PT  - JOURNAL ARTICLE
AU  - Gehrmann, Matthew R
AU  - McAndrew, T Page
TI  - Long-Term Study of Container Closure Integrity of Rubber-Glass Vial Systems by Multiple Methods
AID  - 10.5731/pdajpst.2019.010223
DP  - 2019 Jan 01
TA  - PDA Journal of Pharmaceutical Science and Technology
PG  - pdajpst.2019.010223
4099  - http://journal.pda.org/content/early/2019/08/16/pdajpst.2019.010223.short
4100  - http://journal.pda.org/content/early/2019/08/16/pdajpst.2019.010223.full
AB  - A one-year study to establish the container closure integrity (CCI) performance landscape of systems comprising rubber stoppers and glass vials was performed. Focus was addressing the issues of CCI performance versus: (a) time, (b) compression levels and residual seal force (RSF) values, and (c) potential variation in results based upon deterministic measurement method (tracer gas and frequency modulated spectroscopy). To reduce sample size to a manageable number, the study was based upon a design of experiments that considered a range of: (a) stopper formulations, sizes, and configurations; (b) vial sizes, types, and suppliers; (c) compression levels. All systems showed good performance; there was no decrease in CCI with time − highlighting the general robustness of rubber-glass vial systems. Lower compression/RSF values tended to give slightly lower performance and wider scatter in data, and thus should not be recommended for commercial applications. A small amount of oxygen exchange through stoppers was observed for all systems − to be expected since rubber is known to be gas permeable. RSF values decreased initially, then remained constant − consistent with models. Results are consistent with literature.