Siliconized stoppers, when used with parenteral drug products, have been shown to be a source of particulate contamination. In this study, five different variables: pH of the solution, buffer concentration, Teflon coating on the stopper, autoclaving cycle (F0), and lot-to-lot variation of the siliconization process were evaluated using an eight-run Plackett-Burman design with respect to their impact on the level of particulate contamination from siliconized stoppers. Results show that pH of the solution can significantly affect the particulate level of samples using siliconized stoppers (p < 0.05). An alkaline solution (pH = 8) was shown to produce a higher particulate load than an acid solution (pH = 4). The main effect of the remaining four variables was determined to be statistically insignificant (p > 0.15).