Victor
AU  - Tingting Wang
AU  - Sharon Shinkle
AU  - Cathy Zhao
TI  - Drug Formulation Impact on Prefilled Syringe Functionality and Autoinjector Performance
AID  - 10.5731/pdajpst.2020.011627
DP  - 2020 Nov 01
TA  - PDA Journal of Pharmaceutical Science and Technology
PG  - 674--687
VI  - 74
IP  - 6
4099  - http://journal.pda.org/content/74/6/674.short
4100  - http://journal.pda.org/content/74/6/674.full
SO  - PDA J Pharm Sci Technol2020 Nov 01; 74
AB  - 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.