Evaluation of factors influencing ampoule secondary particulate contamination. A strategy for its reduction in small volume parenterals.

In this paper, we evaluated the influence of some glass ampoules characteristics that are critical as far as secondary particle contamination (visible and sub-visible) of small volume parenterals. Following characteristics were considered: snap-opening system (colour-break scoring and o.p.c.); break-point strength (high and low); dimensional characteristics (three types D1, D2, D3). According to the proper statistical design, 18 different batches of 2 ml ampoules filled with water for injection were manufactured; then sub-visible and visible particulate contamination generated on snap-opening the ampoules were examined. Sub visible particle counting was performed by the light-blockage method and visible particles counting by the membrane-filtration method. With regard to sub-visible particles, statistical analysis showed significant interactions of break-point strength with both ampoule dimensional characteristics and the type of snap-opening system. Break-point strength seems to have the greatest influence on the level of particulate contamination. Differences in ampoule snap-opening systems and dimensional characteristics exert a significant effect on the level of particle contamination only at high break-point strength. With regard to visible particles generated on snapping the ampoules, data are consistent with the findings of sub-visible particulate contamination. Ampoules manufactured according to DIN dimensional characteristics and with an o.p.c. snap-opening system provide the lowest particle burden.