Time-dependence of pressure in lyophilization vials.

Lyophilized pharmaceuticals are often sealed under reduced pressure and "vacuum testing" is done as a part of quality assurance. In this work the pressure Pv inside lyophilization vials was measured as a function of storage time after sealing at a chamber pressure Pc < 20 mtorr. Vials were of 50 mL nominal capacity (empty and with product) and 10 mL nominal capacity (with product). For all three sample types Pv was observed to rise to approximately 2 torr within ca. 50 hrs, then increase slowly to Pv = 5-10 torr after the lapse of 2300 hrs (3 months). Calculations based on outgassing and permeation of the stopper by O2, NH2 and H2O demonstrate that vial pressure is primarily due to desorption of water vapor from the stopper into the headspace of the vial. The presence of a hydrophilic product decreases the rate of pressure rise, and Pv increases more rapidly in smaller vials. Results are discussed in terms of testing for seal integrity and for stopper effects on moisture in the product.