Effect of the design of the stopper including dimension, type, and vent area on lyophilization process.

The objective of this study was to investigate if the dimension and the design of stoppers may affect the moisture vapor transfer rate during the lyophilization process. The rate of vapor transfer across the vent, the temperature of the frozen product, and the vapor pressure inside the vial were monitored during the early primary drying phase in vials that were fitted with specially designed Teflon discs with circular holes (area ranging from 0.12 to 41.80 mm(2)) instead of stoppers. It was observed that although the rate of vapor transfer from the vial increased with the cross-sectional area of the vent, the increase tapered off as the area of the vent approached approximately 6 mm(2) in the case when the shelf temperature was at 0 °C and 10 mm(2) in the case when the shelf temperature was at 25 °C. Despite the higher accumulated pressure inside the vial and the corresponding higher temperatures of the frozen product, the rate of water vapor transfer across the vents was lower at the smaller vents, suggesting that the vapor transfer flow regime was under the choked conditions. Studies with various stopper configurations (1-leg, 2-leg, and 3-leg) and vent areas also showed that as long as the vent areas are greater than the critical mass transfer restriction threshold then there should not be any difference in the overall drying behavior and that substitution of stoppers within the range should yield similar drying cycles.