Time-Dependence of Pressure in Lyophilization Vials

Abstract

Lyophilized pharmaceuticals are often sealed under reduced pressure and "vacuum testing" is done as a part of quality assurance. In this work the pressure P_v inside lyophilization vials was measured as a function of storage time after sealing at a chamber pressure P_c < 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 P_v was observed to rise to ~2 torr within ca. 50 hrs, then increase slowly to P_v = 5–10 torr after the lapse of 2300 hrs (3 months). Calculations based on outgassing and permeation of the stopper by O_2, N₂ 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 P_v 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.