Stopper Movement and Headspace (Air Bubble Size) Limitations for 2.25 mL Prefilled Syringe.

The sterile barrier is one of the most important aspects of the container closure integrity (CCI) for a prefilled syringe (PFS or syringe). This crucial barrier enables the protection of the syringe contents from contamination. The plunger stopper (stopper) is naturally in a stationary position that is controlled by the static friction between the plunger stopper and the syringe barrel wall. When an applied force is greater than the static friction, which is commonly known as the break-loose force, the plunger stopper will move. In such conditions, the stopper movement can further be increased if an air bubble (AB) is introduced between the liquid fill in the syringe and the stopper during the stoppering process. This additional movement can occur when the pressure differential between the gaseous headspace inside the syringe and the external atmosphere is large enough that the force exerted on the stopper exceeds the break-loose force of the syringe. This can occur during altitude or temperature changes incurred during aerial or mountainous transport. This article, therefore, discusses the relationship between stopper movement and initial headspace (air bubble size/ABS) in a 2.25 mL Type I glass syringe using theoretical and empirical approaches. The results showed the maximum initial headspace needed to enable CCI at specified altitudes and plunger stopper movements for the syringe-plunger stopper combination used in the study. Empirical data also indicated that CCI can be maintained for this syringe-plunger stopper combination with up to 9.0 mm initial headspace at altitudes up to 17,000 feet.